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1.
Front Immunol ; 15: 1398508, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38983860

RESUMO

Background: CD38 and CD47 are expressed in many hematologic malignancies, including multiple myeloma (MM), B-cell non-Hodgkin lymphoma (NHL), B-cell acute lymphoblastic leukemia (ALL), and B-cell chronic lymphocytic leukemia (CLL). Here, we evaluated the antitumor activities of CD38/CD47 bispecific antibodies (BsAbs). Methods: Five suitable anti-CD38 antibodies for co-targeting CD47 and CD38 BsAb were developed using a 2 + 2 "mAb-trap" platform. The activity characteristics of the CD38/CD47 BsAbs were evaluated using in vitro and in vivo systems. Results: Using hybridoma screening technology, we obtained nine suitable anti-CD38 antibodies. All anti-CD38 antibodies bind to CD38+ tumor cells and kill tumor cells via antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Five anti-CD38 antibodies (4A8, 12C10, 26B4, 35G5, and 65A7) were selected for designing CD38/CD47 BsAbs (IMM5605) using a "mAb-trap" platform. BsAbs had higher affinity and binding activity to the CD38 target than those to the CD47 target, decreasing the potential on-target potential and off-tumor effects. The CD38/CD47 BsAbs did not bind to RBCs and did not induce RBC agglutination; thus, BsAbs had much lower blood toxicity. The CD38/CD47 BsAbs had a greater ability to block the CD47/SIRPα signal in CD38+/CD47+ tumor cells than IMM01 (SIRPα Fc fusion protein). Through Fc domain engineering, CD38/CD47 BsAbs were shown to kill tumors more effectively by inducing ADCC and ADCP. IMM5605-26B4 had the strongest inhibitory effect on cellular CD38 enzymatic activity. IMM5605-12C10 had the strongest ability to directly induce the apoptosis of tumor cells. The anti-CD38 antibody 26B4 combined with the SIRPα-Fc fusion proteins showed strong antitumor effects, which were better than any of the mono-therapeutic agents used alone in the NCI-H929 cell xenograft model. The CD38/CD47 BsAbs exhibited strong antitumor effects; specifically, IMM5605-12C10 efficiently eradicated all established tumors in all mice. Conclusion: A panel of BsAbs targeting CD38 and CD47 developed based on the "mAb-tarp" platform showed potent tumor-killing ability in vitro and in vivo. As BsAbs had lower affinity for binding to CD47, higher affinity for binding to CD38, no affinity for binding to RBCs, and did not induce RBC agglutination, we concluded that CD38/CD47 BsAbs are safe and have a satisfactory tolerability profile.


Assuntos
ADP-Ribosil Ciclase 1 , Antígeno CD47 , Neoplasias Hematológicas , Antígeno CD47/imunologia , Antígeno CD47/antagonistas & inibidores , Antígeno CD47/metabolismo , ADP-Ribosil Ciclase 1/antagonistas & inibidores , ADP-Ribosil Ciclase 1/imunologia , ADP-Ribosil Ciclase 1/metabolismo , Humanos , Animais , Camundongos , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/imunologia , Linhagem Celular Tumoral , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto , Glicoproteínas de Membrana/imunologia , Glicoproteínas de Membrana/antagonistas & inibidores , Citotoxicidade Celular Dependente de Anticorpos , Feminino , Antineoplásicos Imunológicos/farmacologia
3.
Pediatr Blood Cancer ; : e31198, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39016596

RESUMO

OBJECTIVE: With the evolution of data algorithms and personalized push systems in mobile applications, patients who have searched for disease-related information may repeatedly receive similar content on app homepages or through notifications. This study aims to assess the influence of health-related content delivered through mobile applications on the anxiety and depression levels of caregivers of pediatric oncology patients. METHODS: A survey consisting of 16 questions was conducted among 91 caregivers of pediatric oncology patients at the Children's Hospital affiliated with Chongqing Medical University. The questionnaire was designed by oncologists and the Hospital Anxiety and Depression Scale was used to assess the caregivers' psychological states. RESULTS: The study found that 31.5% of caregivers exhibited borderline anxiety symptoms, while 20.2% displayed borderline depression symptoms. Caregivers who noticed changes in homepage recommendations reported higher levels of anxiety (p = .004) and depression (p = .034). Additionally, 50.6% occasionally felt anxious or uneasy due to personalized notifications and 19.1% frequently felt this way. Moreover, 53.9% of the caregivers reported a negative impact on their emotions or daily life. SIGNIFICANCE: Personalized push notifications related to disease information in mobile applications can impose a significant psychological burden on patients and their caregivers. Mobile application developers and healthcare providers must strengthen their support in the digital health domain to enhance the emotional well-being of cancer patients and their caregivers.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38923559

RESUMO

BACKGROUND AND AIMS: For chronic hepatitis B (CHB) patients, there is still a need to improve hepatitis B surface antigen (HBsAg) clearance rates. This study aimed to assess the predictive effectiveness of soluble programmed cell death-1 (sPD-1) and soluble programmed cell death ligand-1 (sPD-L1) for HBsAg clearance in HBeAg-negative CHB patients undergoing peginterferon (Peg-IFN)-based antiviral treatment. METHODS: This study encompassed 280 patients undergoing treatment with Peg-IFNα. Serum levels of sPD-1 and sPD-L1 were measured using ELISA kits at baseline, as well as at 12, 24 and 48 weeks. The primary endpoint of the study was the determination of HBsAg clearance at 48 weeks. Logistic regression analysis was employed to identify predictors of HBsAg clearance. RESULTS: The clearance group demonstrated significantly lower serum sPD-L1 levels compared to the non-clearance group. While both groups exhibited an increase in sPD-1 levels, only the clearance group showed a rise in sPD-L1 levels. Multivariate analysis identified sPD-L1 increase at 24 weeks, and HBsAg decline at 24 weeks as predictors for HBsAg clearance at 48 weeks. The combined use of these indicators showed a predictive performance for HBsAg clearance with an AUROC of 0.907 (95% CI: 0.861-0.953, p < 0.001). CONCLUSIONS: The study revealed an inverse relationship between the trends of sPD-1/sPD-L1 and HBsAg clearance during combined IFN and NAs treatment. Moreover, the magnitude of HBsAg reduction and sPD-L1 increase emerged as significant predictors for HBsAg clearance.

6.
Adv Sci (Weinh) ; : e2402551, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38923875

RESUMO

Mounting clinical evidence suggests that a comprised intestinal barrier contributes to the progression of nonalcoholic steatohepatitis (NASH); nevertheless, the precise mechanism remains elusive. This study unveils a significant upregulation of nuclear receptor-binding SET domain protein 2 (NSD2) in the intestines of obese humans and mice subjected to a high-fat cholesterol diet (HFCD). Intestine-specific NSD2 knockout attenuated the progression of intestinal barrier impairment and NASH, whereas NSD2 overexpression exacerbated this progression. Mechanistically, NSD2 directly regulates the transcriptional activation of Ern1 by demethylating histone H3 at lysine 36 (H3K36me2), thus activating the ERN1-JNK axis to intensify intestinal barrier impairment and subsequently foster NASH progression. These findings elucidate the crucial role of NSD2-mediated H3K36me2 in intestinal barrier impairment, suggesting that targeting intestinal NSD2 can represent a novel therapeutic approach for NASH.

7.
PLoS One ; 19(6): e0304591, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38843259

RESUMO

OBJECTIVE: The systemic immuno-inflammatory index (SII), a novel immune marker of inflammation, has not been previously associated with endometriosis. The objective of this research is to explore the link between SII and the occurrence of endometriosis. METHODS: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2001 to 2006, we screened and extracted relevant information from the population. Participants missing data on either SII or endometriosis were excluded. We divided the remaining cohort into quartiles based on SII levels: Q1 (SII < 249, n = 848), Q2 (249 ≤ SII < 604.55, n = 847), Q3 (604.55 ≤ SII < 825.35, n = 847), and Q4 (SII ≥ 852.35, n = 848). Multiple linear regression and smooth curve fitting techniques, were to evaluate the non-linear association between SII and endometriosis. RESULTS: The study included 3,390 adults aged 20 to 55. Multiple linear regression analysis revealed a significant positive correlation between SII and endometriosis [3.14, 95% CI (2.22, 4.45), P < 0.01]. This correlation was consistent across subgroups defined by marital status, poverty income ratio, BMI, alcohol consumption, and age at first menstrual period. However, the relationship between SII and endometriosis was significantly modified by age, education, and history of pregnancy in the stratified analyses. The curve fitting indicated an S-shaped curve, with an inflection point at SII = 1105.76. CONCLUSION: The SII may serve as a predictive marker for endometriosis risk among women in the United States, offering a potentially simple and cost-effective approach. However, given the cross-sectional design of this investigation, further validation in prospective studies is necessary.


Assuntos
Biomarcadores , Endometriose , Inflamação , Inquéritos Nutricionais , Humanos , Endometriose/imunologia , Endometriose/epidemiologia , Feminino , Adulto , Estudos Transversais , Pessoa de Meia-Idade , Adulto Jovem , Estados Unidos/epidemiologia
8.
Nat Med ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38942993

RESUMO

Immunotherapy combined with chemotherapy regimen has been shown to be effective in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). However, due to the small number of patients, its efficacy remains controversial in Asian populations, particularly in mainland China. Here a randomized, double-blind phase 3 trial evaluated the efficacy and safety of finotonlimab (SCT-I10A), a programmed cell death 1 (PD-1) monoclonal antibody, combined with cisplatin plus 5-fluorouracil (C5F) for the first-line treatment of R/M HNSCC. Eligible patients (n = 370) were randomly 2:1 assigned to receive finotonlimab plus C5F (n = 247) or placebo plus C5F (n = 123). The primary endpoint was overall survival (OS). In the finotonlimab plus C5F group, OS was 14.1 months (95% confidence interval (CI) 11.1-16.4), compared with 10.5 months (95% CI 8.1-11.8) in the placebo plus C5F group. The hazard ratio was 0.73 (95% CI 0.57-0.95, P = 0.0165), meeting the predefined superiority criteria for the primary endpoint. Finotonlimab plus C5F showed significant OS superiority compared with C5F alone and acceptable safety profile with R/M HNSCC, supporting its use as a first-line treatment option for R/M HNSCC. These results validate the efficacy and safety of the combination of finotonlimab and C5F in Asian patients with R/M HNSCC. ClinicalTrials.gov identifier: NCT04146402 .

9.
BMC Med Genomics ; 17(1): 159, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867275

RESUMO

BACKGROUND: Association between glucose and inflammatory bowel disease (IBD) was found in previous observational studies and in cohort studies. However, it is not clear whether these associations reflect causality. Thus, this study investigated whether there is such a causal relation between elevated glucose and IBD, Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We performed a two-sample Mendelian Randomization (MR) with the independent genetic instruments identified from the largest available genome-wide association study (GWAS) for IBD (5,673 cases; 213,119 controls) and its main subtypes, CD and UC. Summarized data for glucose which included 200,622 cases and glycemic traits including HbA1c and type 2 diabetes(T2DM) were obtained from different GWAS studies. Primary and secondary analyses were conducted by preferentially using the radial inverse-variance weighted (IVW) approach. A number of other meta-analysis approach and sensitivity analyses were carried out to assess the robustness of the results. RESULTS: We did not find a causal effect of genetically predicted glucose on IBD as a whole (OR 0.858; 95% CI 0.649-1.135; P = 0.286). In subtype analyses glucose was also suggestively not associated with Crohn's disease (OR 0.22; 95% CI 0.04-1.00; P = 0.05) and ulcerative colitis (OR 0.940; 95% CI 0.628-1.407; P = 0.762). In the other direction, IBD and its subtypes were not related to glucose and glycemic traits. CONCLUSIONS: This MR study is not providing any evidence for a causal relationship between genetically predicted elevated glucose and IBD as well as it's subtypes UC and CD. Regarding the other direction, no causal associations could be found. Future studies with robust genetic instruments are needed to confirm this conclusion.


Assuntos
Estudo de Associação Genômica Ampla , Doenças Inflamatórias Intestinais , Análise da Randomização Mendeliana , Humanos , Doenças Inflamatórias Intestinais/genética , Glicemia , Polimorfismo de Nucleotídeo Único , Doença de Crohn/genética , Colite Ulcerativa/genética , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença
10.
Med Image Anal ; 97: 103225, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38908306

RESUMO

Prompt learning has demonstrated impressive efficacy in the fine-tuning of multimodal large models to a wide range of downstream tasks. Nonetheless, applying existing prompt learning methods for the diagnosis of neurological disorder still suffers from two issues: (i) existing methods typically treat all patches equally, despite the fact that only a small number of patches in neuroimaging are relevant to the disease, and (ii) they ignore the structural information inherent in the brain connection network which is crucial for understanding and diagnosing neurological disorders. To tackle these issues, we introduce a novel prompt learning model by learning graph prompts during the fine-tuning process of multimodal models for diagnosing neurological disorders. Specifically, we first leverage GPT-4 to obtain relevant disease concepts and compute semantic similarity between these concepts and all patches. Secondly, we reduce the weight of irrelevant patches according to the semantic similarity between each patch and disease-related concepts. Moreover, we construct a graph among tokens based on these concepts and employ a graph convolutional network layer to extract the structural information of the graph, which is used to prompt the pre-trained multimodal models for diagnosing neurological disorders. Extensive experiments demonstrate that our method achieves superior performance for neurological disorder diagnosis compared with state-of-the-art methods and validated by clinicians.

11.
Sci Total Environ ; 933: 172875, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38703839

RESUMO

Dry direct-seeded rice cultivation has gained popularity and expanded its cultivated area due to reduced labor requirements and water consumption. However, the impact of this cultivation method on cadmium (Cd) bioavailability in soil and the accumulation levels in grains remains uncertain. Field experiments were conducted in acidic soils at two locations in southern China to compare rice varieties and evaluate the dry direct-seeding method alongside the wet direct-seeding and traditional transplanting methods. Dry direct-seeded rice reached significantly higher Cd concentrations in its tissues starting from the heading stage than transplanted rice. Cd accumulation levels by the maturation stage in the brown rice of dry direct-seeded rice were 18.33 %-150.69 % higher than those of wet direct-seeded and transplanted rice, with a considerable ability to translocate Cd into brown rice. Furthermore, dry direct seeding decreased iron plaque formation, particularly in the amorphous Fe form; it resulted in high soil temperature and low moisture content during tillering, elevating Cd availability in the soil. Additionally, the proportion of ions and more labile forms of Cd in the soil solution was high. Moreover, the soil under dry direct seeding had high urease and acid phosphatase enzyme activities. However, low richness and diversity in the bacterial community were characterized by a significant increase in the relative abundance of Actinobacteria and Gammaproteobacteria at the class level, while exhibiting decreased relative abundances of Alphaproteobacteria, Bacilli, and KD4-96, along with fewer biomarkers. Nonetheless, these differences are gradually reduced during the maturation stage. Overall, although dry direct seeding offers several advantages, it is crucial to implement additional measures to mitigate the increased health risks linked to rice cultivation through this approach in Cd-contaminated areas.


Assuntos
Agricultura , Cádmio , Oryza , Poluentes do Solo , Solo , Oryza/metabolismo , Cádmio/metabolismo , Cádmio/análise , Poluentes do Solo/análise , Poluentes do Solo/metabolismo , China , Agricultura/métodos , Solo/química , Disponibilidade Biológica
12.
IEEE Trans Biomed Eng ; PP2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38768001

RESUMO

Freezing of gait (FOG) leads to an increased risk of falls and limited mobility in individuals with Parkinson's disease (PD). However, existing research ignores the fine-grained quantitative assessment of FOG severity. This paper provides a double-hurdle model that uses typical spatiotemporal gait features to quantify the FOG severity in patients with PD. Moreover, a novel multi-output random forest algorithm is used as one hurdle of the double-hurdle model, further enhancing the model's performance. We conduct six experiments on a public PD gait database. Results demonstrate that the designed random forest algorithm in the double-hurdle model-hyperparameter independence framework achieves outstanding performances with the highest correlation coefficient (CC) of 0.972 and the lowest root mean square error (RMSE) of 2.488. Furthermore, we study the effect of drug state on the gait patterns of PD patients with or without FOG. Results show that "OFF" state amplifies the visibility of FOG symptoms in PD patients. Therefore, this study holds significant implications for the management and treatment of PD.

13.
Environ Pollut ; 355: 124215, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38797349

RESUMO

Environmental viruses in wastewater and sludge are widely recognized for their roles in waterborne diseases. However, previous studies mainly focused on RNA viruses, and little is known about the diversity of DNA viral communities and their driving factors in municipal wastewater treatment environments. Herein, we conducted a pilot study to explore DNA virus profiles in municipal wastewater and recycled sludge by metagenomics method, and track their temporal changes in northern China. Results showed that 467 viral species were co-shared among all the samples. We identified six families of human viruses with a prevalence of 0.1%, which were rare but relatively stable in wastewater and sludge for six months. Adenoviridae, Parvoviridae, and Herpersviridae were the most dominant human viral families in municipal wastewater and recycled sludge. A time series of samples revealed that the dynamic changes of human DNA viruses were stable based on qPCR results, particularly for high-risk fecal-oral transmission viruses of adenovirus, bocavirus, polyomavirus, human gamma herpesvirus, human papillomavirus, and hepatitis B virus. Concentrations of Adenovirus (5.39-7.48 log10 copies/L) and bocavirus (4.36-7.48 log10 copies/L) were observed to be the highest in these samples compared to other viruses. Our findings demonstrated the DNA viruses' high prevalence and persistence in municipal wastewater treatment environments, highlighting the value of enhancing public health responses based on wastewater-based epidemiology.


Assuntos
Vírus de DNA , Esgotos , Águas Residuárias , China , Águas Residuárias/virologia , Vírus de DNA/genética , Esgotos/virologia , Humanos , Metagenômica , Eliminação de Resíduos Líquidos/métodos , Monitoramento Ambiental/métodos
14.
Genet Test Mol Biomarkers ; 28(6): 233-242, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38757624

RESUMO

Aims: Evaluating the association between a single nucleotide polymorphism in the 3' untranslated region (3'UTR) of the miRNA binding site of the NLRP3 gene and the occurrence and development of chronic obstructive pulmonary disease (COPD) and providing information to aid in the early detection and treatment of COPD. Materials and Methods: The regulatory single nuclear polymorphisms (SNPs) located in NLRP3 3'UTR were searched by using the dbSNP database and miRNA binding site prediction database. Meanwhile, samples from COPD patients and healthy controls in the same period were used for verification. The clinical baseline information of all subjects was collected, and the transcription level and protein expression level of NLRP3 and the expression level of inflammatory factors downstream of NLRP3 were detected. The effects of SNPs' single nucleotide changes on the transcription and expression of inflammatory factors were analyzed. Results: The study included 418 participants (249 in the COPD group and 169 in the control group). NLRP3 SNPs with miRNA binding sites include rs10754558 (G > C), rs1664774076 (ATAT > del), and rs1664775106 (C > G). Furthermore, two genotypes, GCG and GCA, were discovered to have a linkage mutation at 3'UTR 459-461. COPD susceptibility is tightly associated with the expression of the rs1664774076 del/del genotype, and the risk of COPD increased by 2.770 times (p = 0.003). Type 459-461 GCA was substantially related to the likelihood of developing COPD at various stages (p < 0.05). Except for rs10754558, all homozygous mutants increased NLRP3 mRNA and protein levels. NLRP3 had the greatest area under the receiver operating characteristic (ROC) curve for predicting the development and diagnosis of COPD when compared with its downstream inflammatory variables (AUC = 0.9291). Conclusions: The NLRP3 rs1664774076 del/del genotype is a COPD susceptibility gene, and the GCA genotype at 459-461 can be used as an early predictor of COPD exacerbation. The NLRP3 3'UTR polymorphism may alter the loss of miRNA binding sites, leading to an increase in NLRP3 expression. In the development of COPD, NLRP3 has a better diagnostic value than traditional inflammatory factors. The Clinical Trials Registration number Z: protocol KY01-2020-11-06.


Assuntos
Regiões 3' não Traduzidas , Predisposição Genética para Doença , MicroRNAs , Proteína 3 que Contém Domínio de Pirina da Família NLR , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/metabolismo , Regiões 3' não Traduzidas/genética , Polimorfismo de Nucleotídeo Único/genética , Predisposição Genética para Doença/genética , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Estudos de Casos e Controles , Sítios de Ligação/genética , Genótipo , Fatores de Risco , Alelos
15.
Artigo em Inglês | MEDLINE | ID: mdl-38568773

RESUMO

Alzheimer's Disease (AD) accounts for the majority of dementia, and Mild Cognitive Impairment (MCI) is the early stage of AD. Early and accurate diagnosis of dementia plays a vital role in more targeted treatments and effectively halting disease progression. However, the clinical diagnosis of dementia requires various examinations, which are expensive and require a high level of expertise from the doctor. In this paper, we proposed a classification method based on multi-modal data including Electroencephalogram (EEG), eye tracking and behavioral data for early diagnosis of AD and MCI. Paradigms with various task difficulties were used to identify different severity of dementia: eye movement task and resting-state EEG tasks were used to detect AD, while eye movement task and delayed match-to-sample task were used to detect MCI. Besides, the effects of different features were compared and suitable EEG channels were selected for the detection. Furthermore, we proposed a data augmentation method to enlarge the dataset, designed an extra ERPNet feature extract layer to extract multi-modal features and used domain-adversarial neural network to improve the performance of MCI diagnosis. We achieved an average accuracy of 88.81% for MCI diagnosis and 100% for AD diagnosis. The results of this paper suggest that our classification method can provide a feasible and affordable way to diagnose dementia.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Redes Neurais de Computação , Diagnóstico Precoce
16.
Sci Total Environ ; 927: 172251, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38604355

RESUMO

Animal hosts harbor diverse assemblages of microbial symbionts that play crucial roles in the host's lifestyle. The link between microbial symbiosis and host development remains poorly understood. In particular, little is known about the adaptive evolution of gut bacteria in host-microbe symbioses. Recently, symbiotic relationships have been categorized as open, closed, or mixed, reflecting their modes of inter-host transmission and resulting in distinct genomic features. Members of the genus Bacteroides are the most abundant human gut microbiota and possess both probiotic and pathogenic potential, providing an excellent model for studying pan-genome evolution in symbiotic systems. Here, we determined the complete genome of an novel clinical strain PL2022, which was isolated from a blood sample and performed pan-genome analyses on a representative set of Bacteroides cellulosilyticus strains to quantify the influence of the symbiotic relationship on the evolutionary dynamics. B. cellulosilyticus exhibited correlated genomic features with both open and closed symbioses, suggesting a mixed symbiosis. An open pan-genome is characterized by abundant accessory gene families, potential horizontal gene transfer (HGT), and diverse mobile genetic elements (MGEs), indicating an innovative gene pool, mainly associated with genomic islands and plasmids. However, massive parallel gene loss, weak purifying selection, and accumulation of positively selected mutations were the main drivers of genome reduction in B. cellulosilyticus. Metagenomic read recruitment analyses showed that B. cellulosilyticus members are globally distributed and active in human gut habitats, in line with predominant vertical transmission in the human gut. However, existence and/or high abundance were also detected in non-intestinal tissues, other animal hosts, and non-host environments, indicating occasional horizontal transmission to new niches, thereby creating arenas for the acquisition of novel genes. This case study of adaptive evolution under a mixed host-microbe symbiosis advances our understanding of symbiotic pan-genome evolution. Our results highlight the complexity of genetic evolution in this unusual intestinal symbiont.


Assuntos
Bacteroides , Microbioma Gastrointestinal , Genoma Bacteriano , Simbiose , Microbioma Gastrointestinal/genética , Bacteroides/genética , Bacteroides/fisiologia , Humanos , Evolução Molecular , Transferência Genética Horizontal
17.
Environ Pollut ; 349: 123908, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38570157

RESUMO

Paddy Crusts (PC) play a pivotal role in the migration and transformation of heavy metals within paddy ecosystems, situated at the critical intersection of air, water, and soil. This study focused on PC samples from heavy metal-contaminated rice paddies in six southern Chinese provinces. It's the first time we've screened and quantified the impact of nutrition, physicochemical properties, and heavy metals on bacterial diversity in PC. Our results highlight the significant influence of zinc, total nitrogen, and soil manganese on bacterial diversity. Using structural equation models, we identified the pathways through which these three types of environmental factors shape bacterial diversity. Heavy metal indicators and physical and chemical indicators exerted a direct negative effect on bacterial diversity in PC, while nutritional indicators had a direct and significant positive effect on bacterial diversity. Variance partitioning analysis revealed heavy metals had the most significant impact, accounting for 7.77% of the total effect. Moreover, the influence of heavy metals on bacterial diversity increased as diversity decreased, ranging from 3.81% to 42.09%. To remediate specific heavy metal pollution, our proposed method involves cultivating indigenous bacteria by controlling these environmental factors, based on an analysis of the interplay among bacterial diversity, environmental variables, and heavy metal bioconcentration factors. These findings enhance our understanding of PC and provide insights into rice field heavy metal pollution mitigation.


Assuntos
Metais Pesados , Oryza , Microbiologia do Solo , Poluentes do Solo , Metais Pesados/análise , China , Poluentes do Solo/análise , Bactérias/efeitos dos fármacos , Monitoramento Ambiental/métodos , Ecossistema , Solo/química , Agricultura
18.
Arch Microbiol ; 206(5): 232, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38658486

RESUMO

Ibuprofen (IBU) and naproxen (NPX), as widely prescribed non-steroidal anti-inflammatory drugs (NSAIDs), are largely produced and consumed globally, leading to frequent and ubiquitous detection in various aqueous environments. Previously, the microbial transformation of them has been given a little attention, especially with the isolated fungus. A yeast-like Apiotrichum sp. IB-1 has been isolated and identified, which could simultaneously transform IBU (5 mg/L) and NPX (2.5 mg/L) with maximum efficiencies of 95.77% and 88.31%, respectively. For mono-substrate, the transformation efficiency of IB-1 was comparable to that of co-removal conditions, higher than most of isolates so far. IBU was oxidized mainly through hydroxylation (m/z of 221, 253) and NPX was detoxified mainly via demethylation (m/z of 215) as shown by UPLC-MS/MS results. Based on transcriptome analysis, the addition of IBU stimulated the basic metabolism like TCA cycle. The transporters and respiration related genes were also up-regulated accompanied with higher expression of several dehydrogenase, carboxylesterase, dioxygenase and oxidoreductase encoding genes, which may be involved in the transformation of IBU. The main functional genes responsible for IBU and NPX transformation for IB-1 should be similar in view of previous studies, which needs further confirmation. This fungus would be useful for potential bioremediation of NSAIDs pollution and accelerate the discovery of functional oxidative genes and enzymes different from those of bacteria.


Assuntos
Anti-Inflamatórios não Esteroides , Biotransformação , Ibuprofeno , Naproxeno , Ibuprofeno/metabolismo , Naproxeno/metabolismo , Anti-Inflamatórios não Esteroides/metabolismo , Biodegradação Ambiental
19.
Angew Chem Int Ed Engl ; 63(23): e202403245, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38578838

RESUMO

The encapsulation of functional colloidal nanoparticles (100 nm) into single-crystalline ZSM-5 zeolites, aiming to create uniform core-shell structures, is a highly sought-after yet formidable objective due to significant lattice mismatch and distinct crystallization properties. In this study, we demonstrate the fabrication of a core-shell structured single-crystal zeolite encompassing an Fe3O4 colloidal core via a novel confinement stepwise crystallization methodology. By engineering a confined nanocavity, anchoring nucleation sites, and executing stepwise crystallization, we have successfully encapsulated colloidal nanoparticles (CN) within single-crystal zeolites. These grafted sites, alongside the controlled crystallization process, compel the zeolite seed to nucleate and expand along the Fe3O4 colloidal nanoparticle surface, within a meticulously defined volume (1.5×107≤V≤1.3×108 nm3). Our strategy exhibits versatility and adaptability to an array of zeolites, including but not restricted to ZSM-5, NaA, ZSM-11, and TS-1 with polycrystalline zeolite shell. We highlight the uniformly structured magnetic-nucleus single-crystalline zeolite, which displays pronounced superparamagnetism (14 emu/g) and robust acidity (~0.83 mmol/g). This innovative material has been effectively utilized in a magnetically stabilized bed (MSB) reactor for the dehydration of ethanol, delivering an exceptional conversion rate (98 %), supreme ethylene selectivity (98 %), and superior catalytic endurance (in excess of 100 hours).

20.
Nanoscale ; 16(19): 9317-9324, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38656387

RESUMO

For atomically thin two-dimensional materials, variations in layer thickness can result in significant changes in the electronic energy band structure and physicochemical properties, thereby influencing the carrier dynamics and device performance. In this work, we employ time- and energy-resolved photoemission electron microscopy to reveal the ultrafast carrier dynamics of PdSe2 with different layer thicknesses. We find that for few-layer PdSe2 with a semiconductor phase, an ultrafast hot carrier cooling on a timescale of approximately 0.3 ps and an ultrafast defect trapping on a timescale of approximately 1.3 ps are unveiled, followed by a slower decay of approximately tens of picoseconds. However, for bulk PdSe2 with a semimetal phase, only an ultrafast hot carrier cooling and a slower decay of approximately tens of picoseconds are observed, while the contribution of defect trapping is suppressed with the increase of layer number. Theoretical calculations of the electronic energy band structure further confirm the transition from a semiconductor to a semimetal. Our work demonstrates that TR- and ER-PEEM with ultrahigh spatiotemporal resolution and wide-field imaging capability has great advantages in revealing the intricate details of ultrafast carrier dynamics of nanomaterials.

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