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1.
Front Psychiatry ; 15: 1426336, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39483732

RESUMEN

Background: Depression is a significant risk factor affecting the mental health of older adults. In the context of accelerated population aging and the policy of "delayed retirement," self-employment has become an important alternative for older adults. Thus, studying the difference in depression levels between self-employed older adults and retirees, along with the mechanisms behind these differences, has emerged as a crucial theoretical and practical issue. Methods: This research, based on panel data from the China Health and Retirement Longitudinal Study for the years 2011, 2013, 2015, and 2018, employed fixed-effect, instrumental variable, mediation models to analyze the difference in depression levels between self-employed older adults and retirees, as well as the mediating mechanisms involved. Results: The findings indicate that self-employed older adults have lower levels of depression than retirees. The results of the mediating mechanism analysis suggest that self-employment can indirectly lower the depression levels of older adults by frequent social participation and greater life satisfaction. However, heterogeneity analysis revealed significant urban-rural differences and different types of self-employment in the impact of self-employment on the depression levels of older adults. Conclusions: The results of this study are of great significance for enhancing the mental health of older adults and provide empirical support for China and other developing countries in formulating more effective aging policies and building a more beneficial aging society.

2.
Sci Adv ; 10(42): eado4935, 2024 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-39423264

RESUMEN

Shape-controlled alloy nanoparticle catalysts have been shown to exhibit improved performance in the oxygen reduction reaction (ORR) in liquid half-cells. However, translating the success to catalyst layers in fuel cells faces challenges due to the more demanding operation conditions in membrane electrode assembly (MEA). Balancing durability and activity is crucial. Here, we developed a strategy that limits the atomic diffusion within surface layers, fostering the phase transition and shape retention during thermal treatment. This enables selective transformation of platinum-iron nanowire surfaces into intermetallic structures via atomic ordering at a low temperature. The catalysts exhibit enhanced MEA stability with 50% less Fe loss while maintaining high catalytic activity comparable to that in half-cells. Density functional calculations suggest that the ordered intermetallic surface stabilizes morphology against rapid corrosion and improves the ORR activity. The surface engineering through atomic ordering presents potential for practical application in fuel cells with shape-controlled Pt-based alloy catalysts.

3.
Mol Immunol ; 175: 1-9, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39265360

RESUMEN

The NSP14 protein of SARS-CoV-2 not only facilitates viral replication but also plays a pivotal role in activating the host immune system by enhancing cytokine production. In this study, we found that NSP14 markedly activated the activator protein 1 (AP-1) pathway by increasing the phosphorylation of ERK (p-ERK), which enters the nucleus and promotes AP-1 transcription. The screening of the main proteins of the ERK pathway revealed that NSP14 could interact with MEK, a kinase of ERK, and increase the level of phosphorylated MEK. The addition of the MEK inhibitor U0126 suppressed the level of p-ERK induced by NSP14 and partly blocked cytokine production, suggesting that NSP14 activates MEK to enhance AP-1 signaling. Further investigation demonstrated that the ExoN domain of NSP14 might be crucial for the interaction and activation of MEK. These results suggest a novel mechanism by which NSP14 of SARS-CoV-2 induces a proinflammatory response in the host.

4.
Environ Res ; 262(Pt 1): 119855, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39208972

RESUMEN

Urease found in a wide range of microorganisms plays a vital role in ureolytic induced calcite precipitation (UICP). However, the genomic information on urease-producing strains is limited, and there is a need for further in-depth studies on aspects such as the regulation of urease activity by nickel ligand residues. The present study delved into the elucidation of urease activity in a newly isolated strain YX-3 coupled with nickel-ligand residues by employing the genetic architecture of biomineralization-controlled growth, molecular docking, molecular dynamics simulation (MDS), and site-directed mutagenesis. Genome-wide sequencing showed the presence of urease gene clusters, comprising structural genes ureA, ureB, and ureC, alongside auxiliary genes ureD, ureE, ureF, and ureG. RT-qPCR analysis showed that the addition of NiCl2 resulted in a significant up-regulation of ureC expression. His267, His294, and Gly325 in the domain of UreC were further proved to coordinate with nickel ions and urea simultaneously through homology modeling and molecular docking, and molecular dynamics simulations (MDS) showed the urease-urea docking complexes exhibited degressive binding stability by four metrics including root mean square deviations (RMSD) when those residues were mutated into alanine respectively. Western blotting exhibited that mutations of H267A, H294A, and G325A led to a reduction in the relative expression of urease, wherein urease activity was about 62%, 45%, and 20% times that of the wild type (WT), respectively. The overexpression results further confirmed the importance of these residues for urease activity and CaCO3 precipitation. These results would help to deepen the understanding of urease-producing strains at a molecular level and expand the theoretical basis for modulating urease activity.

5.
Artículo en Inglés | MEDLINE | ID: mdl-39113542

RESUMEN

Recent studies have reported increasing complexity in human immunodeficiency virus 1 (HIV-1) genotypes among men who have sex with men (MSM) in China. In an HIV-1 molecular epidemiological study conducted among MSM in Yunnan Province, China, we discovered that four samples could potentially represent a circulating recombinant form (CRF). In this study, we conducted further analysis on their nearly full-length genome (NFLG) sequences. The NFLG sequences formed a distinct monophyletic clade in the phylogenetic tree. Recombination analysis indicated that the four sequences were constructed upon the backbone of CRF149_01B, with the insertion of three CRF07_BC fragments. Consequently, they were designated as CRF150_cpx. Evolutionary analyses suggested that CRF150_cpx emerged between approximately 2014 and 2015. The identification of new CRFs not only deepens our understanding of HIV recombination but also aids in comprehending the prevalence and transmission history of HIV among specific populations.

6.
Am J Med Sci ; 368(5): 476-484, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38992750

RESUMEN

AIM: The present study was conducted to measure the expression of early growth response factor 3 (Egr3), inflammatory cytokines (IL-1ß, IL-6), vascular endothelial growth factor (VEGF) and NF-κB in patients with coronary artery disease (CAD) to investigate the relationships of these molecules and Egr3 gene expression. METHODS: We recruited 132 CAD patients and 63 healthy individuals. The expression levels of Egr3, VEGF, p50 and p65 were measured by reverse transcription quantitative polymerase chain reaction and the levels of Egr3, IL-1ß and IL-6 in patients serum and in human coronary artery endothelial cells (HCAECs) were measured by enzyme-linked immunosorbent assay (ELISAs) in CAD patients. HCAECs were treated with ox-LDL to establish an in vitro atherosclerosis model. An oil red O staining assay was used to assess the lipid droplet formation. A colloidal external lumen formed by Matrigel was used to test the migration of HCAECs. The expression of Egr3, VEGF and NF-κB was determined by Western blotting. RESULTS: The levels of serum Egr3 and IL-6 in the severe stenosis group were greater than those in the mild stenosis group and controls (p < 0.05). The level of serum IL-1ß in the severe stenosis group was greater than that in the control group (p < 0.05). Moreover, Egr3 expression was positively associated with IL-6 levels (r = 0.55, p < 0.001), IL-1ß levels (r = 0.21, p = 0.004) and the Gensini score (r = 0.20, p = 0.02). We also found that Egr3 expression was significantly greater in CAD patients than that in controls. And its expression was highest in the mild patients. The expression of VEGF, P50 and P65 was also greater in CAD patients. In the in vitro experiment, we found that the inhibition of Egr3 expression significantly reduced the expression levels of p50, p65, IL-6 and CRP. Moreover, the inhibition of Egr3 expression significantly reduced the lipid droplet formation and decreased capability of lumen formation. CONCLUSIONS: In the pathogenesis of atherosclerosis, Egr3 gene expression may induce the expression of inflammatory factors and lipid droplet formation and lumen formation, which could promote the atherosclerosis development.


Asunto(s)
Enfermedad de la Arteria Coronaria , Proteína 3 de la Respuesta de Crecimiento Precoz , FN-kappa B , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular , Humanos , Masculino , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/sangre , Femenino , Enfermedad de la Arteria Coronaria/metabolismo , Persona de Mediana Edad , Proteína 3 de la Respuesta de Crecimiento Precoz/metabolismo , Proteína 3 de la Respuesta de Crecimiento Precoz/genética , FN-kappa B/metabolismo , Células Endoteliales/metabolismo , Anciano , Interleucina-6/metabolismo , Interleucina-6/sangre , Vasos Coronarios/metabolismo , Células Cultivadas , Interleucina-1beta/metabolismo , Estudios de Casos y Controles
7.
Braz J Med Biol Res ; 57: e13409, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38958367

RESUMEN

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains the leading cause of mortality by a single infectious agent in the world. M. tuberculosis infection could also result in clinical chronic infection, known as latent TB infection (LTBI). Compared to the current limited treatment, several subunit vaccines showed immunotherapeutic effects and were included in clinical trials. In this study, a subunit vaccine of Ag85B with a novel mucosal adjuvant c-di-AMP (Ag85B:c-di-AMP) was delivered intranasally to a persistent M. tuberculosis H37Ra infection mouse model, which also presented the asymptomatic characteristics of LTBI. Compared with Ag85B immunization, Ag85B:c-di-AMP vaccination induced stronger humoral immune responses, significantly higher CD4+ T cells recruitment, enhanced Th1/Th2/Th17 profile response in the lung, decreased pathological lesions of the lung, and reduced M. tuberculosis load in mice. Taken together, Ag85B:c-di-AMP mucosal route immunization provided an immunotherapeutic effect on persistent M. tuberculosis H37Ra infection, and c-di-AMP, as a promising potential mucosal adjuvant, could be further used in therapeutic or prophylactic vaccine strategies for persistent M. tuberculosis infection as well as LTBI.


Asunto(s)
Adyuvantes Inmunológicos , Modelos Animales de Enfermedad , Mycobacterium tuberculosis , Vacunas contra la Tuberculosis , Animales , Adyuvantes Inmunológicos/administración & dosificación , Vacunas contra la Tuberculosis/inmunología , Vacunas contra la Tuberculosis/administración & dosificación , Mycobacterium tuberculosis/inmunología , Ratones , Femenino , Antígenos Bacterianos/inmunología , Aciltransferasas/inmunología , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/administración & dosificación , Proteínas Bacterianas/inmunología , Tuberculosis/inmunología , Tuberculosis/prevención & control , Tuberculosis Latente/inmunología , Ratones Endogámicos BALB C , Administración Intranasal
8.
China CDC Wkly ; 6(27): 658-664, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-39027632

RESUMEN

What is already known about this topic?: HIV transmission among serodiscordant couples remains a persistent issue in China. However, the practice of combining counseling with antiretroviral therapies (ART) to enhance ART adherence is not widely implemented or recommended in Chinese health guidelines. What is added by this report?: This randomized controlled trial suggests that increased follow-up, counseling, and awareness of HIV risk can enhance ART compliance, thereby maximizing treatment efficacy. What are the implications for public health practice?: Early testing and counseling of serodiscordant couples, following the identification of a human immunodeficiency virus (HIV) positive spouse, is crucial for initiating ART and reducing the risk of seroconversion in the uninfected partner. Implementing a combination of ART and adjunct counseling in China is advisable.

9.
Artículo en Inglés | MEDLINE | ID: mdl-38959124

RESUMEN

The border areas of Yunnan Province in China are severely affected by human immunodeficiency virus (HIV). To investigate the risk of HIV transmission and assess the prevalence of pretreatment drug resistance (PDR) in the border area, blood samples were collected from individuals with newly reported HIV in 2021 in three border counties (Cangyuan, Gengma, and Zhenkang) in Yunnan Province. Among the 174 samples successfully genotyped, eight circulating recombinant forms (CRFs), two subtypes, and several unique recombinant forms (URFs) were identified. CRF08_BC (56.9%, 99/174), URFs (14.4%, 25/174), CRF01_AE (10.9%, 19/174), and CRF07_BC (8.0%, 14/174) were the main genotypes. CRF08_BC and URFs were detected more frequently in Chinese and Burmese individuals, respectively. CRF07_BC was found more frequently in men who have sex with men. The proportion of individuals detected in HIV-1 networks was only associated with case-reporting counties. When stratified by county, individuals aged ≤40 years in Cangyuan and ≥41 years in Gengma were more likely to be found in these networks. Furthermore, 93.8% (15/16) of the links in Cangyuan and 79.4% (50/63) of those in Gengma were located within their own counties. The prevalence of PDR to any antiretroviral drug, nucleoside reverse transcriptase inhibitors (NRTIs), and non-nucleoside reverse transcriptase inhibitors (NNRTIs) were 10% (17/170), 0.6% (1/170), and 9.4% (16/170), respectively. The most frequent resistance-associated mutations (RAMs) were V179D/VD/E/T (22.9%, 39/170) and E138A/G/K/R (13.5%, 23/170). In the molecular networks, six clusters shared common RAMs. HIV-1 genetics has become more diverse in border areas. HIV-1 molecular network analysis revealed the different characteristics of the HIV-1 epidemic in the border counties. The prevalence of PDR showed an upward trend, and the PDR to NNRTIs was close to the public response threshold. These findings provide information for the development of AIDS prevention and treatment strategies.

11.
Nano Lett ; 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38843402

RESUMEN

High-entropy alloys (HEAs) have garnered considerable attention as promising nanocatalysts for effectively utilizing Pt in catalysis toward oxygen reduction reactions due to their unique properties. Nonetheless, there is a relative dearth of attention regarding the structural evolution of HEAs in response to electrochemical conditions. In this work, we propose a thermal reduction method to synthesize high entropy nanoparticles by leveraging the confinement effect and abundant nitrogen-anchored sites provided by pyrolyzed metal-organic frameworks (MOFs). Notably, the prepared catalysts exhibit enhanced activity accompanied by structural reconstruction during electrochemical activation, approaching 1 order of magnitude higher mass activity compared to Pt/C in oxygen reduction. Atomic-scale structural characterization reveals that abundant defects and single atoms are formed during the activation process, contributing to a significant boost in the catalytic performance for oxygen reduction reactions. This study provides deep insights into surface reconstruction engineering during electrochemical operations, with practical implications for fuel cell applications.

12.
Sci Rep ; 14(1): 11506, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38769108

RESUMEN

The optimal design of groundwater circulation wells (GCWs) is challenging. The key to purifying groundwater using this technique is its proficiency and productivity. However, traditional numerical simulation methods are limited by long modeling times, random optimization schemes, and optimization results that are not comprehensive. To address these issues, this study introduced an innovative approach for the optimal design of a GCW using machine learning methods. The FloPy package was used to create and implement the MODFLOW and MODPATH models. Subsequently, the formulated models were employed to calculate the characteristic indicators of the effectiveness of the GCW operation, including the radius of influence (R) and the ratio of particle recovery (Pr). A detailed collection of 3000 datasets, including measures of operational efficiency and key elements in machine learning, was meticulously compiled into documents through model execution. The optimization models were trained and evaluated using multiple linear regression (MLR), artificial neural networks (ANN), and support vector machines (SVM). The models produced by the three approaches exhibited notable correlations between anticipated outcomes and datasets. For the optimal design of circulating well parameters, machine learning methods not only improve the optimization speed, but also expand the scope of parameter optimization. Consequently, these models were applied to optimize the configuration of the GCW at a site in Xi'an. The optimal scheme for R (Q = 293.17 m3/d, a = 6.09 m, L = 7.28 m) and optimal scheme for Pr (Q = 300 m3/d, a = 3.64 m, L = 1 m) were obtained. The combination of numerical simulations and machine learning is an effective tool for optimizing and predicting the GCW remediation effect.

13.
Altern Ther Health Med ; 30(5): 136-140, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38743887

RESUMEN

Objective: To investigate the molecular mechanism of sevoflurane affecting the development of the offspring's nervous system through the GABAAR/Sirt 1 pathway. Methods: Pregnant rats were obtained by mating females and males, and were randomly divided into 3 h sevoflurane (2.3% sevoflurane anesthesia for 3 h), 6 h sevoflurane (2.3% sevoflurane anesthesia for 6 h), Sirt-1 activator-SRT1720 (10 mg/kg SRT1720), 6 h sevoflurane+SRT1720 (10 mg/kg SRT1720) and control groups) group and control group, 31-day-old littermates were taken out and their learning and memory functions were examined by the water maze experiment; the heads were severed to remove the brains, and the kits were used to detect the levels of 5-HT and Ach in the brain tissue; the hippocampal tissues of the littermates were isolated, and neuronal damage in the hippocampal tissues was assessed by Nissen staining; neuronal apoptosis in the hippocampal tissues was detected by TUNEL staining; and GABAAR in the hippocampal tissues was detected by Western blot. GABAAR, Sirt-1, and apoptosis-related proteins (Caspase-3, BCL-2, BAX) in hippocampal tissue. Results: Compared with the control group, the 3 h sevoflurane group and the 6 h sevoflurane group neurons were arranged sparsely, the cells appeared to be swollen, the evasion latency, the apoptosis rate of neurons, the expression of Caspase-3, and BAX increased significantly, and the number of crossing the plateau, the level of 5-HT and Ach in the brain tissues, and the expression of GABAAR, Sirt-1, and BCL-2 were decreased significantly, and the differences existed between the groups (P < .5); compared with the 6 h sevoflurane group, neuronal morphological changes in the hippocampal tissue of the 6 h sevoflurane+SRT1720 group were improved, with a significant decrease in the evasion latency, neuronal apoptosis rate, expression of Caspase-3 and BAX, and a significant increase in the number of traversing platforms, brain tissue 5-HT, Ach level, GABAAR, Sirt-1, and BCL-2 expression (P < .5); compared with the SRT1720 group, the neurons in the 6 h sevoflurane + SRT1720 group were sparsely arranged, with a significant increase in evasion latency, neuronal apoptosis rate, caspase-3, BAX expression, and a significant decrease in the number of traversing platforms, brain tissue 5-HT, Ach level, GABAAR, Sirt-1, and BCL-2 expression (P < .5 ). Conclusion: Sevoflurane can affect the neurological development of rat offspring, which may be related to the inhibition of Sirt-1 expression.


Asunto(s)
Sevoflurano , Sirtuina 1 , Sevoflurano/farmacología , Animales , Sirtuina 1/metabolismo , Ratas , Femenino , Embarazo , Anestésicos por Inhalación/farmacología , Receptores de GABA-A/metabolismo , Receptores de GABA-A/efectos de los fármacos , Masculino , Ratas Sprague-Dawley , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Apoptosis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos
14.
Front Plant Sci ; 15: 1384246, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38601316

RESUMEN

Introduction: Salt tolerance during seed germination is an important trait for direct seeding and low-cost rice production. Nevertheless, it is still not clear how seed germination under salt stress is regulated genetically. Methods: In this study, genome-wide association studies (GWAS) were performed to decipher the genetic basis of seed germination under salt stress using 541 rice varieties collected worldwide. Results and discussion: Three quantitative trait loci (QTLs) were identified including qGRG3-1 on chromosome 3, qGRG3-2 on chromosome 5, and qGRG4 on chromosome 4. Assessment of candidate genes in these loci for their responses to salt stress identified a TATA modulatory factor (OsTMF) in qGRG3-2. The expression of OsTMF was up-regulated in both roots and shoots after exposure to salt stress, and OsTMF knockout mutants exhibited delayed seed germination under salt stress. Haplotype analysis showed that rice varieties carrying OsTMF-Hap2 displayed elevated salt tolerance during seed germination. These results provide important knowledge and resources to improve rice seed germination under salt stress in the future.

15.
J Lipid Res ; 65(3): 100514, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38309418

RESUMEN

Human genetic evidence suggests a protective role of loss-of-function variants in 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13) for liver fibrotic diseases. Although there is limited preclinical experimental data on Hsd17b13 antisense oligonucleotide (ASO) or siRNA in a fibrosis model, several ASO and siRNA approaches are being tested clinically as potential therapies for nonalcoholic steatohepatitis (NASH). The aim of this study was to assess the therapeutic potential of Hsd17b13 ASO in a preclinical advanced NASH-like hepatic fibrosis in vivo model. In vitro testing on primary hepatocytes demonstrated that Hsd17b13 ASO exhibited strong efficacy and specificity for knockdown of the Hsd17b13 gene. In choline-deficient, L-amino acid-defined, HFD (CDAHFD)-induced steatotic and fibrotic mice, therapeutic administration of Hsd17b13 ASO resulted in a significant and dose-dependent reduction of hepatic Hsd17b13 gene expression. The CDAHFD group exhibited considerably elevated liver enzyme levels, hepatic steatosis score, hepatic fibrosis, and increased fibrotic and inflammatory gene expression, indicating an advanced NASH-like hepatic fibrosis phenotype. Although Hsd17b13 ASO therapy significantly affected hepatic steatosis, it had no effect on hepatic fibrosis. Our findings demonstrate, for the first time, that Hsd17b13 ASO effectively suppressed Hsd17b13 gene expression both in vitro and in vivo, and had a modulatory effect on hepatic steatosis in mice, but did not affect fibrosis in the CDAHFD mouse model of NASH.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Animales , Ratones , Modelos Animales de Enfermedad , Hígado/metabolismo , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/genética , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/genética , Oligonucleótidos Antisentido/genética , Oligonucleótidos Antisentido/farmacología , Oligonucleótidos Antisentido/uso terapéutico , ARN Interferente Pequeño/metabolismo
17.
Braz. j. med. biol. res ; 57: e13409, fev.2024. graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1564163

RESUMEN

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains the leading cause of mortality by a single infectious agent in the world. M. tuberculosis infection could also result in clinical chronic infection, known as latent TB infection (LTBI). Compared to the current limited treatment, several subunit vaccines showed immunotherapeutic effects and were included in clinical trials. In this study, a subunit vaccine of Ag85B with a novel mucosal adjuvant c-di-AMP (Ag85B:c-di-AMP) was delivered intranasally to a persistent M. tuberculosis H37Ra infection mouse model, which also presented the asymptomatic characteristics of LTBI. Compared with Ag85B immunization, Ag85B:c-di-AMP vaccination induced stronger humoral immune responses, significantly higher CD4+ T cells recruitment, enhanced Th1/Th2/Th17 profile response in the lung, decreased pathological lesions of the lung, and reduced M. tuberculosis load in mice. Taken together, Ag85B:c-di-AMP mucosal route immunization provided an immunotherapeutic effect on persistent M. tuberculosis H37Ra infection, and c-di-AMP, as a promising potential mucosal adjuvant, could be further used in therapeutic or prophylactic vaccine strategies for persistent M. tuberculosis infection as well as LTBI.

18.
Signal Transduct Target Ther ; 9(1): 15, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38195689

RESUMEN

Human microorganisms, including bacteria, fungi, and viruses, play key roles in several physiological and pathological processes. Some studies discovered that tumour tissues once considered sterile actually host a variety of microorganisms, which have been confirmed to be closely related to oncogenesis. The concept of intratumoural microbiota was subsequently proposed. Microbiota could colonise tumour tissues through mucosal destruction, adjacent tissue migration, and hematogenic invasion and affect the biological behaviour of tumours as an important part of the tumour microenvironment. Mechanistic studies have demonstrated that intratumoural microbiota potentially promote the initiation and progression of tumours by inducing genomic instability and mutations, affecting epigenetic modifications, promoting inflammation response, avoiding immune destruction, regulating metabolism, and activating invasion and metastasis. Since more comprehensive and profound insights about intratumoral microbiota are continuously emerging, new methods for the early diagnosis and prognostic assessment of cancer patients have been under examination. In addition, interventions based on intratumoural microbiota show great potential to open a new chapter in antitumour therapy, especially immunotherapy, although there are some inevitable challenges. Here, we aim to provide an extensive review of the concept, development history, potential sources, heterogeneity, and carcinogenic mechanisms of intratumoural microorganisms, explore the potential role of microorganisms in tumour prognosis, and discuss current antitumour treatment regimens that target intratumoural microorganisms and the research prospects and limitations in this field.


Asunto(s)
Microbiota , Neoplasias , Humanos , Neoplasias/genética , Neoplasias/terapia , Inmunoterapia , Carcinogénesis/genética , Transformación Celular Neoplásica , Microbiota/genética , Microambiente Tumoral/genética
19.
Front Immunol ; 14: 1183426, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37908343

RESUMEN

Dual-graft liver transplantation (DGLT) expands the pool of donors, ensures the safety of the donors, and treats a potential small for size syndrome (SFSS). However, some of the recipient graft showed atrophy. The cause and mechanism of the unbalanced proliferation and atrophy of dual grafts after clinical DGLT have not been clarified. We established and optimized the rat model of DGLT to explore the causes of growth unbalance. Continuously and dynamically observed bilateral graft volume and portal vein blood flow change by magnetic resonance imaging (MRI) and ultrasound (US). We detected liver function indexes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL). Liver samples from receptors were obtained for morphology, and apoptosis was measured by RT-PCR and western blot. Optimization of the model improved the 7-day survival rate from former 58.3% to 87.5%, and the 30-day survival rate was 68.8%. The volume of the right graft gradually increased, and the left graft atrophied during the 30-day observation period. The portal blood flow of the left graft gradually decreased until the 30th day (0.13 ± 0.01 ml/s) compared with the sham group (0.63 ± 0.05 ml/s), and the right graft significantly increased on the 30th day (0.75 ± 0.11ml/s). The liver function initially increased and then recovered. The total volume (12.52 ± 1.60 ml vs 4.47 ± 0.08 ml) and weight (12.09 ± 1 g vs 4.91 ± 0.18 g) of the graft increased significantly compared to pre-transplantation and reached the level of the sham operation group on the 30th day. The volume and weight of the right graft increased more than those of the left graft (P < 0.05). There was more inflammatory cell infiltration in the left graft, and the right graft had obvious proliferation of hepatocytes and mature bile duct cells. Left grafts were more prone to apoptosis than right grafts (P < 0.05). In conclusion, growth of the right graft is superior to the left; after double liver transplantation, perfusion blood flow and apoptosis may be the reason contributing to the volume differences in dual grafts.


Asunto(s)
Trasplante de Hígado , Ratas , Animales , Humanos , Trasplante de Hígado/métodos , Donadores Vivos , Hígado , Bilirrubina , Atrofia
20.
Front Microbiol ; 14: 1277709, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38029179

RESUMEN

In this study, a highly promising bacterium was isolated from sandstone oil in the Ordos Basin, named strain NS-6 which exhibited exceptional urease production ability and demonstrated superior efficiency in inducing the deposition of calcium carbonate (CaCO3). Through morphological and physiochemical characteristics analysis, as well as 16S rRNA sequencing, strain NS-6 was identified as Neobacillus mesonae. The activity of urease and the formation of CaCO3 increased over time, reaching a maximum of 7.9 mmol/L/min and 184 mg (4.60 mg/mL) respectively at 32 h of incubation. Scanning Electron Microscopy (SEM) revealed CaCO3 crystals ranging in size from 5 to 6 µm, and Energy Dispersive X-ray (EDX) analysis verified the presence of calcium, carbon, and oxygen within the crystals. X-ray Diffraction (XRD) analysis further confirmed the composition of these CaCO3 crystals as calcite and vaterite. Furthermore, the maximum deposition of CaCO3 by strain NS-6 was achieved using response surface methodology (RSM), amounting to 193.8 mg (4.845 mg/mL) when the concentration of calcium ions was 0.5 mmol/L supplemented with 0.9 mmol/L of urea at pH 8.0. Genome-wide analysis revealed that strain NS-6 possesses a chromosome of 5,736,360 base pairs, containing 5,442 predicted genes, including 3,966 predicted functional genes and 1,476 functionally unknown genes. Genes like ureA, ureB, and ureC related to urea catabolism were identified by gene annotation, indicating that strain NS-6 is a typical urease-producing bacterium and possesses a serial of genes involved in metabolic pathways that mediated the deposition of CaCO3 at genetic level.

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