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Complex organisms generate differential gene expression through the same set of DNA sequences in distinct cells. The communication between chromatin and RNA regulates cellular behavior in tissues. However, little is known about how chromatin, especially histone modifications, regulates RNA polyadenylation. In this study, we found that FUS was recruited to chromatin by H3K36me3 at gene bodies. The H3K36me3 recognition of FUS was mediated by the proline residues in the ZNF domain. After these proline residues were mutated or H3K36me3 was abolished, FUS dissociated from chromatin and bound more to RNA, resulting in an increase in polyadenylation sites far from stop codons genome-wide. A proline mutation corresponding to a mutation in amyotrophic lateral sclerosis contributed to the hyperactivation of mitochondria and hyperdifferentiation in mouse embryonic stem cells. These findings reveal that FUS is an H3K36me3 reader protein that links chromatin-mediated alternative polyadenylation to human disease.
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Histonas , Poliadenilação , Proteína FUS de Ligação a RNA , Animais , Humanos , Camundongos , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Diferenciação Celular/genética , Cromatina/metabolismo , Cromatina/genética , Células HEK293 , Histonas/metabolismo , Histonas/genética , Mitocôndrias/metabolismo , Mitocôndrias/genética , Células-Tronco Embrionárias Murinas , Mutação , Poliadenilação/genética , Proteína FUS de Ligação a RNA/genética , Proteína FUS de Ligação a RNA/metabolismo , Linhagem Celular , Domínios ProteicosRESUMO
BACKGROUND AND AIMS: Epigenetic reprogramming and escape from terminal differentiation are poorly understood enabling characteristics of liver cancer. Keratin 19 (KRT19), classically known to form the intermediate filament cytoskeleton, is a marker of stemness and worse prognosis in liver cancer. This study aimed to address the functional roles of KRT19 in liver tumorigenesis and to elucidate the underlying mechanisms. APPROACH AND RESULTS: Using multiplexed genome editing of hepatocytes in vivo, we demonstrated that KRT19 promoted liver tumorigenesis in mice. Cell fractionation revealed a previously unrecognized nuclear fraction of KRT19. Tandem affinity purification identified histone deacetylase 1 and REST corepressor 1, components of the corepressor of RE-1 silencing transcription factor (CoREST) complex as KRT19-interacting proteins. KRT19 knockout markedly enhanced histone acetylation levels. Mechanistically, KRT19 promotes CoREST complex formation by enhancing histone deacetylase 1 and REST corepressor 1 interaction, thus increasing the deacetylase activity. ChIP-seq revealed hepatocyte-specific genes, such as hepatocyte nuclear factor 4 alpha ( HNF4A ), as direct targets of KRT19-CoREST. In addition, we identified forkhead box P4 as a direct activator of aberrant KRT19 expression in liver cancer. Furthermore, treatment of primary liver tumors and patient-derived xenografts in mice suggest that KRT19 expression has the potential to predict response to histone deacetylase 1 inhibitors especially in combination with lenvatinib. CONCLUSIONS: Our data show that nuclear KRT19 acts as a transcriptional corepressor through promoting the deacetylase activity of the CoREST complex, resulting in dedifferentiation of liver cancer. These findings reveal a previously unrecognized function of KRT19 in directly shaping the epigenetic landscape in cancer.
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Intracranial fungal infection is a rare entity. This disease is mainly concentrated in dry and hot climates, such as India, Africa, California, and usually occurs in patients with immune deficiency. Now, we retrospectively analyzed the clinical manifestations, pathologic manifestations, imaging features, surgical methods, and prognosis of 4 patients with fungal infection who were confirmed by postoperative pathology. Intermittent pricking on the right face was presented in 2 patients, headache in 2 patients, orbital apex syndrome in 2 patients, and 1 patient presented with fever. Imaging showed the lesions of all patients were located in the right temporal, including 2 patients involving the right orbital, 1 patient involving the right trigeminal semilunar ganglion, 1 patient involving the right brainstem and tentorium cerebellum, 1 patient involving the right internal carotid artery. Craniotomy was performed in 2 patients, endoscopic biopsy in 1 patient, and stereotactic surgery in 1 patien. Aspergilloma was the most common pathogenic bacteria. One patient relapsed repeatedly and died. Secondary aneurysm complicated with subarachnoid hemorrhage occurred in 1 patient. Therefore, the author confirmed that intracranial fungal infection has diverse clinical, imaging, and pathologic manifestations. Neurosurgeons should be aware of the possibility of intracranial fungal infection when they find abnormal intracranial lesions, neurologic deficits, and inflammation of paranasal sinuses. Combining multiple clinical data may help doctors to improve the accuracy of diagnosis. Individualized and diversified surgical protocols should be selected for diverse lesions. Notably, secondary intracranial fungal vasculitis is common, with high mortality and disability rates.
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Microvascular decompression (MVD) has a satisfactory safety, and it is the only surgical treatment for neurovascular compression diseases, such as hemifacial spasm, trigeminal neuralgia, and glossopharyngeal neuralgia, from the perspective of etiology. Bilateral dilated and fixed pupils have long been regarded as a sign of life threatening, which is common in patients with cerebral herniation due to cranial hypertension. However, transient dilated pupils after MVD have not been previously reported. Here, we presented 2 patients with bilateral transient dilated and fixed pupils after MVD and discussed the possible etiologies through the literature review. Physical examination of both patients showed bilateral pupils were normal and without a medical history of pupil dilation. They underwent MVD under general anesthesia and used propofol and sevoflurane. In both cases, the vertebral artery was displaced, and Teflon pads were inserted between the vertebral artery and the brain stem. Postoperation, we found transient bilateral mydriasis without light reflection in both patients. The emergency head computed tomography revealed no obvious signs of hemorrhage and cerebral herniation. About 1 hour later, this phenomenon disappeared. Therefore, the authors think if MVD is successfully carried out, bilateral transient mydriasis may not necessarily indicate brain stem hemorrhage, cerebral herniation, and other emergency conditions, which can be recovered within a short time. The causes could be related to stimulation of the sympathetic pathway in the brain stem during MVD and side effects of anesthetics.
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Doenças do Nervo Glossofaríngeo , Espasmo Hemifacial , Cirurgia de Descompressão Microvascular , Midríase , Neuralgia do Trigêmeo , Humanos , Cirurgia de Descompressão Microvascular/efeitos adversos , Cirurgia de Descompressão Microvascular/métodos , Midríase/complicações , Midríase/cirurgia , Neuralgia do Trigêmeo/cirurgia , Espasmo Hemifacial/cirurgia , Doenças do Nervo Glossofaríngeo/cirurgia , Resultado do Tratamento , Estudos RetrospectivosRESUMO
Glossopharyngeal neuralgia (GPN) is an uncommon facial pain syndrome and is characterized by paroxysms of excruciating pain in the distributions of the auricular and pharyngeal branches of cranial nerves IX and X. Glossopharyngeal neuralgia characterized by otalgia alone is rare. Herein, the authors analyzed 2 patients with GPN with otalgia as the main clinical manifestation. The clinical features and prognosis of this rare group of patients with GPN were discussed. They both presented with paroxysmal pain in the external auditory meatus and preoperative magnetic resonance imaging suggested the vertebral artery were closely related to the glossopharyngeal nerves. In both patients, compression of the glossopharyngeal nerve was confirmed during microvascular decompression, and the symptoms were relieved immediately after surgery. At 11 to 15 months follow-up, there was no recurrence of pain. A variety of reasons can cause otalgia. The possibility of GPN is a clinical concern in patients with otalgia as the main complaint. The authors think the involvement of the glossopharyngeal nerve fibers in the tympanic plexus via Jacobson nerve may provide an important anatomic basis for GPN with predominant otalgia. Surface anesthesia test of the pharynx and preoperative magnetic resonance imaging is helpful for diagnosis. Microvascular decompression is effective in the treatment of GPN with predominant otalgia.
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Doenças do Nervo Glossofaríngeo , Cirurgia de Descompressão Microvascular , Humanos , Estudos Retrospectivos , Dor de Orelha/diagnóstico , Dor de Orelha/etiologia , Doenças do Nervo Glossofaríngeo/diagnóstico por imagem , Doenças do Nervo Glossofaríngeo/cirurgia , Nervo Glossofaríngeo/cirurgia , Dor/etiologia , Cirurgia de Descompressão Microvascular/efeitos adversosRESUMO
Primary hemifacial spasm (HFS) is likely related to a vascular compression of the facial nerve at its distal cisternal portion root exit Zone that has been reported during recent years. Most of these cases were found during secondary surgery or intraoperative monitoring of lateral spread response (LSR). Here we reported 2 patients with typical HFS caused by distal neurovascular compression that were successfully treated with microvascular decompression. Magnetic resonance imaging in both cases suggested that there was a contact between the vessel in cisternal segment and the facial nerve. LSR immediately disappeared after decompression of distal neurovascular compression. Resolution of spasm after the operation was achieved in both of these cases, with a short duration of vertigo and mild facial paralysis in case 1. Reviewing the literature, the majority of cases of distal neurovascular compression are found under the following 2 conditions:(1) When patients underwent a second operation. (2) When surgeons explored the distal part, the cisternal portion, after exploring the traditional root exit Zone without LSR disappearing. Therefore, it is the distal neurovascular compression at cisternal segment that may also be the cause of HFS. As for this kind of special HFS, these patients may also present with cranial nerve symptoms of VIII. In addition, magnetic resonance imaging can provide some information about compression sites. When we perform microvascular decompression, we should carefully pay attention to having an entire-root-exploration with intraoperative electrophysiology to find and decompress the real neurovascular compression.
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Espasmo Hemifacial , Cirurgia de Descompressão Microvascular , Humanos , Espasmo Hemifacial/diagnóstico por imagem , Espasmo Hemifacial/etiologia , Espasmo Hemifacial/cirurgia , Cirurgia de Descompressão Microvascular/métodos , Nervo Facial/diagnóstico por imagem , Nervo Facial/cirurgia , Monitorização Intraoperatória/métodos , PressãoRESUMO
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous priority pollutants that cause great damage to the natural environment and health. Average genome size in a community is critical for shedding light on microbiome's functional response to pollution stress within an environment. Here, microcosms under different concentrations were performed to evaluate the selection of PAHs stress on the average genome size in a community. We found the distinct communities of significantly larger genome size with the increase of PAHs concentration gradients in soils, and consistent trends were discovered in soils at different latitudes. The abundance of Proteobacteria and Deinococcus-Thermus with relatively larger genomes increased along with PAHs stress and well adapted to polluted environments. In contrast, the abundance of Patescibacteria with a highly streamlined and smaller genome decreased, implying complex interactions between environmental selection and functional fitness resulted in bacteria with larger genomes becoming more abundant. Moreover, we confirmed the increased capacity for horizontal transfer of degrading genes between communities by showing an increased connection number per node positively related to the nidA gene along the concentration gradients in the co-occurrence network. Our findings suggest PAHs tend to select bacterial taxa with larger genome sizes, with significant consequences for community stability and potential biodegradation strategies.
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Bactérias , Tamanho do Genoma , Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , Bactérias/classificação , Bactérias/metabolismo , Biodegradação Ambiental , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Microbiologia do Solo , Poluentes do Solo/análise , Poluentes do Solo/metabolismoRESUMO
As a major reservoir of antibiotics, animal manure contributes a lot to the augmented environmental pressure of antibiotic resistance genes (ARGs). This might be the first study to explore the effects of different ventilation types on the control of ARGs and to identify the relationships between archaeal communities and ARGs during the composting of dairy manure. Several ARGs were quantified via Real-time qPCR and microbial communities including bacteria and archaea were analyzed by High-throughput sequencing during vacuum-type composting (VTC) and positive-pressure composting (PPC). The total detected ARGs and class I integrase gene (intI1) under VTC were significantly lower than that under PPC during each stage of the composting (p<0.001). The relative abundance of potential human pathogenic bacteria (HPB) which were identified based on sequencing information and correlation analysis decreased by 74.6% and 91.4% at the end of PPC and VTC, respectively. The composition of archaeal communities indicated that methane-producing archaea including Methanobrevibacter, Methanocorpusculum and Methanosphaera were dominant throughout the composting. Redundancy analysis suggested that Methanobrevibacter and Methanocorpusculum were positively correlated with all of the detected ARGs. Network analysis determined that the possible hosts of ARGs were different under VTC and PPC, and provided new sights about potential links between archaea and ARGs. Our results showed better performance of VTC in reducing ARGs and potential HPB and demonstrated that some archaea could also be influential hosts of ARGs, and caution the risks of archaea carrying ARGs.
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Compostagem/métodos , Resistência Microbiana a Medicamentos/genética , Genes Arqueais , Animais , Antibacterianos , Archaea , Genes Bacterianos , Esterco , VácuoRESUMO
Over the last few decades, organic food demand has grown largely because of increasing personal health concerns. Organic farming introduces antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) into foods. However, potential effects of organic foods on the gut microbiome and ARGs have been overlooked. Using high-throughput quantitative PCR and 16S rRNA high-throughput sequencing technology, we examined 132 ARGs from major classes, eight transposase genes, universal class I integron-integrase gene (intI), clinical class I integron-integrase gene (cintI), and the bacterial community in mouse gut after 8 weeks with an either organic or inorganic lettuce and wheat diet. A total of 8 types of major ARGs and 10 mobile genetic elements (MGEs) were detected in mice gut, including tetracycline, multidrug, sulfonamide, aminoglycoside, beta-lactamase, chloramphenicol, MLSB and vancomycin resistance genes. We found that abundance and diversity of ARGs, mobile gene elements, and potential ARB in the gut increased with time after consumption of organic foods, whereas no significant changes were observed in inorganic treated groups. Moreover, MGEs, including IS613, Tp614 and tnpA_03 were found to play an important role in regulating ARG profiles in the gut microbiome following consumption of organic foods. Importantly, feeding organic food increased the relative abundance of the potentially antibiotic-resistant pathogens, Bacteroides and Streptococcus. Our results confirm that there is an increasing risk of ARGs and ARB in the gut microbiome, which highlights the importance of organic food industries taking into account the potential accumulation and transmission of ARGs as a risk factor.
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Alimentos Orgânicos , Genes Bacterianos , Animais , Camundongos , RNA Ribossômico 16S , Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Bactérias/genética , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos/genética , Integrases/genética , Integrases/farmacologiaRESUMO
BACKGROUND: Studies have shown that chemotherapy and radiotherapy can cause premature ovarian failure and loss of fertility in female cancer patients. Ovarian cortex cryopreservation is a good choice to preserve female fertility before cancer treatment. Following the remission of the disease, the thawed ovarian tissue can be transplanted back and restore fertility of the patient. However, there is a risk to reintroduce cancer cells in the body and leads to the recurrence of cancer. Given the low success rate of current in vitro culture techniques for obtaining mature oocytes from primordial follicles, an artificial ovary with primordial follicles may be a good way to solve this problem. METHODS: In the study, we established an artificial ovary model based on the participation of mesenchymal stem cells (MSCs) to evaluate the effect of MSCs on follicular development and oocyte maturation. P2.5 mouse ovaries were digested into single cell suspensions and mixed with bone marrow derived mesenchymal stem cells (BM-MSCs) at a 1:1 ratio. The reconstituted ovarian model was then generated by using phytohemagglutinin. The phenotype and mechanism studies were explored by follicle counting, immunohistochemistry, immunofluorescence, in vitro maturation (IVM), in vitro fertilization (IVF), real-time quantitative polymerase chain reaction (RT-PCR), and Terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL) assay. RESULTS: Our study found that the addition of BM-MSCs to the reconstituted ovary can enhance the survival of oocytes and promote the growth and development of follicles. After transplanting the reconstituted ovaries under kidney capsules of the recipient mice, we observed normal folliculogenesis and oocyte maturation. Interestingly, we found that BM-MSCs did not contribute to the formation of follicles in ovarian aggregation, nor did they undergo proliferation during follicle growth. Instead, the cells were found to be located around growing follicles in the reconstituted ovary. When theca cells were labeled with CYP17a1, we found some overlapped staining with green fluorescent protein(GFP)-labeled BM-MSCs. The results suggest that BM-MSCs may participate in directing the differentiation of theca layer in the reconstituted ovary. CONCLUSIONS: The presence of BM-MSCs in the artificial ovary was found to promote the survival of ovarian cells, as well as facilitate follicle formation and development. Since the cells didn't proliferate in the reconstituted ovary, this discovery suggests a potential new and safe method for the application of MSCs in clinical fertility preservation by enhancing the success rate of cryo-thawed ovarian tissues after transplantation.
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Células-Tronco Mesenquimais , Oócitos , Ovário , Feminino , Animais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Ovário/citologia , Oócitos/citologia , Oócitos/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , Folículo Ovariano/metabolismo , Folículo Ovariano/citologiaRESUMO
The worldwide elderly population is on the rise, and aging is a major osteoporosis risk factor. Senescent cells accumulation can have a detrimental effect the body as we age. The senescence-associated secretory phenotype (SASP), an essential cellular senescence hallmark, is an important mechanism connecting cellular senescence to osteoporosis. This review describes in detail the characteristics of SASPs and their regulatory agencies, and shed fresh light on how SASPs from different senescent cells contribute to osteoporosis development. Furthermore, we summarized various innovative therapy techniques that target SASPs to lower the burden of osteoporosis in the elderly and discussed the potential challenges of SASPs-based therapy for osteoporosis as a new clinical trial.
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We herein report an organic transistor functionalized with a phenylboronic acid derivative and graphene oxide for the quantification of plasma glucose levels, which has been achieved by the minimization of interferent effects derived from physical protein adsorption on the detection electrode.
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Grafite , Humanos , Eletrodos , Glucose , Plasma , Técnicas EletroquímicasRESUMO
Combined pollution caused by organic pollutants and heavy metals is common in polluted sites and wastewater. Engineering artificial microbial consortia offers a promising approach to address this complex issue. However, the mutualistic interactions and the critical function of specific microbe within microbial consortia remain unclear. In this study, based on division of labor, we respectively co-cultured two Cr(VI)-reducing strains, Paenarthrobacter nitroguajacolicus C1 and Pseudomonas putida C2, with an atrazine-degrading strain, Paenarthrobacter ureafaciens AT. After 5 days, up to 95 % Cr(VI) and 100 % atrazine were removed from the cocultures. Strain AT degraded nearly all atrazine and contributed only to a fraction of Cr(VI) reduction, whereas C1 promoted 41 % Cr(VI) transformation to Cr(III) fixed in cells, and C2 promoted 91 % Cr(VI) transformation to soluble Cr(III). Metabolic analyses of the cocultures and monocultures demonstrated that AT provided C1 with isopropylamine by passive diffusion and C2 with other effective nitrogen resources by cell-cell surface contact to promote their growth. Soil experiments also showed that treatments with AT and C2 achieved the highest Cr(VI) reduction and no atrazine residue. Our results indicate that engineering artificial microbial consortia based on division of labor and metabolic interactions is effective in promoting highly efficient bioremediation of combined pollution.
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Atrazina , Consórcios Microbianos , Atrazina/análise , Cromo/metabolismo , Biodegradação AmbientalRESUMO
Algal blooms in lakes are a major hazard worldwide. Although various geographical and environmental patterns affect algal communities during river-lake transit, a thorough understanding of what patterns shape the algal communities is still rarely researched, particularly in complex interconnected river-lake systems. In this study, focusing on the most typical interconnected river-lake system in China, the Dongting Lake, we collected paired water and sediment samples in summer, when algal biomass and growth rate are at high levels. Based on 23S rRNA gene sequencing, we investigated the heterogeneity and the differences in assembly mechanisms of planktonic and benthic algae in Dongting Lake. Planktonic algae contained more Cyanobacteria and Cryptophyta, while sediment harbored higher proportions of Bacillariophyta and Chlorophyta. For planktonic algae, stochastic dispersal dominated the assembly of the communities. Upstream rivers and confluences were important sources of planktonic algae in lakes. Meanwhile, for benthic algae, deterministic environmental filtering shaped the communities, and the proportion of benthic algae exploded with increasing N:P ratio and Cu concentration until reaching thresholds of 1.5 and 0.013 g/kg respectively, and then started falling, showing non-linear responses. This study revealed the variability of different aspects of algal communities in different habitats, traced the main sources of planktonic algae, and identified the thresholds for benthic algal shifts in response to environmental filters. Hence, upstream and downstream monitoring as well as thresholds of environmental factors should be considered in further aquatic ecological monitoring or regulatory programs of harmful algal blooms in these complex systems.
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Cianobactérias , Lagos , Lagos/microbiologia , Plâncton , Ecossistema , Eutrofização , Proliferação Nociva de Algas , China , Monitoramento AmbientalRESUMO
RATIONALE: Autoimmunity targeting glutamic acid decarboxylase 65 (GAD65) is associated with type 1 diabetes mellitus as well as various neurological diseases. In the central nervous system, GAD65 autoimmunity usually presents with limbic encephalitis, whereas extralimbic encephalitis (ELE) has only been reported in a few cases. Moreover, anti-GAD65 ELE in the paraneoplastic context has not yet been reported. PATIENT CONCERNS: A 60-year-old man presented with intermittent cough and sputum for 10 years, with no other diseases. The patient presented with recurrent seizures that were resistant to antiepileptic drugs (AEDs). Chest computed tomography and pathological results confirmed the diagnosis of small cell lung cancer. Paraneoplastic testing found a high level of GAD65 antibodies in his serum, and cerebrospinal fluid analysis revealed lymphocytic pleocytosis, indicating autoimmune encephalitis. Brain magnetic resonance imaging showed multifocal T2 fluid-attenuated inversion recovery hyperintensities in the extralimbic areas including the subcortex and deep white matter of the bilateral frontal lobe, parietal lobe, and insula lobes. DIAGNOSES: Finally, a diagnosis of anti-GAD65 autoimmune ELE with a paraneoplastic etiology from the small cell lung cancer was suspected. INTERVENTIONS: The patient refused any tumor-suppressive treatment or immunotherapy for potential side effects and only received AEDs levetiracetam, sodium valproate, and diazepam. OUTCOMES: The epilepsy of the patient was resistant to AEDs, and the patient died a week after discharge due to disease progression. LESSONS: Anti-GAD65 autoimmune encephalitis can be extralimbic, can present with isolated epilepsy, and extralimbic anti-GAD65 encephalitis can occur with an underlying malignancy.
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Doenças Autoimunes do Sistema Nervoso , Encefalite , Epilepsia , Encefalite Límbica , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Masculino , Humanos , Pessoa de Meia-Idade , Glutamato Descarboxilase , Epilepsia/terapia , Encefalite/diagnóstico , Encefalite Límbica/diagnóstico , AutoanticorposRESUMO
Soils co-contaminated with heavy metals and organic pollutants are common and threaten the natural environment and human health. Although artificial microbial consortia have advantages over single strains, the mechanism affecting their effectiveness and colonization in polluted soils still requires determination. Here, we constructed two kinds of artificial microbial consortia from the same or different phylogenetic groups and inoculated them into soil co-contaminated with Cr(VI) and atrazine to study the effects of phylogenetic distance on consortia effectiveness and colonization. The residual concentrations of pollutants demonstrated that the artificial microbial consortium from different phylogenetic groups achieved the highest removal rates of Cr(VI) and atrazine. The removal rate of 400 mg/kg atrazine was 100%, while that of 40 mg/kg Cr(VI) was 57.7%. High-throughput sequence analysis showed that the soil bacterial negative correlations, core genera, and potential metabolic interactions differed among treatments. Furthermore, artificial microbial consortia from different phylogenetic groups had better colonization and a more significant effect on the abundance of native core bacteria than consortia from the same phylogenetic group. Our study highlights the importance of phylogenetic distance on consortium effectiveness and colonization and offers insight into the bioremediation of combined pollutants.
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Atrazina , Poluentes do Solo , Humanos , Atrazina/análise , Filogenia , Consórcios Microbianos , Biodegradação Ambiental , Poluentes do Solo/metabolismo , Bactérias/genética , Bactérias/metabolismo , Solo , Microbiologia do SoloRESUMO
Radiotherapy causes DNA damage by direct ionization and indirect generation of reactive oxygen species (ROS) thereby destroying cancer cells. However, ionizing radiation (IR) unexpectedly elicits metastasis and invasion of cancer cells by inducing cancer stem cells' (CSCs) properties. As BMI1 is a crucial gene that causes radioresistance and an unfavorable prognosis of hepatocellular carcinoma (HCC), BMI1 inhibitor PTC-209 has been encapsulated in a ROS-responsive liposome (LP(PTC-209)) to be temporally and spatially delivered to radioresistant HCC tissue. The ROS generated during IR was not only considered to directly cause tumor cell death but also be used as a stimulator to trigger ROS-responsive drug release from LP(PTC-209). The PTC-209 released into resistant HCC tissue under radiotherapy further led to cancer stem cell (CSC) differentiation and then recovered radiosensitivity of HCC tumor. The suppression of the radioresistant performance of LP(PTC-209) has been proved on radiosensitive and radioresistant Hepa1-6 CSC tumor models, respectively. Our study clarified the relationship between radiotherapy and cancer stemness and provided insights to achieve complete suppression of radioresistant HCC tumor by inhibiting cancer stemness.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/radioterapia , Lipossomos/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/radioterapia , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Tolerância a Radiação , Complexo Repressor Polycomb 1/metabolismoRESUMO
Compared with the high-temperature vulcanized silicone rubber (HTVSR) insulator, the alicyclic epoxy resin insulator has higher hardness and better bonding between the core and the sheath. This makes the latter very promising in the coastal area of Southern China. Outdoor insulators are often subjected to high intensity of ultraviolet (UV)-A radiation. The influence of UV-A radiation is significant for alicyclic epoxy resin insulators. To help address the concern, the surface of two kinds of samples, namely the alicyclic epoxy resin insulator and HTVSR insulator, with UV-A aging time was characterized by tests of scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared spectroscopy (FTIR). The operation properties (mechanical properties, hydrophobicity) for outdoor insulators were also analyzed. It was found that the appearance color of the alicyclic epoxy resin has changed greatly, and there is a certain degree of fading. The mechanical properties of the alicyclic epoxy resin are maintained well and, the hydrophobicity decreases gradually. For silicone rubber, the appearance color change of silicone rubber is smaller, and the mechanical properties of silicone rubber decreased greatly. In addition, although the hydrophobicity of silicone rubber decreased gradually, it is still better than that of alicyclic epoxy resin. Both materials have broken chemical bonds, but the degree is relatively light, which meets the requirements of insulators for outdoor operation.
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Characterizing the mechanical properties of different anatomical quadrants of bones has been conducted in the literature to help understand the correlations among bone morphometric, densitometric, and material properties. However, although there are data to compare four quadrants of the long bones of the adult, there is very limited research on the young adult especially young female. Hence, nine tibia mid-shaft specimens were harvested from nine 8-week-old C57BL/6J female mice, which roughly correspond to the age range of juvenile to young adult, with one left tibia being harvested from one animal. A total of 144 indentation tests were performed with four indentations per quadrant and each of nine tibia specimens being divided into four quadrants. The Oliver and Pharr methods were used to calculate the indentation modulus and hardness. One-way ANOVA and the Kruskal-Wallis nonparametric test were used to study the influence of different anatomical quadrants on the indentation modulus and hardness. The results showed that the indentation modulus of the 8-week-old mouse tibia shaft was 18.94 ± 0.91 GPa, and the hardness was 0.51 ± 0.02 GPa. The influence of circumferential anatomical quadrants on the tibial shaft indentation modulus (p = 0.398) and hardness (p = 0.895) was not statistically significant. These methods and results could potentially help study treatments for young female long bones by comprehensively understanding the effect of treatments on four quadrants, considering collagen fiber, the degree of mineralization, and the changes of collagen cross-linking through high-resolution nanoindentation.
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Diáfises , Tíbia , Camundongos , Feminino , Animais , Camundongos Endogâmicos C57BL , Dureza , ColágenoRESUMO
Surfactant-enhanced remediation (SER) is one of the most effective methods for petroleum hydrocarbon-contaminated sites compared to single physical and chemical methods. However, biosurfactants are not as commonly used as chemical surfactants, and the actual remediation effects and related mechanisms remain undefined. Therefore, to comprehensively compare the remediation effects and biological mechanisms of biosurfactants and chemical surfactants, soil column leaching experiments including two biosurfactants (rhamnolipids and lipopeptide) and three commercially used chemical surfactants (Tween 80, Triton X-100, and Berol 226SA) were conducted. After seven days of leaching, rhamnolipids exhibited the highest petroleum hydrocarbon removal rate of 61.01%, which was superior to that of chemical surfactants (11.73-18.75%) in n-alkanes C10-C30. Meanwhile, rhamnolipids exhibited a great degradation advantage of n-alkanes C13-C28, which was 1.22-30.55 times that of chemical surfactants. Compared to chemical surfactants, biosurfactants significantly upregulated the soil's biological functions, including soil conductivity (80.90-155.56%), and soil enzyme activities of lipase (90.31-497.10%), dehydrogenase (325.00-655.56%), core enzyme activities of petroleum hydrocarbon degradation, and quorum sensing between species. Biosurfactants significantly changed the composition of Pseudomonas, Citrobacter, Acidobacteriota, and Enterobacter at the genus level. Meanwhile, chemical surfactants had less influence on the bacterial community and interactions between species. Moreover, the biosurfactants enhanced the microbial interactions and centrality of petroleum hydrocarbon degraders in the community based on the network. Overall, this work provides a systematic comparison and understanding of the chemical- and bio-surfactants used in bioremediation. In the future, we intend to apply biosurfactants to practical petroleum hydrocarbon-contaminated fields to observe realistic remediation effects and compare their functional mechanisms.