RESUMO
BACKGROUND: Haemonchus contortus (H. contortus) is the most common parasitic nematode in ruminants and is prevalent worldwide. H. contortus resistance to albendazole (ABZ) hinders the efficacy of anthelmintic drugs, but little is known about the molecular mechanisms that regulate this of drug resistance. Recent research has demonstrated that long noncoding RNAs (lncRNAs) can exert significant influence as pivotal regulators of the emergence of drug resistance. RESULTS: In this study, transcriptome sequencing was conducted on both albendazole-sensitive (ABZ-sensitive) and albendazole-resistant (ABZ-resistant) H. contortus strains, with three biological replicates for each group. The analysis of lncRNA in the transcriptomic data revealed that there were 276 differentially expressed lncRNA (DElncRNA) between strains with ABZ-sensitive and ABZ-resistant according to the criteria of |log2Foldchange|≥ 1 and FDR < 0.05. Notably, MSTRG.12969.2 and MSTRG.9827.1 exhibited the most significant upregulation and downregulation, respectively, in the resistant strains. The potential roles of the DElncRNAs included catalytic activity, stimulus response, regulation of drug metabolism, and modulation of the immune response. Moreover, we investigated the interactions between DElncRNAs and other RNAs, specifically MSTRG.12741.1, MSTRG.11848.1, MSTRG.5895.1, and MSTRG.14070.1, involved in regulating drug stimulation through cis/trans/antisense/lncRNAâmiRNA-mRNA interaction networks. This regulation leads to a decrease (or increase) in the expression of relevant genes, consequently enhancing the resistance of H. contortus to albendazole. Furthermore, through comprehensive analysis of competitive endogenous RNAs (ceRNAs) involved in drug resistance-related pathways, such as the mTOR signalling pathway and ABC transporter signalling pathway, the relevance of the MSTRG.2499.1-novel-m0062-3p-HCON_00099610 interaction was identified to mainly involve the regulation of catalytic activity, metabolism, ubiquitination and transcriptional regulation of gene promoters. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) validation indicated that the transcription profiles of six DElncRNAs and six DEmRNAs were consistent with those obtained by RNA-seq. CONCLUSIONS: The results of the present study allowed us to better understand the changes in the lncRNA expression profile of ABZ-resistant H. contortus. In total, these results suggest that the lncRNAs MSTRG.963.1, MSTRG.12741.1, MSTRG.11848.1 and MSTRG.2499.1 play important roles in the development of ABZ resistance and can serve as promising biomarkers for further study.
Assuntos
Anti-Helmínticos , Haemonchus , RNA Longo não Codificante , Animais , Albendazol/farmacologia , Albendazol/análise , Albendazol/metabolismo , Haemonchus/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transcriptoma , Anti-Helmínticos/farmacologia , Anti-Helmínticos/metabolismo , Anti-Helmínticos/uso terapêuticoRESUMO
The aim of this study was to develop an efficient strategy for enhancing H2 production in the single-chamber microbial electrolysis cell (MEC) using food waste leachate as a substrate. Different pH (8.5, 9.5, 10.5, and 11.2), applied voltage (0.8, 1.2, 1.5, 1.8, 2.0, 2.2, 2.3, and 2.4 V) and negative pressure control (-50 kPa) were tested in the single-chamber MEC. Suitable pH adjustment could greatly promote electricity generation and H2 production rather than negative pressure control. Under pH of 11.5 and 2.4 V, the maximum current density reached 121.9 ± 10.9 A/m³ with an average H2 concentration of 91.9 ± 3.2% in a 1.2-L single-chamber MEC within 30 continuous cycles of operation (â¼607 h), which was constructed with carbon brushes as the anode and stainless steel brushes as the cathode. The maximum H2 production rate reached 853.2 ± 70.3 L/m³â¢d with an H2 yield of 26.3 mmolâ¢H2/gâ¢COD. The COD removal of 68.3 ± 6.8% and three-dimensional excitation-emission matrix spectra of the effluent in the MEC within 21 ± 3h indicated efficient organics degradation in the leachate. Our results should provide a promising way to enhance the H2 production of MEC during leachate treatment.
RESUMO
Currently, computer-generated holograms (CGHs) based on ray tracing technology are generated faster and faster, and the reconstructed scenes are getting bigger and bigger and contain more and more information. Based on this situation, there are also more applications of using CGHs to hide information, but there is a lack of research on the ability to hide information. To address this issue, this paper proposes a point-sampling CGH method based on ray tracing. Our method utilizes ray tracing techniques to rapidly sample text information at different depths in the scene and hides the depth-encoded text information in the carrier image using discrete cosine transform. The reconstructed image after embedding shows good results, with a peak signal-to-noise ratio (PSNR) of 29.56 dB between the hidden images before and after embedding. The PSNR value between the embedded carrier image and the original carrier image is 51.66 dB, making it difficult for the human eye to distinguish, thereby effectively protecting the generated CGH. We also analyzed the maximum information density and observed that computational holograms obtain the maximum information density at 200×200 resolution.
RESUMO
In this study, 858 novel long non-coding RNAs (lncRNAs) were predicted as sensitive and resistant strains of Haemonchus contortus to ivermectin. These lncRNAs underwent bioinformatic analysis. In total, 205 lncRNAs significantly differed using log2 (difference multiplicity) > 1 or log2 (difference multiplicity) < - 1 and FDR < 0.05 as the threshold for significant difference analysis. We selected five lncRNAs based on significant differences in expression, cis-regulation, and their association with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. These expressions of lncRNAs, namely MSTRG.12610.1, MSTRG.8169.1, MSTRG.6355.1, MSTRG.980.1, and MSTRG.9045.1, were significantly downregulated. These findings were consistent with the results of transcriptomic sequencing. We further investigated the relative expression of target gene mRNAs and the regulation of mRNA and miRNA, starting with lncRNA cis-regulation of mRNA, and constructed a lncRNA-mRNA-miRNA network regulation. After a series of statistical analyses, we finally screened out UGT8, Unc-116, Fer-related kinase-1, GGPP synthase 1, and sart3, which may be involved in developing drug resistance under the regulation of their corresponding lncRNAs. The findings of this study provide a novel direction for future studies on drug resistance targets.
Assuntos
Resistência a Medicamentos , Haemonchus , Ivermectina , RNA Longo não Codificante , Animais , Haemonchus/genética , Haemonchus/efeitos dos fármacos , RNA Longo não Codificante/genética , Ivermectina/farmacologia , Resistência a Medicamentos/genética , Hemoncose/parasitologia , Hemoncose/veterinária , Anti-Helmínticos/farmacologia , MicroRNAs/genética , Biologia Computacional , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacosRESUMO
While pioneering methods have demonstrated that bacterial N-acyl homoserine lactone (AHL) signaling molecules can influence the growth and self-aggregation of suspended microalgae, whether AHLs can affect the initial adhesion to a carrier has remained an open question. Here we revealed that the microalgae exhibited different adhesion potential under AHL mediation, where the performance was affiliated to both AHL types and concentrations. The result can be well explained by the interaction energy theory, where the energy barrier between the carriers and the cells varied due to AHL mediation. Depth analyses revealed that AHL acted through modifying the properties of the surface electron donor of the cells, which were dependent upon three major components, i.e., extracellular protein (PN) secretion, the PN secondary structure, and the PN amino acid composition. These findings expand the known diversity of AHLs mediation on microalgal initial adhesion and metabolisms, which may interface with other major cycles and become helpful to theoretically guide the application of AHLs in microalgal culture and harvesting.
Assuntos
Acil-Butirolactonas , Microalgas , 4-Butirolactona/química , 4-Butirolactona/metabolismo , Transdução de Sinais , BiofilmesRESUMO
As a multifactor disease, the bovine respiratory disease complex (BRDC) causes high morbidity and mortality that is devastating to the cattle industry. To assess viral infections in beef cattle suffering from respiratory diseases in Inner Mongolia, 302 nasal swabs and serum samples were randomly collected from cattle with mild respiratory symptoms between March 2018 and May 2019. Our results showed that the rate of RT-PCR results positive for nucleic acids of viral pathogens in 6 cities was between 54 and 80%.The rates of bovine viral diarrhea virus (BVDV), bovine herpesvirus 1 (BHV-1), bovine parainfluenza virus type 3(BPIV3), and bovine respiratory syncytial virus(BRSV)infections were 44.70% (135/302), 24.83% (75/302), 5.63% (17/302), and 6.95% (21/302),respectively. There are also 8.94% (27/302) of samples were positive for BVDV and BHV-1, and 3.97% (12/302) of samples were positive for BPIV3 and BRSV. In addition, the RT-PCR products were sequenced, and phylogenetic analysis based on these sequences was performed. The results indicated that: a) all of the BVDV isolates were BVDV-1 and were classified as BVDV-1a (66.67%) and BVDV-1b (33.33%); b) all of the BHV-1 isolates were classified as subtype 1.1; 44.44% of the isolates were closely related to modified live viral vaccine strains, and 55.56% of the isolates were closer to epidemic strains; c) all of the BPIV3 isolates belonged to BPIV3c; d) all of the BRSV isolates were classified into subgroup III. It is suggested that an important cause of respiratory diseases for beef cattle is viral infection, and phylogenetic analysis can help us choose the proper strain to develop a vaccine.
Assuntos
Complexo Respiratório Bovino , Doenças dos Bovinos , Vírus da Diarreia Viral Bovina Tipo 1 , Vírus Sincicial Respiratório Bovino , Animais , Complexo Respiratório Bovino/epidemiologia , Bovinos , Doenças dos Bovinos/epidemiologia , China/epidemiologia , Filogenia , Vírus Sincicial Respiratório Bovino/genéticaRESUMO
The colon differs regionally in local luminal environment, excretory function, and gene expression. Polycistronic microRNA (miR)-143 and miR-145 are downregulated early in colon cancer. We asked if these microRNAs (miRNAs) might be differentially expressed in the proximal vs. the distal colon, contributing to regional differences in protein expression. Primary transcripts and mature miR-143 and miR-145 were quantified by real-time PCR, putative targets were measured by Western blotting, and DNA methylation was assessed by sequencing bisulfite-treated DNA in proximal and distal normal colonic mucosa as well as colon cancers. Putative targets of these miRNAs were assessed following transfection with miR-143 or miR-145. Mean expression of mature miR-143 and miR-145 was 2.0-fold (P < 0.001) and 1.8-fold (P = 0.03) higher, respectively, in proximal than distal colon. DNA methylation or primary transcript expression of these miRNAs did not differ by location. In agreement with increased expression of miR-143 and miR-145 in proximal colon, predicted targets of these miRNAs, apoptosis inhibitor 5 (API5), ERK5, K-RAS, and insulin receptor substrate 1 (IRS-1), which are cell cycle and survival regulators, were expressed at a lower level in proximal than distal colon. Transfection of HCA-7 colon cancer cells with miR-145 downregulated IRS-1, and transfection of HT-29 colon cancer cells with miR-143 decreased K-RAS and ERK5 expression. In conclusion, miR-143 and miR-145 and the predicted target proteins API5, ERK5, K-RAS, and IRS-1 display regional differences in expression in the colon. We speculate that differences in these tumor suppressors might contribute to regional differences in normal colonic gene expression and modulate site-specific differences in malignant predisposition.
Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Colo/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , MicroRNAs/metabolismo , Proteína Quinase 7 Ativada por Mitógeno/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas ras/metabolismo , Adulto , Ciclo Celular , Linhagem Celular Tumoral , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Proteínas Proto-Oncogênicas p21(ras) , Reação em Cadeia da Polimerase em Tempo Real/métodos , Adulto JovemRESUMO
The aim of this study was to investigate the removal of metronidazole (MNZ) from seawater using a bioelectrochemical system (BES). Single-chamber BES (i.e., S-BES) and dual-chamber BES (i.e., D-BES) were constructed with carbon brush as the anode and cathode. With the inoculum of sea mud and 2 g/L of glucose as the substrate in seawater, S-BES and D-BES were acclimated to test the MNZ removal. Results showed that S-BES could remove almost 100 % of 200 mg/L MNZ within 120 h and remain stable within 10 cycles of operation (â¼50 d) under the applied voltage of 0.8 V. The MNZ removal reached â¼100 % and 60.2 % in the cathodic and anodic chambers of D-BES fed by 100 mg/L MNZ under 0.8 V, respectively. The MNZ concentration of 200 mg/L significantly inhibited the sulfur metabolism, decreased the ratio of live to dead cells in the electrode biofilms, and thus reduced the SO42- removal in the S-BES. The MNZ degradation and S2- oxidation was mainly attributed to the cathodic and anodic biofilms of S-BES, respectively. Three degradation pathways of MNZ were proposed based on the identified intermediates and results of density functional theory calculations. The synergies among different genus species in the bacterial communities of biofilms, and between anodic and cathodic reactions could be responsible for the high performance of S-BES. Results from this study should be not only useful for the MNZ removal but also for effective MNZ inhibition of sulfate-reducing bacteria induced microbiologically influenced corrosion in seawater.
Assuntos
Ácidos Alcanossulfônicos , Bactérias , Metronidazol , Oxirredução , Eletrodos , Água do MarRESUMO
Under stress conditions, translationally stalled mRNA and associated proteins undergo liquid-liquid phase separation and condense into cytoplasmic foci called stress granules (SGs). Many viruses hijack SGs for their pathogenesis; however, whether pathogenic bacteria also exploit this pathway remains unknown. Here, we report that members of the OspC family of Shigella flexneri induce SG formation in infected cells. Mechanistically, the OspC effectors target multiple subunits of the host translation initiation factor 3 complex by ADP-riboxanation. The modification of eIF3 leads to translational arrest and thus the formation of SGs. Furthermore, OspC-mediated SGs are beneficial for S. flexneri replication within infected host cells, and bacterial strains unable to induce SGs are attenuated for virulence in a murine model of infection. Our findings reveal a mechanism by which bacterial pathogens induce SG assembly by inactivating host translational machinery and promote bacterial proliferation in host cells.
Assuntos
Fator de Iniciação 3 em Eucariotos , Shigella , Animais , Camundongos , Grânulos de Estresse , Citoplasma , Shigella flexneriRESUMO
Many researchers have realized the intelligent medical diagnosis of diabetic retinopathy (DR) from fundus images by using deep learning methods, including supervised contrastive learning (SupCon). However, although SupCon brings label information into the calculation of contrastive learning, it does not distinguish between augmented positives and same-label positives. As a result, we propose the concept of Angular Margin and incorporate it into SupCon to address this issue. To demonstrate the effectiveness of our strategy, we tested it on two datasets for the detection and grading of DR. To align with previous work, Accuracy, Precision, Recall, F1, and AUC were selected as evaluation metrics. Moreover, we also chose alignment and uniformity to verify the effect of representation learning and UMAP (Uniform Manifold Approximation and Projection) to visualize fundus image embeddings. In summary, DR detection achieved state-of-the-art results across all metrics, with Accuracy = 98.91, Precision = 98.93, Recall = 98.90, F1 = 98.91, and AUC = 99.80. The grading also attained state-of-the-art results in terms of Accuracy and AUC, which were 85.61 and 93.97, respectively. The experimental results demonstrate that Angular Margin is an excellent intelligent medical diagnostic algorithm, performing well in both DR detection and grading tasks.
RESUMO
Xenophagy is an evolutionarily conserved host defensive mechanism to eliminate invading microorganisms through autophagic machinery. The intracellular bacterial pathogen Legionella pneumophila can avoid clearance by the xenophagy pathway via the actions of multiple Dot/Icm effector proteins. Previous studies have shown that p62, an adaptor protein involved in xenophagy signaling, is excluded from Legionella-containing vacuoles (LCVs). Such defects are attributed to the multifunctional SidE family effectors (SidEs) that exhibit classic deubiquitinase (DUB) and phosphoribosyl ubiquitination (PR-ubiquitination) activities, yet the mechanism remains elusive. In the present study, we demonstrate that the host DUB USP14 is PR-ubiquitinated by SidEs at multiple serine residues, which impairs its DUB activity and its interactions with p62. The exclusion of p62 from the bacterial phagosome requires the ubiquitin ligase but not the DUB activity of SidEs. These results reveal that PR-ubiquitination of USP14 by SidEs contributes to the evasion of xenophagic clearance by L. pneumophila.
Assuntos
Legionella , Doença dos Legionários , Humanos , Legionella/metabolismo , Doença dos Legionários/metabolismo , Serina/metabolismo , Proteínas de Bactérias/metabolismo , Ubiquitinação , Ubiquitina/metabolismo , Fagossomos/metabolismo , Vacúolos/metabolismo , Ubiquitina Tiolesterase/metabolismoRESUMO
This retrospective study presents 110 patients with suspected COVID-19 vaccine-related axillary adenopathy on breast MRI. Our study aimed to assess the outcomes of axillary adenopathy detected on breast MRI performed within one year after COVID-19 vaccination. The median time between the COVID-19 vaccine and breast MRI was shorter in patients with detected adenopathy compared to patients without detected adenopathy (6 weeks [2-17] versus 15 [7-24] weeks, p < 0.001). Unilateral axillary adenopathy detected on breast MRI had a low malignancy rate (3.3%), and no cases of malignant axillary adenopathy were diagnosed without a known breast cancer in the ipsilateral breast. Our findings suggest that unilateral axillary adenopathy identified on breast MRI ipsilateral to a recent COVID-19 vaccination can be considered benign in the absence of a suspicious breast finding or known breast cancer. Regardless of vaccine status and timing, unilateral axillary adenopathy detected on MRI evaluation with a known malignancy or suspicious breast finding should be considered suspicious. This will avoid unnecessary scheduling constraints, patient anxiety, and cost, without delaying diagnosis of metastatic breast cancer.
Assuntos
Neoplasias da Mama , Vacinas contra COVID-19 , COVID-19 , Linfadenopatia , Feminino , Humanos , Axila/patologia , Neoplasias da Mama/patologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Seguimentos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Linfadenopatia/diagnóstico por imagem , Linfadenopatia/etiologia , Linfadenopatia/patologia , Metástase Linfática/patologia , Imageamento por Ressonância Magnética , Estudos Retrospectivos , VacinaçãoRESUMO
Oral propranolol has not been shown to impact physical development, such as weight and height. The impact of children's intellectual development has received relatively little attention from researchers. The effects of propranolol on the growth and development of children with proliferative infantile hemangiomas during treatment were analyzed retrospectively. The children with infantile hemangioma treated with oral propranolol in the Department of Burn and Plastic Surgery, Fuzhou Children's Hospital of Fujian Province, from February 2017 to May 2022 were analyzed. A uniform therapeutic regimen was applied, including assessment, treatment, and follow-up. The assessment included physical development and intellectual development indices. The physical development indices were height and weight. Neuropsychological assessment uses developmental quotient (DQ) to assess intelligence development. The DQs on months 3, 6, and 9 posttreatment were compared to the pretreatment. Wilcoxon rank sum test of paired samples was used for height and weight. The developmental quotient was determined by paired t test. P < .05 indicated significant difference. A total of 51 patients were enrolled. All children completed the treatment successfully, without severe adverse drug reactions leading to treatment discontinuation. There was no significant difference in height and weight before and after treatment (P > .05). No significant difference was detected in DQ 3 months posttreatment and pretreatment (P = .19), while it decreased at 6 and 9 months posttreatment (P < .05). Oral propranolol does not have an impact on physical development (height and weight). No short-term effect was found on intellectual development, but a decrease was noted over 6 months, which needs to be investigated further.
Assuntos
Hemangioma Capilar , Hemangioma , Neoplasias Cutâneas , Humanos , Criança , Lactente , Propranolol/uso terapêutico , Estudos Retrospectivos , Hemangioma/tratamento farmacológico , Resultado do Tratamento , Administração Oral , Hemangioma Capilar/tratamento farmacológico , Crescimento e Desenvolvimento , Antagonistas Adrenérgicos beta/efeitos adversos , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
Objective: Traditionally, critically ill patients requiring prolonged mechanical ventilation benefit from a long-term airway, thus necessitating tracheostomy. The widespread application of extracorporeal membrane oxygenation (ECMO) has exponentially increased in recent years, creating a new subset of patients necessitating tracheostomy with significantly increased bleeding risk. We present a hybrid dilational tracheostomy technique utilizing a Rummel tourniquet developed at our institution to mitigate bleeding risk in patients on ECMO necessitating long-term airway. Methods: A total of 24 patients on ECMO underwent bedside hybrid dilational tracheostomy with utilization of a Rummel tourniquet from 06/2020 to 01/2022 at our institution. These patients were followed longitudinally and evaluated for postoperative bleeding. Particular attention was paid to anticoagulation regimens pre- and post-operatively. Results: The primary outcome of the study, postoperative bleeding, was observed in four of the 24 study participants (16.67 %). Each of these complications were managed with tightening of the Rummel tourniquet and application of hemostatic packing agents; no operative interventions were required. Anticoagulation was held for a mean time of 4.33 h preoperatively and 5.2 h postoperatively. Conclusions: Our data support this hybrid tracheostomy technique with the addition of a Rummel tourniquet to be a safe and effective adjunct for perioperative hemostasis in high-risk patients necessitating tracheostomy while on ECMO. While this technique was initially developed for critically ill COVID-19 patients, we believe it can be applied to all patients on ECMO to help mitigate perioperative bleeding risk.
RESUMO
New therapeutic strategies for clinical Salmonella enterica serovar Typhimurium (S. Typhimurium) infection are urgently needed due to the generation of antibiotic-resistant bacteria. Inhibition of bacterial virulence has been increasingly regarded as a potential and innovative strategy for the development of anti-infection drugs. Salmonella pathogenicity island (SPI)-encoded type III secretion system (T3SS) represents a key virulence factor in S. Typhimurium, and active invasion and replication in host cells is facilitated by the secretion of T3SS effector proteins. In this study, we found that harmine could inhibit T3SS secretion; thus, its potential anti-S. Typhimurium infection activity was elucidated. Harmine inhibits the secretion and expression of T3SS effector proteins and consequently attenuates the S. Typhimurium invasion function of HeLa cells. This inhibition may be implemented by reducing the transcription of pathogenesis-related SPI-1 transcriptional activator genes hilD, hilC, and rtsA. Harmine improves the survival rate and bacterial loads of mice infected with S. Typhimurium. In summary, harmine, an effective T3SS inhibitor, could be a leading compound for the development of treatments for Salmonella infection.
Assuntos
Salmonella typhimurium , Sistemas de Secreção Tipo III , Animais , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Harmina/metabolismo , Harmina/farmacologia , Células HeLa , Humanos , Camundongos , Salmonella typhimurium/genética , Sorogrupo , Sistemas de Secreção Tipo III/metabolismo , Fatores de Virulência/metabolismoRESUMO
Background & Aims: The truncating mutations in tight junction protein 2 (TJP2) cause progressive cholestasis, liver failure, and hepatocyte carcinogenesis. Due to the lack of effective model systems, there are no targeted medications for the liver pathology with TJP2 deficiency. We leveraged the technologies of patient-specific induced pluripotent stem cells (iPSC) and CRISPR genome-editing, and we aim to establish a disease model which recapitulates phenotypes of patients with TJP2 deficiency. Methods: We differentiated iPSC to hepatocyte-like cells (iHep) on the Transwell membrane in a polarized monolayer. Immunofluorescent staining of polarity markers was detected by a confocal microscope. The epithelial barrier function and bile acid transport of bile canaliculi were quantified between the two chambers of Transwell. The morphology of bile canaliculi was measured in iHep cultured in the Matrigel sandwich system using a fluorescent probe and live-confocal imaging. Results: The iHep differentiated from iPSC with TJP2 mutations exhibited intracellular inclusions of disrupted apical membrane structures, distorted canalicular networks, altered distribution of apical and basolateral markers/transporters. The directional bile acid transport of bile canaliculi was compromised in the mutant hepatocytes, resembling the disease phenotypes observed in the liver of patients. Conclusions: Our iPSC-derived in vitro hepatocyte system revealed canalicular membrane disruption in TJP2 deficient hepatocytes and demonstrated the ability to model cholestatic disease with TJP2 deficiency to serve as a platform for further pathophysiologic study and drug discovery. Lay summary: We investigated a genetic liver disease, progressive familial intrahepatic cholestasis (PFIC), which causes severe liver disease in newborns and infants due to a lack of gene called TJP2. By using cutting-edge stem cell technology and genome editing methods, we established a novel disease modeling system in cell culture experiments. Our experiments demonstrated that the lack of TJP2 induced abnormal cell polarity and disrupted bile acid transport. These findings will lead to the subsequent investigation to further understand disease mechanisms and develop an effective treatment.
RESUMO
Salmonella enterica serovar Typhimurium (S. Typhimurium) is a zoonotic pathogen that can cause food poisoning and diarrhea in both humans and animals worldwide. The Salmonella pathogenicity island (SPI) genes encoded type III secretion system (T3SS) is important for S. Typhimurium invasion and replication in host cells. Due to the increasing problem of antibiotic resistance, antibiotic treatment for clinical Salmonella infection has gradually been limited. Anti-virulence inhibitors are a promising alternative to antibiotics because they do not easily induce bacterial antibiotic resistance. Here, we systematically evaluated the therapeutic effect of tannic acid (TA) on Salmonella-infected mice and elucidated its anti-infection mechanism. TA treatment improved the survival rate of S. Typhimurium-infected mice and alleviated cecum pathological lesions. In addition, TA inhibited S. Typhimurium invasion to HeLa cells without affecting their growth. Further studies showed that TA could inhibit the expression of sipA and sipB. This inhibition may be implemented by inhibiting the transcription of key regulatory and structural genes of the T3SS. This study provides an alternative anti-virulence strategy for Salmonella infection treatment.
RESUMO
The N-Acy-L-homoserine lactones (AHLs) mediated quorum sensing (QS) system exhibited important ecological significance in bacterial biofilm formation. However, the previous studies mainly focused on indigenous AHLs while the role of exogenous AHLs has remained unclear. This study evaluated the roles of exogenous AHLs on the biofilm formation of Pseudomonas aeruginosa. Both the C6-HSL and C8-HSL promoted the biofilm formation of P. aeruginosa with an enhancement of 2.47 and 1.88 times, respectively. Further analysis showed that exogenous AHLs contributed greatly to the adhesive ability instead of growth rate. Also, the bacterial motility and metabolic activities were significantly improved by AHLs. Moreover, the microbial functional genes (i.e. lasI, lasR, rhlI and rhlR) involved in regulating the biofilm formation were highly expressed in AHLs reactors. These findings expanded the knowledge of AHLs functions in mediating biofilm formation, and provided insightful guidance on the biofilm regulation in the wastewater treatment via biofilm technology.
Assuntos
Homosserina , Pseudomonas aeruginosa , Adesivos , Biofilmes , Percepção de QuorumRESUMO
A notable feature of the Deepwater Horizon oil spill was the unprecedented formation of marine oil snow (MOS) that was observed in large quantities floating on the sea surface and that subsequently sedimented to the seafloor. Whilst the physical and chemical processes involved in MOS formation remain unclear, some studies have shown that extracellular polymeric substances (EPS) play a role in this process. Here, we report that during exposure of subarctic northeast Atlantic seawater to a chemical dispersant, whether in the presence/absence of crude oil, the dispersant stimulates the production of significant quantities of EPS that we posit serves as a key building block in the formation of MOS. This response is likely conferred via de novo synthesis of EPS by natural communities of bacteria. We also describe the formation of marine dispersant snow (MDS) as a product of adding chemical dispersants to seawater. Differential staining confirmed that MDS, like MOS, is composed of glycoprotein, though MDS is more protein rich. Using barcoded-amplicon Illumina MiSeq sequencing, we analyzed, for the first time, the bacterial communities associated with MDS and report that their diversity is not significantly dissimilar to those associated with MOS aggregates. Our findings emphasize the need to conduct further work on the effects of dispersants when applied to oil spills at sea, particularly at different sites, and to determine how the product of this (i.e., MOS and MDS) affects the biodegradation of the oil.