ABSTRACT
This study aimed to design a standardised bronchoscopic holmium laser ablation continuous cryoablation for the treatment of airway stenosis caused by tissue hyperplasia after tracheal intubation and to retrospectively analyse its safety and feasibility. We collected the data of patients who had undergone bronchoscopic holmium laser ablation continuous cryoablation due to airway stenosis caused by tracheal mucosal tissue hyperplasia after tracheal intubation. The patients' baseline characteristics, ablation effects, surgical complications and other data were analysed. In total, 16 patients were enrolled in this study. On average, airway stenosis occurred 96.00 (interquartile range, 69.75-152.50) days after tracheal intubation and bronchoscopic holmium laser ablation continuous cryoablation took an average of 90.38 minutes (standard deviation: 16.78). After the first continuous cryoablation, 75.0% (12/16) of the patients had complete ablation of hyperplastic tissue, and 25.0% (4/16) had most of the hyperplastic tissue (>50%) removed. Altogether, 18.75% (3/16) and 6.25% (1/16) of the patients had complete ablation of hyperplastic tissue after the second and third cryoablation, respectively. Moreover, one patient (6.25%) had minimal wound bleeding postoperatively, and no other surgical complications occurred. No airway stenosis was found in all enrolled patients during follow-up 1 and 6 months after the last cryoablation. According to the above results of our small sample study indicated that bronchoscopic holmium laser ablation continuous cryoablation seems safe and effective for treating airway stenosis caused by tissue hyperplasia after tracheal intubation.
ABSTRACT
Layered iron/manganese-based oxides are a class of promising cathode materials for sustainable batteries due to their high energy densities and earth abundance. However, the stabilization of cationic and anionic redox reactions in these cathodes during cycling at high voltage remain elusive. Here, an electrochemically/thermally stable P2-Na0.67Fe0.3Mn0.5Mg0.1Ti0.1O2 cathode material with zero critical elements is designed for sodium-ion batteries (NIBs) to realize a highly reversible capacity of ≈210 mAh g-1 at 20 mA g-1 and good cycling stability with a capacity retention of 74% after 300 cycles at 200 mA g-1, even when operated with a high charge cut-off voltage of 4.5 V versus sodium metal. Combining a suite of cutting-edge characterizations and computational modeling, it is shown that Mg/Ti co-doping leads to stabilized surface/bulk structure at high voltage and high temperature, and more importantly, enhances cationic/anionic redox reaction reversibility over extended cycles with the suppression of other undesired oxygen activities. This work fundamentally deepens the failure mechanism of Fe/Mn-based layered cathodes and highlights the importance of dopant engineering to achieve high-energy and earth-abundant cathode material for sustainable and long-lasting NIBs.
ABSTRACT
Karrikins and strigolactones govern plant development and environmental responses through closely related signaling pathways. The transcriptional repressor proteins SUPPRESSOR OF MAX2 1 (SMAX1), SMAX1-like2 (SMXL2), and D53-like SMXLs mediate karrikin and strigolactone signaling by directly binding downstream genes or by inhibiting the activities of transcription factors. In this study, we characterized the non-transcriptional regulatory activities of SMXL proteins in Arabidopsis. We discovered that SMAX1 and SMXL2 with mutations in their ethylene-response factor-associated amphiphilic repression (EAR) motif had undetectable or weak transcriptional repression activities but still partially rescued the hypocotyl elongation defects and fully reversed the cotyledon epinasty defects of the smax1 smxl2 mutant. SMAX1 and SMXL2 directly interact with PHYTOCHROME INTERACTION FACTOR 4 (PIF4) and PIF5 to enhance their protein stability by interacting with phytochrome B (phyB) and suppressing the association of phyB with PIF4 and PIF5. The karrikin-responsive genes were then identified by treatment with GR24ent-5DS, a GR24 analog showing karrikin activity. Interestingly, INDOLE-3-ACETIC ACID INDUCIBLE 29 (IAA29) expression was repressed by GR24ent-5DS treatment in a PIF4- and PIF5-dependent and EAR-independent manner, whereas KARRIKIN UPREGULATED F-BOX 1 (KUF1) expression was induced in a PIF4- and PIF5-independent and EAR-dependent manner. Furthermore, the non-transcriptional regulatory activity of SMAX1, which is independent of the EAR motif, had a global effect on gene expression. Taken together, these results indicate that non-transcriptional regulatory activities of SMAX1 and SMXL2 mediate karrikin-regulated seedling response to red light.
Subject(s)
Arabidopsis Proteins , Arabidopsis , Furans , Gene Expression Regulation, Plant , Light , Seedlings , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis/radiation effects , Arabidopsis Proteins/metabolism , Arabidopsis Proteins/genetics , Seedlings/genetics , Seedlings/radiation effects , Seedlings/growth & development , Seedlings/metabolism , Gene Expression Regulation, Plant/radiation effects , Furans/pharmacology , Furans/metabolism , Pyrans/pharmacology , Pyrans/metabolism , Repressor Proteins/metabolism , Repressor Proteins/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , Basic Helix-Loop-Helix Transcription Factors/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , Hypocotyl/genetics , Hypocotyl/growth & development , Hypocotyl/metabolism , Mutation , Red Light , Intracellular Signaling Peptides and ProteinsABSTRACT
Polymyxins are a last-resort treatment option for multidrug-resistant gram-negative bacterial infections, but they are associated with nephrotoxicity. Gelofusine was previously shown to reduce polymyxin-associated kidney injury in an animal model. However, the mechanism(s) of renal protection has not been fully elucidated. Here, we report the use of a cell culture model to provide insights into the mechanisms of renal protection. Murine epithelial proximal tubular cells were exposed to polymyxin B. Cell viability, lactate dehydrogenase (LDH) release, polymyxin B uptake, mitochondrial superoxide production, nuclear morphology, and apoptosis activation were evaluated with or without concomitant gelofusine. A megalin knockout cell line was used as an uptake inhibition control. Methionine was included in selected experiments as an antioxidant control. A polymyxin B concentration-dependent reduction in cell viability was observed. Increased viability was observed in megalin knockout cells following comparable polymyxin B exposures. Compared with polymyxin B exposure alone, concomitant gelofusine significantly increased cell viability as well as reduced LDH release, polymyxin B uptake, mitochondrial superoxide, and apoptosis. Gelofusine and methionine were more effective at reducing renal cell injury in combination than either agent alone. In conclusion, the mechanisms of renal protection by gelofusine involve decreasing cellular drug uptake, reducing subsequent oxidative stress and apoptosis activation. These findings would be valuable for translational research into clinical strategies to attenuate drug-associated acute kidney injury.NEW & NOTEWORTHY Gelofusine is a gelatinous saline solution with the potential to attenuate polymyxin-associated nephrotoxicity. We demonstrated that the mechanisms of gelofusine renal protection involve reducing polymyxin B uptake by proximal tubule cells, limiting subsequent oxidative stress and apoptosis activation. In addition, gelofusine was more effective at reducing cellular injury than a known antioxidant control, methionine, and a megalin knockout cell line, indicating that gelofusine likely has additional pharmacological properties besides only megalin inhibition.
Subject(s)
Anti-Bacterial Agents , Apoptosis , Polymyxin B , Animals , Polymyxin B/pharmacology , Mice , Apoptosis/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/toxicity , Cell Survival/drug effects , Kidney Tubules, Proximal/metabolism , Kidney Tubules, Proximal/drug effects , Kidney Tubules, Proximal/pathology , Cell Line , Low Density Lipoprotein Receptor-Related Protein-2/metabolism , Low Density Lipoprotein Receptor-Related Protein-2/genetics , Acute Kidney Injury/metabolism , Acute Kidney Injury/pathology , Acute Kidney Injury/prevention & control , Acute Kidney Injury/chemically induced , Oxidative Stress/drug effects , L-Lactate Dehydrogenase/metabolismABSTRACT
BACKGROUND: Glucocorticoids have been widely used in perioperative period for postoperative pain relief after total knee arthroplasty (TKA). However, the optimal administration protocols of glucocorticoids remain controversial. This study aims to compare the efficacy of glucocorticoids between intravenous and periarticular injection on clinical outcomes. METHODS: A total of 114 patients were randomly assigned to intravenous (IV) group (n = 57) and periarticular injection (PI) group (n = 57). The IV group received 10 mg dexamethasone intravenously and the PI group received periarticular injection of 10 mg dexamethasone during the procedure. The clinical outcomes were assessed using visual analogue scale (VAS), knee society score (KSS), range of motion (ROM), knee swelling, inflammation markers and complications after TKA. RESULTS: The VAS score during walking at 2nd day postoperatively was lower in the PI group compared with the IV group (2.08 ± 1.45 vs 2.73 ± 1.69, p = .039), and there was no significant difference at the other time points of VAS score in two groups. The inflammation markers, knee swelling, knee ROM and KSS score were not statistically different. Vomiting and other complications occurrence were not significantly different between the two groups. CONCLUSIONS: Intraoperative periarticular injection of glucocorticoids has similar analgesic effect compared to intravenous in the postoperative period following TKA and may be even more effective on the second postoperative day. In addition, periarticular injection of glucocorticoids does not impose an excess risk or complication on patients.
Subject(s)
Arthroplasty, Replacement, Knee , Dexamethasone , Glucocorticoids , Pain, Postoperative , Humans , Arthroplasty, Replacement, Knee/adverse effects , Male , Glucocorticoids/administration & dosage , Female , Injections, Intra-Articular , Aged , Prospective Studies , Middle Aged , Pain, Postoperative/drug therapy , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Pain, Postoperative/diagnosis , Dexamethasone/administration & dosage , Injections, Intravenous , Pain Measurement , Intraoperative Care/methods , Treatment Outcome , Range of Motion, ArticularABSTRACT
Staphylococcus aureus (S. aureus) pneumonia has become an increasingly important public health problem. Recent evidence suggests that epigenetic modifications are critical in the host immune defence against pathogen infection. In this study, we found that S. aureus infection induces the expression of histone deacetylase 6 (HDAC6) in a dose-dependent manner. Furthermore, by using a S. aureus pneumonia mouse model, we showed that the HDAC6 inhibitor, tubastatin A, demonstrates a protective effect in S. aureus pneumonia, decreasing the mortality and destruction of lung architecture, reducing the bacterial burden in the lungs and inhibiting inflammatory responses. Mechanistic studies in primary bone marrow-derived macrophages demonstrated that the HDAC6 inhibitors, tubastatin A and tubacin, reduced the intracellular bacterial load by promoting bacterial clearance rather than regulating phagocytosis. Finally, N-acetyl-L- cysteine, a widely used reactive oxygen species (ROS) scavenger, antagonized ROS production and significantly inhibited tubastatin A-induced S. aureus clearance. These findings demonstrate that HDAC6 inhibitors promote the bactericidal activity of macrophages by inducing ROS, an important host factor for S. aureus clearance and production. Our study identified HDAC6 as a suitable epigenetic modification target for preventing S. aureus infection, and tubastatin A as a useful compound in treating S. aureus pneumonia.
Subject(s)
Histone Deacetylase 6 , Histone Deacetylase Inhibitors , Macrophages , Reactive Oxygen Species , Staphylococcus aureus , Animals , Histone Deacetylase 6/antagonists & inhibitors , Histone Deacetylase 6/metabolism , Reactive Oxygen Species/metabolism , Staphylococcus aureus/drug effects , Mice , Macrophages/drug effects , Macrophages/metabolism , Macrophages/microbiology , Histone Deacetylase Inhibitors/pharmacology , Hydroxamic Acids/pharmacology , Pneumonia, Staphylococcal/drug therapy , Pneumonia, Staphylococcal/microbiology , Pneumonia, Staphylococcal/metabolism , Indoles/pharmacology , Mice, Inbred C57BL , Phagocytosis/drug effects , Lung/drug effects , Lung/microbiology , Lung/metabolism , Lung/pathologyABSTRACT
OBJECTIVE: To conduct molecular prevalence and genetic polymorphism analysis of 24 Swine Farm associated C. difficile ST11 strains, in addition to other representative sequenced ST strains. METHODS: The collected C. difficile strains underwent whole genome sequencing and bioinformatic analysis using the illumina NovaSeq platform, SPAdes, Prokka, MOB-suite, and FastTree. Virulence and antibiotic resistance genes were identified through NCBI Pathogen Database. Cytotoxicity tests were conducted on HT-29 cells and Vero cells to verify the function of toxin A and toxin B. RESULTS: The most prevalent resistance genes in ST11 were found to be against ß-lactamases, aminoglycosides, and tetracycline. A C. difficile isolate (strain 27) with tcdA deletion and high antibiotic resistance genes was far apart from other swine farm associated ST11 isolates in the phylogenetic branch. The remarkable genetic similarity between animal and human C. difficile strains suggests potential transmission of ST11 strains between animals and humans. The plasmid replicon sequences repUS43 were identified in all ST11 strains except one variant (strain 27), and 91.67% (22/24) of these were assessed by MOB-typer as having mobilizable plasmids. CONCLUSION: Swine farm associated C. difficile ST11 carried fewer virulence genes than ST11 strains collected from NCBI database. It is critical to monitor the evolution of C. difficile strains to understand their changing characteristics, host-switching, and develop effective control and prevention strategies.
Subject(s)
Clostridioides difficile , Clostridium Infections , Farms , Phylogeny , Swine Diseases , Animals , Clostridioides difficile/genetics , Clostridioides difficile/classification , Swine , Swine Diseases/microbiology , Swine Diseases/epidemiology , Clostridium Infections/veterinary , Clostridium Infections/microbiology , Clostridium Infections/epidemiology , Whole Genome Sequencing , Anti-Bacterial Agents/pharmacology , Virulence/genetics , Vero Cells , Humans , Chlorocebus aethiops , Drug Resistance, Bacterial/genetics , Plasmids/genetics , Virulence Factors/geneticsABSTRACT
T-bet, encoded by TBX21, is extensively expressed across various immune cell types, and orchestrates critical functions in their development, survival, and physiological activities. However, the role of T-bet in non-immune compartments, notably the epithelial cells, remains obscure. Herein, a Tet-O-T-bet transgenic mouse strain is generated for doxycycline-inducible T-bet expression in adult animals. Unexpectedly, ubiquitous T-bet overexpression causes acute diarrhea, intestinal damage, and rapid mortality. Cell-type-specific analyses reveal that T-bet-driven pathology is not attributable to its overexpression in CD4+ T cells or myeloid lineages. Instead, inducible T-bet overexpression in the intestinal epithelial cells is the critical determinant of the observed lethal phenotype. Mechanistically, T-bet overexpression modulates ion channel and transporter profiles in gut epithelial cells, triggering profound fluid secretion and subsequent lethal dehydration. Furthermore, ectopic T-bet expression enhances gut epithelial cell apoptosis and markedly suppresses colon cancer development in xenograft models. Collectively, the findings unveil a previously unrecognized role of T-bet in intestinal epithelial cells for inducing apoptosis, diarrhea, and local inflammation, thus implicating its potential as a therapeutic target for the treatment of cancer and inflammatory diseases.
Subject(s)
Apoptosis , Epithelial Cells , Ion Channels , Mice, Transgenic , T-Box Domain Proteins , Animals , Mice , Apoptosis/genetics , T-Box Domain Proteins/metabolism , T-Box Domain Proteins/genetics , Ion Channels/metabolism , Ion Channels/genetics , Epithelial Cells/metabolism , Intestinal Mucosa/metabolism , Humans , Disease Models, AnimalABSTRACT
Hormone-activated proteolysis is a recurring theme of plant hormone signaling mechanisms. In strigolactone signaling, the enzyme receptor DWARF14 (D14) and an F-box protein, MORE AXILLARY GROWTH2 (MAX2), mark SUPPRESSOR OF MAX2 1-LIKE (SMXL) family proteins SMXL6, SMXL7, and SMXL8 for rapid degradation. Removal of these transcriptional corepressors initiates downstream growth responses. The homologous proteins SMXL3, SMXL4, and SMXL5, however, are resistant to MAX2-mediated degradation. We discovered that the smxl4 smxl5 mutant has enhanced responses to strigolactone. SMXL5 attenuates strigolactone signaling by interfering with AtD14-SMXL7 interactions. SMXL5 interacts with AtD14 and SMXL7, providing two possible ways to inhibit SMXL7 degradation. SMXL5 function is partially dependent on an ethylene-responsive-element binding-factor-associated amphiphilic repression (EAR) motif, which typically mediates interactions with the TOPLESS family of transcriptional corepressors. However, we found that loss of the EAR motif reduces SMXL5-SMXL7 interactions and the attenuation of strigolactone signaling by SMXL5. We hypothesize that integration of SMXL5 into heteromeric SMXL complexes reduces the susceptibility of SMXL6/7/8 proteins to strigolactone-activated degradation and that the EAR motif promotes the formation or stability of these complexes. This mechanism may provide a way to spatially or temporally fine-tune strigolactone signaling through the regulation of SMXL5 expression or translation.
Subject(s)
Arabidopsis Proteins , Arabidopsis , Heterocyclic Compounds, 3-Ring , Arabidopsis/metabolism , Arabidopsis Proteins/metabolism , Lactones/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Co-Repressor Proteins/metabolism , Gene Expression Regulation, PlantABSTRACT
Carbapenem-resistant Escherichia coli (CREC) poses a severe global public health risk. This study reveals the worldwide geographic spreading patterns and spatiotemporal distribution characteristics of resistance genes in 7918 CREC isolates belonging to 497 sequence types (ST) and originating from 75 countries. In the last decade, there has been a transition in the prevailing STs from highly virulent ST131 and ST38 to higher antibiotic-resistant ST410 and ST167. The rise of multi-drug resistant strains of CREC carrying plasmids with extended-spectrum beta-lactamase (ESBL) resistance genes could be attributed to three important instances of host-switching events. The spread of CREC was associated with the changing trends in blaNDM-5, blaKPC-2, and blaOXA-48, as well as the plasmids IncFI, IncFII, and IncI. There were intercontinental geographic transfers of major CREC strains. Various crucial transmission hubs and patterns have been identified for ST131 in the United Kingdom, Italy, the United States, and China, ST167 in India, France, Egypt, and the United States, and ST410 in Thailand, Israel, the United Kingdom, France, and the United States. This work is valuable in managing CREC infections and preventing CREC occurrence and transmission inside healthcare settings and among diverse hosts.
Subject(s)
Carbapenem-Resistant Enterobacteriaceae , Escherichia coli/genetics , Public Health , Anti-Bacterial Agents , Carbapenems/pharmacologyABSTRACT
Ventilator-associated pneumonia (VAP) and pyogenic liver abscess (PLA) due to Klebsiella pneumoniae infection can trigger life-threatening malignant consequences, however, there are few studies on the strain-associated clinical pathogenic mechanisms between VAP and PLA. A total of 266 patients consist of 129 VAP and 137 PLA were included for analysis in this study. We conducted a comprehensive survey for the two groups of K. pneumoniae isolates, including phenotypic experiments, clinical epidemiology, genomic analysis, and instrumental analysis, i.e., to obtain the genomic differential profile of K. pneumoniae strains responsible for two distinct infection outcomes. We found that PLA group had a propensity for specific underlying diseases, especially diabetes and cholelithiasis. The resistance level of VAP was significantly higher than that of PLA (78.57% vs. 36%, P < 0.001), while the virulence results were opposite. There were also some differences in key signaling pathways of biochemical processes between the two groups. The combination of iucA, rmpA, hypermucoviscous phenotype, and ST23 presented in K. pneumoniae infection is more important and highly prudent for timely treatment. The present study may contribute a benchmark for the K. pneumoniae clinical screening, epidemiological surveillance, and effective therapeutic strategies.
Subject(s)
Klebsiella Infections , Liver Abscess , Pneumonia, Ventilator-Associated , Humans , Klebsiella pneumoniae , Virulence Factors/genetics , Multilocus Sequence Typing , Phenotype , Klebsiella Infections/epidemiologyABSTRACT
BACKGROUND: Adolescent aggression has long been of interest to researchers. However, few studies have examined the influencing factors and mechanisms of aggression among violent juvenile offenders. This study tests a moderated mediation model with Chinese male violent juvenile offenders as subjects. Specifically, it explores the relationship between early adversity and aggression, as well as the mechanisms of life history strategy and meaning in life in this relationship. METHODS: A total of 537 Chinese male violent juvenile offenders completed the Childhood Environment Scale, the Life History Strategy Short Form Scale, the Aggression Questionnaire, and the Meaning in Life Questionnaire. After controlling for socioeconomic status (SES), the current cross-sectional study used structural equation modeling (SEM) to examine a moderated mediation model. RESULTS: The results showed that life history strategy mediated the relationship between early adversity and aggression, and early adversity affected individuals' aggression by accelerating their life history strategies. The results also showed that meaning in life moderated the relationship between early adversity and life history strategy. For individuals with high meaning in life scores, the negative predictive effect of early adversity on life history strategy was stronger than that for individuals with low meaning in life scores. CONCLUSION: The results of this study can advance the understanding of how early adversity affects aggression among violent juvenile offenders and provide theoretical support for prison staff to develop educational strategies and subsequent interventions.
Subject(s)
Criminals , Life History Traits , Adolescent , Humans , Male , Child , Violence , Cross-Sectional Studies , East Asian People , AggressionABSTRACT
Staphylococcus aureus (S. aureus) is a major cause of foodborne infections and its persistence in raw milk is a multifaceted phenomenon that poses a considerable public health challenge. Our study investigated the prevalence, virulence genes, antibiotic resistance, and genetic characterization of S. aureus in raw milk in six Shanghai districts from 2013 to 2022. At 18 dairy farms, a total of 704 S. aureus strains were isolated from 1799 samples tested for drug sensitivity. The highest rates of antibiotic resistance were ampicillin (96.7 %), sulfamethoxazole (65 %), and erythromycin (21.6 %). Between 2018 and 2022, there was a significant decrease in the resistance rates of ceftiofur, ofloxacin, tilmicosin, erythromycin, clindamycin, amoxicillin-clavulanic acid, and sulfamethoxazole in comparison to the period from 2013 to 2017. There were 205 S. aureus strains chosen for whole genome sequencing (WGS), with no more than 2 strains of the same resistance phenotype from each farm per year. The prevalence of mecA-positive strains was 14.15 %, while other antibiotic resistance-associated genes were observed as follows: blaI (70.21 %), lnu(B) (5.85 %), lsa(E) (5.75 %), fexA (6.83 %), erm(C) (4.39 %), tet(L) (9.27 %), and dfrG (5.85 %). Isolates harboring the immune evasion cluster (IEC) genes (scn, chp, and sak) were predominantly categorized as sequence types (STs) 7, 188, 15, 59, and 398. The predominant cluster complexes were CC97, CC1, CC398, and CC1651. In 2017-2022, there was a transition in CC1 from the highly antibiotic-resistant ST9 strain that emerged between 2013 and 2018 to the low-resistant but highly virulent ST1 strain. Retrospective phylogenetic analysis elucidated the evolutionary history of the isolates and demonstrated that the human-animal host transition of S. aureus was linked to the genesis of MRSA CC398. The implementation of extended surveillance will aid in the development of innovative strategies to avoid the transmission of S. aureus along the dairy food chain and the occurrence of public health events.
Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Animals , Humans , Staphylococcus aureus/genetics , Virulence/genetics , Milk , Phylogeny , Retrospective Studies , China , Staphylococcal Infections/epidemiology , Staphylococcal Infections/veterinary , Anti-Bacterial Agents/pharmacology , Erythromycin , Drug Resistance, Microbial , Sulfamethoxazole , Genetic Variation , Methicillin-Resistant Staphylococcus aureus/genetics , Microbial Sensitivity TestsABSTRACT
Semiconductor lasers with delayed optical feedback are a promising source of optical chaos for practical applications, owing to simple configurations that are easy to integrate and synchronize. However, for traditional semiconductor lasers, the chaos bandwidth is limited by the relaxation frequency to several gigahertz. Here, we propose and experimentally demonstrate that a short-resonant-cavity distributed-feedback (SC-DFB) laser can generate broadband chaos only with simple feedback from an external mirror. The short distributed-feedback resonant cavity not only enhances laser relaxation frequency but also makes the laser mode more susceptible to external feedback. Experiments obtained a laser chaos with 33.6â GHz bandwidth and a spectral flatness of 4.5â dB. The corresponding entropy rate is estimated as more than 33.3â Gbit/s. It is believed that the SC-DFB lasers will promote development of chaos-based secure communication and physical key distribution.
Subject(s)
Lasers, Semiconductor , Light , Feedback , Entropy , Equipment DesignABSTRACT
Bacteriophages (phages) are nanostructured viruses with highly selective antibacterial properties that have gained attention beyond eliminating bacteria. Specifically, M13 phages are filamentous phages that have recently been studied in various aspects of nanomedicine due to their biological advantages and more compliant engineering capabilities over other phages. Having nanofiber-like morphology, M13 phages can reach varied target sites and self-assemble into multidimensional scaffolds in a relatively safe and stable way. In addition, genetic modification of the coat proteins enables specific display of peptides and antibodies on the phages, allowing for precise and individualized medicine. M13 phages have also been subjected to novel engineering approaches, including phage-based bionanomaterial engineering and phage-directed nanomaterial combinations that enhance the bionanomaterial properties of M13 phages. In view of these features, researchers have been able to utilize M13 phages for therapeutic applications such as drug delivery, biodetection, tissue regeneration, and targeted cancer therapy. In particular, M13 phages have been utilized as a novel bionanomaterial for precisely mimicking natural tissue environment in order to overcome the shortage in tissue and organ donors. Hence, in this review, we address the recent studies and advances of using M13 phages in the field of nanomedicine as therapeutic agents based upon their characteristics as novel bionanomaterial with biomolecules displayed. This paper also emphasizes the novel engineering approach that enhances M13 phage's bionanomaterial capabilities. Current limitations and future approaches are also discussed to provide insight in further progress for M13 phage-based clinical applications.
ABSTRACT
With increasing attention paid to the concept of the microbiota-gut-brain axis, mounting evidence reveals that the gut microbiota is involved in a variety of neurological and psychiatric diseases. However, gut microbiota changes in major depressive disorder (MDD) patients and their association with disease mechanisms remain undefined. Fifty MDD patients and sixty healthy controls were recruited from the Shanghai Healthy Mental Center, China. Fecal samples were collected, and the compositional characteristics of the intestinal flora were determined in MDD patients by MiSeq sequencing. Venous blood was collected for the detection of plasma indoleamine-2,3-dioxygenase (Ido), kynurenine (Kyn) and tryptophan (Trp) levels. Stool samples of bacterial 16S sequencing was carried out. A total of 2,705,809 optimized sequences were obtained, with an average of 54,116 per sample. More unique OTUs were observed at the family, genus and species levels in the control group compared with the MDD cases. Further analysis showed significant changes in the α- and ß-diversities and relative abundance levels of gut microbial entities in MDD patients, as well as elevated amounts of Ido and Kyn indicating Kyn pathway activation, KEGG bacterial 16S function prediction analysis shows a variety of amino acids and metabolic (including Ido, Trp and Kyn) changes in the body of patients with MDD. These may result in increased neurotoxic metabolites and reduced generation of serotonin in the disease process. These changed factors may potentially be utilized as biomarkers for MDD in the future, playing more important roles in the disease course.
Subject(s)
Depressive Disorder, Major , Gastrointestinal Microbiome , Humans , Kynurenine/metabolism , Depressive Disorder, Major/psychology , Dysbiosis , China , Tryptophan/metabolism , BiomarkersABSTRACT
BACKGROUND: Based on its objective characteristics, laboratory markers have always been the research direction of clinical diagnosis and assessment of mental disorders including Alzheimer's disease. METHODS: MTT Colorimetric Assay, ELISA, and quantitative PCR were used to investigate the responsiveness of peripheral blood mononuclear cells (PBMCs) to mitogen Lipopolysaccharides (LPS) and Phytohemagglutinin (PHA), PBMCs genomic methylation and hydroxymethylation levels, nuclear DNA and mitochondrial DNA damage, respiratory chain enzyme activities, and circulating cell-free mitochondrial DNA levels were detected in 90 patients with Alzheimer's disease. RESULTS: In the Alzheimer's disease group, LPS stimulated PBMCs viability, TNF-α secretion, PHA stimulated IL-10 secretion, genomic DNA methylation levels, circulating cell-free mitochondrial DNA copies, citrate synthase activity were reduced compared to the control; while the LPS stimulated PBMCs IL-1α secretion, PHA stimulated IL-1α and IFN-γ secretion, plasma IL-6 and TNF-α, mitochondrial DNA damages were increased compared to the control. CONCLUSIONS: The reactivity of peripheral blood mononuclear cells to mitogens, mitochondrial DNA integrity characteristics, and cell-free mitochondrial DNA copies may be used as candidate laboratory biomarkers to help clinical management of Alzheimer's disease.
Subject(s)
Alzheimer Disease , Mitogens , Humans , Mitogens/pharmacology , Lipopolysaccharides , Leukocytes, Mononuclear , Tumor Necrosis Factor-alpha , Cytokines , DNA, Mitochondrial , Alzheimer Disease/diagnosis , Phytohemagglutinins/pharmacologyABSTRACT
Abiotic stress is one of the most important factors reducing soybean yield. It is essential to identify regulatory factors contributing to stress responses. A previous study found that the tandem CCCH zinc-finger protein GmZF351 is an oil level regulator. In this study, we discovered that the GmZF351 gene is induced by stress and that the overexpression of GmZF351 confers stress tolerance to transgenic soybean. GmZF351 directly regulates the expression of GmCIPK9 and GmSnRK, leading to stomata closing, by binding to their promoter regions, which carry two CT(G/C)(T/A)AA elements. Stress induction of GmZF351 is mediated through reduction in the H3K27me3 level at the GmZF351 locus. Two JMJ30-demethylase-like genes, GmJMJ30-1 and GmJMJ30-2, are involved in this demethylation process. Overexpression of GmJMJ30-1/2 in transgenic hairy roots enhances GmZF351 expression mediated by histone demethylation and confers stress tolerance to soybean. Yield-related agronomic traits were evaluated in stable GmZF351-transgenic plants under mild drought stress conditions. Our study reveals a new mode of GmJMJ30-GmZF351 action in stress tolerance, in addition to that of GmZF351 in oil accumulation. Manipulation of the components in this pathway is expected to improve soybean traits and adaptation under unfavorable environments.
Subject(s)
Droughts , Glycine max , Glycine max/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Sodium Chloride/pharmacology , Plants, Genetically Modified/metabolism , Stress, Physiological , Zinc/metabolism , Gene Expression Regulation, PlantABSTRACT
[This corrects the article DOI: 10.1371/journal.pgen.1004524.].
ABSTRACT
OBJECTIVE: The current study aims to investigate the factors that could predict response to intra-articular corticosteroid injection (IACI) in patients with knee osteoarthritis (KOA). METHODS: Data of participants were retrieved from the Osteoarthritis Initiative database. Participants with at least one IACI treatment on single or bilateral knees within the first 5 years of follow-up were retrospectively included. Demographic data, clinical and radiographic variables were collected at both baseline and the first follow-up after IACI treatment. Positive response to IACI treatment was defined as >20% reduction of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score from V0 to V1. All the variables with P < 0.2 after the comparison between the response and non-response groups were included in a multivariable logistic regression model to identify independent response predictive patient-specific valuables. Receiver operating characteristic curves were performed to establish the cutoff values of independent predictors. RESULTS: The current study included a total of 385 participants (473 knees), with 155 and 318 knees classified into the response group and non-response group, respectively. Those with satisfied responses to IACI treatment had significantly higher WOMAC pain score (P < 0.001), disability score (P = 0.002), and stiffness score (P = 0.015) at the baseline. Baseline WOMAC pain score showed significant association with positive response to IACI treatment in multivariate logistic analysis and the best cutoff value was 5 points. The rate of analgesics utilization was lower (P = 0.014) in the response group than the non-response group after the IACI treatment. CONCLUSION: KOA patients with a baseline WOMAC pain score ≥5 are more likely to benefit from IACI treatment.