ABSTRACT
The objective of this study was to explore the effects of cold atmospheric plasma (CAP) treatment on the biological behavior of human gingival fibroblasts (HGFs) cultured on the surface of high-transparency zirconia. Two types of zirconia, 3Y-ZTP and 4Y-PSZ, were subjected to a CAP treatment for various treatment durations. Analyses of the physical and chemical properties of 3Y-ZTP and 4Y-PSZ were conducted using scanning electron microscopy, contact angle measurements, and X-ray photoelectron spectroscopy, both before and after CAP treatment. The biological responses of HGFs on both surfaces were assessed using CCK-8 assay, confocal laser scanning microscopy, and real-time PCR. Initially, the oxygen and hydroxyl contents on the surface of 4Y-PSZ exceeded those on 3Y-ZTP. CAP treatment enhanced the surface hydrophilicity and the reactive oxygen species (ROS) content of 4Y-PSZ, while not altering the surface morphology. After CAP treatment, HGFs' adhesion on 4Y-PSZ was superior, with more pronounced effects compared to 3Y-ZTP. Notably, HGFs counts and the expression of adhesion-related genes on 4Y-PSZ peaked following the CAP exposures for 30 s and 60 s. Consequently, this study demonstrates that, following identical CAP treatments, 4Y-PSZ is more effective in promoting HGFs adhesion compared to traditional 3Y-ZTP zirconia.
ABSTRACT
Feline bocavirus (FBoV) is a globally distributed linear, single-stranded DNA virus infect cats, currently classified into three distinct genotypes. Although FBoV can lead to systemic infections, its complete pathogenic potential remains unclear. In this study, 289 blood samples were collected from healthy cats in Harbin, revealing an overall FBoV prevalence of 12.1%. Notably, genotypes 1 and 3 of FBoV were found co-circulating among the cat population in Harbin. Additionally, recombination events were detected, particularly in the newly discovered NG/104 and DL/102 strains. Furthermore, negative selection sites were predominantly observed across the protein coding genes of FBoV. These findings suggest a co-circulation of genetically diverse FBoV strains among cats in Harbin, indicate that purifying selection is the primary driving force shaping the genomic evolution of FBoV, and also underscore the importance of comprehensive surveillance efforts to enhance our understanding of the epidemiology and evolutionary characteristics of FBoV.
Subject(s)
Bocavirus , Cat Diseases , Genetic Variation , Genotype , Parvoviridae Infections , Phylogeny , Cats , Animals , China/epidemiology , Cat Diseases/virology , Cat Diseases/epidemiology , Parvoviridae Infections/veterinary , Parvoviridae Infections/virology , Parvoviridae Infections/epidemiology , Bocavirus/genetics , Bocavirus/classification , Bocavirus/isolation & purification , Prevalence , Recombination, Genetic , Genome, Viral , Evolution, MolecularABSTRACT
Hydrogen sulfide (H2S), as an important small molecule bioregulator, plays a key role in many physiological activities and signaling, and abnormal fluctuations in H2S concentration can lead to a variety of diseases. Therefore, it is of great significance to develop a near-infrared fluorescence probe to visualize fluctuations in H2S levels. This work is based on Sulfur-substituted dicyanomethylene-4 H-chromene (DCM), A novel NIR fluorescent probe (E) -3 - (2 - (4 - (dicyanomethylene) -6-methyl-4 H-Thiochromen-2-yl)vinyl-1-methylquinolin-1-ium (DMT) was synthesized successfully. Research has found that in weakly alkaline environments, the probe DMT reacts rapidly with H2S (only 10 s), the fluorescence intensity at 684 nm is enhanced by about 60 fold, the detection limit is as low as 0.1623 µM, the Stokes shift is large (94 nm), and strong selectivity as well as anti-interference ability towards H2S. This will provide a new method for the rapid detection and further application of H2S.
ABSTRACT
BACKGROUND: Patients with DNA mismatch repair-proficient/microsatellite stable (pMMR/MSS) colorectal cancer (CRC), which accounts for 85% of all CRC cases, display a poor respond to immune checkpoint inhibitors (i.e., anti-PD-1 antibodies). pMMR/MSS CRC patients with locally advanced cancers need effective combined therapies. METHODS: In this pilot study, we administered six preoperative doses of each 2-week cycle of the anti-PD-1 antibody sintilimab (at a fixed dose of 200 mg), oxaliplatin, and 5-FU/CF (mFOLFOX6) combined with five doses of bevacizumab (the number of doses was reduced to prevent surgical delays) to patients with cT4NxM0 colon or upper rectal cancers. And radical surgery was performed approximately 2 weeks after the last dose of neoadjuvant therapy. The primary endpoint was a pathologic complete response (pCR). We also evaluated major pathologic response (MPR, ≤10% residual viable tumor), radiological and pathological regression, safety, and tumor mutation burden (TMB), and tumor microenvironment (TME) characteristics. RESULTS: By the cutoff date (September 2023), 22 patients with cT4NxM0 pMMR/MSS colon or upper rectal cancers were enrolled and the median follow-up was 24.7 months (IQR: 21.1-26.1). All patients underwent R0 surgical resection without treatment-related surgical delays. pCR occurred in 12 of 22 resected tumors (54.5%) and MPR occurred in 18 of 22 (81.8%) patients. At the cutoff date, all patients were alive, and 21/22 were recurrence-free. Treatment-related adverse events of grade 3 or higher occurred in of 2/22 (9.1%) patients. Among the pCR tumors, two were found to harbor POLE mutations. The degree of pathological regression was significantly greater than that of radiological regression (p = 1.35 × 10-8). The number of CD3+/CD4+ cells in the tumor and stroma in pretreated biopsied tissues was markedly lower in pCR tumors than in non-pCR tumors (p = 0.038 and p = 0.015, respectively). CONCLUSIONS: Neoadjuvant sintilimab combined with bevacizumab and mFOLFOX6 was associated with few side effects, did not delay surgery, and led to pCR and non-pCR in 54.5% and 81.8% of the cases, respectively. Downregulation of CD3/CD4 expression in the tumor and stroma is related to pCR. However, the molecular mechanisms underlying PD-1 blockade-enhanced targeted chemotherapy require further investigation.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Bevacizumab , Colorectal Neoplasms , Fluorouracil , Immune Checkpoint Inhibitors , Humans , Male , Female , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Aged , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Fluorouracil/therapeutic use , Fluorouracil/administration & dosage , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/adverse effects , Pilot Projects , Bevacizumab/therapeutic use , Bevacizumab/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Leucovorin/therapeutic use , Leucovorin/administration & dosage , DNA Mismatch Repair , Adult , Microsatellite Instability , Oxaliplatin/therapeutic use , Oxaliplatin/administration & dosage , Neoadjuvant Therapy/methods , Tumor Microenvironment/immunology , Organoplatinum Compounds/therapeutic use , Organoplatinum Compounds/administration & dosage , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Treatment OutcomeABSTRACT
BACKGROUND: Sika deer (Cervus nippon) holds significance among cervids, with three genomes recently published. However, these genomes still contain hundreds of gaps and display significant discrepancies in continuity and accuracy. This poses challenges to functional genomics research and the selection of an appropriate reference genome. Thus, obtaining a high-quality reference genome is imperative to delve into functional genomics effectively. FINDINGS: Here we report a high-quality consensus genome of male sika deer. All 34 chromosomes are assembled into single-contig pseudomolecules without any gaps, which is the most complete assembly. The genome size is 2.7G with 23,284 protein-coding genes. Comparative genomics analysis found that the genomes of sika deer and red deer are highly conserved, an approximately 2.4G collinear regions with up to 99% sequence similarity. Meanwhile, we observed the fusion of red deer's Chr23 and Chr4 during evolution, forming sika deer's Chr1. Additionally, we identified 607 transcription factors (TFs) that are involved in the regulation of antler development, including RUNX2, SOX6, SOX8, SOX9, PAX8, SIX2, SIX4, SIX6, SPI1, NFAC1, KLHL8, ZN710, JDP2, and TWST2, based on this consensus reference genome. CONCLUSIONS: Our results indicated that we acquired a high-quality consensus reference genome. That provided valuable resources for understanding functional genomics. In addition, discovered the genetic basis of sika-red hybrid fertility and identified 607 significant TFs that impact antler development.
Subject(s)
Antlers , Deer , Genome , Animals , Deer/genetics , Deer/growth & development , Antlers/growth & development , Antlers/metabolism , Male , Transcription Factors/genetics , Transcription Factors/metabolism , Gene Expression Profiling , Transcriptome , Genomics/methodsABSTRACT
An approach to achieve controllable non-uniformly distributed spiking cluster generation is proposed and demonstrated based on an externally-triggered broadband optoelectronic oscillator (OEO). The theory of controlling the distribution of the spiking pulses in a spiking cluster is established. Based on the theory, the dynamic and the distribution characteristics are analyzed and revealed in the stable spiking oscillation state under different externally-injected trigger signal voltages. The peak-voltage envelop of the cluster and the interval of the spiking pulses are demonstrated to have an approximate negative linearity relationship with the externally-injected trigger signal voltage in both the numerical simulation and the experiment, where a square waveform, a trapezoidal waveform, a parabola waveform, and a half-sinusoidal waveform are used as the externally-injected trigger signals. The results indicate that the spiking pulse distribution in the generated spiking cluster can be well controlled through tuning the externally-injected trigger signal voltage. The proposed scheme can be utilized in spiking encoding and reservoir computing.
ABSTRACT
An approach to generating stable phase-locked dual-frequency microwave signals is proposed and demonstrated based on a dual-passband optoelectronic oscillator (OEO). Mode gain competition is broken by employing frequency mixing mutual injection effect to realize phase locking between the two oscillation signals, which is achieved by applying a single-tone signal to a microwave mixer in the OEO cavity. In addition, a dual-loop configuration with balanced detection is utilized to ensure a high side mode suppression ratio (SMSR) and ultra-low phase noise, which also enhances the stability of the generated signal. In the experiment, a phase-locked dual-frequency microwave signal at 9.9982â GHz and 10.1155â GHz is generated by using the proposed OEO scheme. The SMSR and the phase noise are 75â dB and -141 dBc/Hz@10 kHz, respectively. Additionally, the Allan deviation of the generated signal is in the order of 10-11@1 s. These parameters are superior to those based on the same OEO but with a single-loop configuration, which are also compared in detail.
ABSTRACT
Ammonia (NH3) is an irritating and harmful gas that affects cell apoptosis and autophagy. Sirtuin 5 (SIRT5) has multiple enzymatic activities and regulates NH3-induced autophagy in tumor cells. In order to determine whether SIRT5 regulates NH3-induced bovine mammary epithelial cell apoptosis and autophagy, cells with SIRT5 overexpression or knockdown were generated and in addition, bovine mammary epithelial cells were treated with SIRT5 inhibitors. The results showed that SIRT5 overexpression reduced the content of NH3 and glutamate in cells by inhibiting glutaminase activity in glutamine metabolism, and reduced the ratio of ADP/ATP. The results in the SIRT5 knockdown and inhibitor groups were comparable, including increased content of NH3 and glutamate in cells by activating glutaminase activity, and an elevated ratio of ADP/ATP. It was further confirmed that SIRT5 inhibited the apoptosis and autophagy of bovine mammary epithelial cells through reverse transcription-quantitative PCR, western blot, flow cytometry with Annexin V FITC/PI staining and transmission electron microscopy. In addition, it was also found that the addition of LY294002 or Rapamycin inhibited the PI3K/Akt or mTOR kinase signal, decreasing the apoptosis and autophagy activities of bovine mammary epithelial cells induced by SIRT5-inhibited NH3. In summary, the PI3K/Akt/mTOR signal involved in NH3-induced cell autophagy and apoptosis relies on the regulation of SIRT5. This study provides a new theory for the use of NH3 to regulate bovine mammary epithelial cell apoptosis and autophagy, and provides guidance for improving the health and production performance of dairy cows.
ABSTRACT
A spindle-like Cu-based framework (Cu-Trp, Trp = L-Tryptophan) nanocrystal with ammonia-responsiveness was fabricated via simple aqueous solution approach, and it was subsequently explored as a functional compatibilizer of carboxymethyl starch/polyvinyl alcohol (CMS/PVA) blend toward constructing high-performance intelligent packaging films. The results showed that incorporation of Cu-Trp nanocrystal into CMS/PVA blend resulted in significant promotions regarding to the compatibility, mechanical strength (42.92 MPa), UV-blocking (with UV transmittance of only 2.4%), and water vapor barrier effectiveness of the blend film. Besides, the constructed CMS/PVA/Cu-Trp nanocomposite film exhibited superb long-term color stability, favorable antibacterial capacity (over 98.0%) toward both E. coli and S. aureus bacteria, as well as color change ability under ammonia environment. Importantly, the application trial confirmed that the CMS/PVA/Cu-Trp nanocomposite film is capable of visually monitoring shrimp spoilage during storage. These results implied that the CMS/PVA/Cu-Trp nanocomposite film holds tremendous potential as an intelligent active packaging material.
Subject(s)
Anti-Bacterial Agents , Copper , Escherichia coli , Food Packaging , Polyvinyl Alcohol , Staphylococcus aureus , Starch , Starch/chemistry , Starch/analogs & derivatives , Food Packaging/instrumentation , Polyvinyl Alcohol/chemistry , Escherichia coli/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Copper/chemistry , Nanoparticles/chemistry , Tryptophan/chemistry , Animals , Nanocomposites/chemistryABSTRACT
Considering public health and environmental safety, the development of reliable and efficient monitoring methods is essential to ensure food quality and safety. Herein, a new Cu-based metal organic framework (Cu-ICA) nanocrystal with ammonia-sensitive performance was built up and then introduced as a functional compatibilizer of starch/polyvinyl alcohol (STA/PVA) blend to develop high-performance intelligent packaging films for food freshness monitoring. The introduction of Cu-ICA upgraded the compatibility, mechanical strength (42.9 MPa), UV-protection (with UV transmittance of only 2.8 %), and moisture/oxygen barrier performances of STA/PVA film. Furthermore, the developed STA/PVA/Cu-ICA films presented long-term colour stability, outstanding antibacterial efficacy (over 99.5 %) toward both Escherichia coli and Staphylococcus aureus bacteria, as well as remarkable ammonia-sensitive discoloration capability. The STA/PVA/Cu-ICA films possessed visually identifiable colour change during the monitoring of shrimp spoilage. These findings indicate that the developed STA/PVA/Cu-ICA film possesses tremendous potential as an intelligent active packaging material.
Subject(s)
Anti-Bacterial Agents , Copper , Escherichia coli , Food Packaging , Polyvinyl Alcohol , Staphylococcus aureus , Starch , Food Packaging/methods , Polyvinyl Alcohol/chemistry , Starch/chemistry , Copper/chemistry , Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Nanoparticles/chemistry , Metal-Organic Frameworks/chemistry , Food Quality , Ammonia/chemistryABSTRACT
Background: Although malnutrition has been shown to influence the clinical outcomes of Stroke Patients with Bulbar Paralysis (SPBP), the prevalence and influencing factors have yet to be uncovered. Objective: This study aims to assess the current prevalence and factors associated with malnutrition in SPBP. Methods: A multicenter cross-sectional investigation was conducted among SPBP in China from 2019 to 2021. Information was collected on basic information, health condition, diagnosis, treatment, neurological function, activities of daily living, swallowing function, and nutritional status. A multivariable logistic regression model was used to identify the factors that influenced nutritional status. ROC analysis was used to assess the predictive value of each independent influencing factor and the logit model. Results: In total, 774 SPBP were enrolled, and the prevalence of malnutrition was 60.59%. Pulmonary infection [aOR:2.849, 95%CI: (1.426, 5.691)], hemoglobin [aOR: 0.932, 95%CI: (0.875, 0.982)], serum albumin [aOR: 0.904, 95%CI: (0.871, 0.938)], total protein [aOR: 0.891, 95%CI: (0.819, 0.969)], prealbumin [aOR: 0.962, 95%CI: (0.932, 0.993)], and National Institute of Health Stroke Scale (NIHSS) scores [aOR: 1.228, 95%CI: (1.054, 1.431)] were independent factors associated with malnutrition in SPBP. ROC analysis revealed that the logit model had the best predictive value [area under the curve: 0.874, 95% CI: (0.812, 0.936); specificity: 83.4%; sensitivity: 79.3%; p < 0.05]. Subgroup analysis showed that the nutritional status in dysphagic SPBP was additionally influenced by swallowing function and nutrition support mode. Conclusion: The prevalence of malnutrition in SPBP was 60.59%. Pulmonary infection, hemoglobin level, and NIHSS score were the independent factors associated with malnutrition. Swallowing function and nutrition support mode were the factors associated with malnutrition in dysphagic SPBP.
ABSTRACT
Malnutrition is a highly prevalent complication in patients with traumatic brain injury (TBI), and it is closely related to the prognosis of patients. Accurate identification of patients at high risk of malnutrition is essential. Therefore, we analyzed the risk factors of malnutrition in patients with TBI and developed a model to predict the risk of malnutrition. A retrospective collection of 345 patients with TBI, and they were divided into malnutrition and comparison groups according to the occurrence of malnutrition. Univariate correlation and multifactor logistic regression analyses were performed to determine patients' malnutrition risk factors. We used univariate and logistic regression (forward stepwise method) analyses to identify significant predictors associated with malnutrition in patients with TBI and developed a predictive model for malnutrition prediction. The model's discrimination, calibration, and clinical utility were evaluated using the receiver operating characteristic (ROC) curve, calibration plots, and decision curve analysis (DCA). A total of 216 patients (62.6%) developed malnutrition. Multifactorial logistic regression analysis showed that pulmonary infection, urinary tract infection, dysphagia, application of NGT, GCS score ≤ 8, and low ADL score were independent risk factors for malnutrition in patients with TBI (P < 0.05). The area under the curve of the model was 0.947. Calibration plots showed good discrimination of model calibration. DCA showed that the column line plot models were all clinically meaningful when nutritional interventions were performed over a considerable range of threshold probabilities (0-0.98). Malnutrition is widespread in patients with TBI, and the nomogram is a good predictor of whether patients develop malnutrition.
ABSTRACT
Ceramic coatings that can effectively prevent hydrogen permeation have a wide range of applications in hydrogen energy and nuclear fusion reactors. In this study, for the first time, the internal stress of Er2O3 coatings was found to be a key factor that could determine their hydrogen permeation resistance and lifespan. The internal stress was controlled by designing layered Er2O3 coatings. The internal stress increased with an increasing number of Er2O3 layers. When the number of layers was below 15, the increased internal stress did not adversely affect the coating performance and might help to increase its hydrogen permeation resistance. Although the overall thickness of the 15-layer Er2O3 coating was only 97 nm, its hydrogen permeation reduction factor (PRF) reached the highest value of 626, whereas a further increase in the internal stress detrimentally affected the ability of the coating to reduce hydrogen permeation. In addition, the experimental observations and simulation results revealed that the performance of the Er2O3 coatings was related to the hydrogen atoms that penetrated the coating, which weakened the Er-O bonds and consequently decreased the Er2O3 fracture limit. This study provides insights into the effects of internal stress and hydrogen penetration on the performance of ceramic coatings as hydrogen permeation barriers and will help guide strategies for the structure design of hydrogen permeation barriers possessing high PRFs and long lifespans.
ABSTRACT
Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2, which results in blindness in the working-age population, and there is currently no available treatment. Here, we report the results of the first-in-human clinical trial (NCT04722107) of gene therapy for Bietti crystalline corneoretinal dystrophy, including 12 participants who were followed up for 180-365 days. This open-label, single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein (rAAV2/8-hCYP4V2). Participants received a single unilateral subretinal injection of 7.5 × 1010 vector genomes of rAAV2/8-hCYP4V2. Overall, 73 treatment-emergent adverse events were reported, with the majority (98.6%) being of mild or moderate intensity and considered to be procedure- or corticosteroid-related; no treatment-related serious adverse events or local/systemic immune toxicities were observed. Compared with that measured at baseline, 77.8% of the treated eyes showed improvement in best-corrected visual acuity (BCVA) on day 180, with a mean ± standard deviation increase of 9.0 ± 10.8 letters in the 9 eyes analyzed (p = 0.021). By day 365, 80% of the treated eyes showed an increase in BCVA, with a mean increase of 11.0 ± 10.6 letters in the 5 eyes assessed (p = 0.125). Importantly, the patients' improvement observed using multifocal electroretinogram, microperimetry, and Visual Function Questionnaire-25 further supported the beneficial effects of the treatment. We conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2 (named ZVS101e).
Subject(s)
Corneal Dystrophies, Hereditary , Cytochrome P450 Family 4 , Dependovirus , Genetic Therapy , Retinal Diseases , Humans , Male , Female , Middle Aged , Adult , Corneal Dystrophies, Hereditary/genetics , Corneal Dystrophies, Hereditary/therapy , Corneal Dystrophies, Hereditary/pathology , Dependovirus/genetics , Cytochrome P450 Family 4/genetics , Genetic Vectors/genetics , Visual AcuityABSTRACT
Cerebral ischemia-reperfusion injury (CIRI) is one of the most difficult challenges in cerebrovascular disease research. It is primarily caused by excessive autophagy induced by oxidative stress. Previously, a novel compound X5 was found, and the excellent antioxidant activity of it was verified in this study. Moreover, network pharmacological analysis suggested that compound X5 was closely associated with autophagy and the mTOR pathway. In vitro, X5 could significantly inhibit the expression of autophagy proteins Beclin-1 and LC3-ß, which are induced by H2O2, and promote the expression of SIRT1. In vivo, compound X5 significantly reduced the infarct size and improved the neurological function scores in the middle cerebral artery occlusion (MCAO) model of rats. In conclusion, ROS-induced autophagy is closely related to mTOR, SIRT1 and others, and X5 holds promise as a candidate for the treatment of CIRI.
Subject(s)
Antioxidants , Autophagy , Network Pharmacology , Reperfusion Injury , Sirtuin 1 , TOR Serine-Threonine Kinases , Animals , Reperfusion Injury/drug therapy , Reperfusion Injury/metabolism , Autophagy/drug effects , Antioxidants/pharmacology , Rats , Sirtuin 1/metabolism , TOR Serine-Threonine Kinases/metabolism , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/pathology , Male , Brain Ischemia/drug therapy , Brain Ischemia/metabolism , Oxidative Stress/drug effects , Beclin-1/metabolism , Rats, Sprague-Dawley , Signal Transduction/drug effects , Disease Models, Animal , Hydrogen Peroxide/metabolismABSTRACT
BACKGROUND: Lung adenocarcinoma (LUAD), the most common and lethal subtype of lung cancer, continues to be a major health concern worldwide. Despite advances in targeted and immune therapies, only a minority of patients derive substantial benefits. As a result, the urgent need for novel therapeutic strategies to improve lung cancer treatment outcomes remains undiminished. METHODS: In our study, we employed the TIMER database to scrutinize TNFSF11 expression across various cancer types. We further examined the differential expression of TNFSF11 in normal and tumor tissues utilizing the TCGA-LUAD dataset and tissue microarray, and probed the associations between TNFSF11 expression and clinicopathological parameters within the TCGA-LUAD dataset. We used the GSE31210 dataset for external validation. To identify genes strongly linked to TNFSF11, we engaged LinkedOmics and conducted a KEGG pathway enrichment analysis using the WEB-based Gene SeT AnaLysis Toolkit. Moreover, we investigated the function of TNFSF11 through gene knockdown or overexpression approaches and explore its function in tumor cells. The therapeutic impact of ferroptosis inducers in tumors overexpressing TNFSF11 were also investigated through in vivo and in vitro experiments. Through these extensive analyses, we shed light on the potential role of TNFSF11 in lung adenocarcinoma, underscoring potential therapeutic targets for this malignancy. RESULTS: This research uncovers the overexpression of TNFSF11 in LUAD patients and its inverse correlation with peroxisome-related enzymes. By utilizing gene knockdown or overexpression assays, we found that TNFSF11 was negatively associated with GPX4. Furthermore, cells with TNFSF11 overexpression were relatively more sensitive to the ferroptosis inducers. CONCLUSIONS: Our research has provided valuable insights into the role of TNFSF11, revealing its negative regulation of GPX4, which could be influential in crafting therapeutic strategies. These findings set the stage for further exploration into the mechanisms underpinning the relationship between TNFSF11 and GPX4, potentially opening up new avenues for precision medicine in the treatment of LUAD.
Subject(s)
Adenocarcinoma of Lung , Ferroptosis , Lung Neoplasms , Humans , Adenocarcinoma of Lung/genetics , Biological Assay , Databases, Factual , Ferroptosis/genetics , Lung Neoplasms/genetics , RANK LigandABSTRACT
Fusarium head blight (FHB) and the presence of mycotoxin deoxynivalenol (DON) pose serious threats to wheat production and food safety worldwide. DON, as a virulence factor, is crucial for the spread of FHB pathogens on plants. However, germplasm resources that are naturally resistant to DON and DON-producing FHB pathogens are inadequate in plants. Here, detoxifying bacteria genes responsible for DON epimerization were used to enhance the resistance of wheat to mycotoxin DON and FHB pathogens. We characterized the complete pathway and molecular basis leading to the thorough detoxification of DON via epimerization through two sequential reactions in the detoxifying bacterium Devosia sp. D6-9. Epimerization efficiently eliminates the phytotoxicity of DON and neutralizes the effects of DON as a virulence factor. Notably, co-expressing of the genes encoding quinoprotein dehydrogenase (QDDH) for DON oxidation in the first reaction step, and aldo-keto reductase AKR13B2 for 3-keto-DON reduction in the second reaction step significantly reduced the accumulation of DON as virulence factor in wheat after the infection of pathogenic Fusarium, and accordingly conferred increased disease resistance to FHB by restricting the spread of pathogenic Fusarium in the transgenic plants. Stable and improved resistance was observed in greenhouse and field conditions over multiple generations. This successful approach presents a promising avenue for enhancing FHB resistance in crops and reducing mycotoxin contents in grains through detoxification of the virulence factor DON by exogenous resistance genes from microbes.
Subject(s)
Disease Resistance , Fusarium , Plant Diseases , Trichothecenes , Triticum , Triticum/microbiology , Triticum/genetics , Triticum/metabolism , Fusarium/pathogenicity , Trichothecenes/metabolism , Plant Diseases/microbiology , Plant Diseases/genetics , Plant Diseases/immunology , Disease Resistance/genetics , Genes, Bacterial/geneticsABSTRACT
We present an efficient tunable all-silica-fiber 2nd-order cascaded Raman pulse laser utilizing 2-µm dissipative-soliton-resonance (DSR) rectangular pulses for pumping and highly GeO2-doped silica fiber as Raman gain medium. When pumped at 1966.5â nm, the maximum 1st-order Raman optical conversion efficiency is up to 64.4% at 2153â nm, with 92.4% spectral purity and 0.39-W average power. The maximum 2nd-order Raman optical conversion efficiency is 19.3% at 2370â nm, with 39.2% spectral purity and 0.25-W average power. To our knowledge, these conversion efficiencies and spectral purities represent the highest levels achieved in a mid-infrared all-silica-fiber cascaded pulsed Raman laser. Additionally, by adjusting the central wavelength of the DSR seed pulse, the 2nd-order Raman light can be tuned within a range of 41â nm (2354â¼2395â nm). Our system provides a simple and easy-to-implement solution for realizing efficient tunable cascaded pulsed Raman lasers in the 2.4-µm band.
ABSTRACT
BACKGROUND: Nasogastric tube feeding (NG) has been widely used in patients with bulbar palsy after ischemic stroke but is associated with a significant risk of complications including malnutrition and pneumonia. Intermittent oro-esophageal tube feeding (IOE) can help alleviate these concerns. This study explored the clinical effect of IOE versus NG on nutritional status, swallowing function, stroke-associated pneumonia, and depression in patients with bulbar palsy after ischemic stroke. METHODS: This randomized controlled study included 148 patients with bulbar palsy after ischemic stroke who underwent routine treatment and swallowing rehabilitation training in the Department of Rehabilitation Medicine between July 2017 and July 2019 in China. The participants were randomly divided into the IOE group (n=74) and NG group (n=74) with IOE and NG as nutritional supports, respectively. The primary outcome was nutritional status including (1) body mass index (kg/m2), (2) serum ALB (albumin, g/L), and (3) PA (prealbumin, mg/L). The secondary outcomes were (1) swallowing function including (i) Functional Oral Intake Scale (FOIS) and (ii) Penetration-Aspiration Scale, (2) pneumonia, (3) depression, and (4) adverse events. Statistical analyses for continuous outcomes were performed using t test, Mann-Whitney U test and Wilcoxon signed-rank test and categorical variables using χ2 test. SPSS 21.0 was used for all analysis. RESULTS: There were no significant baseline differences between the 2 groups. After the treatment, the IOE group demonstrated significantly better results compared with the NG group in ALB ([32.71±0.94] versus [32.28±0.81] g/L; P=0.003), PA ([278.15±13.81] versus [270.31±15.08] mg/L; P=0.001], body mass index ([19.77±1.03] versus [19.41±0.98] kg/m2; P=0.002], FOIS (P<0.001), Penetration-Aspiration Scale (P<0.001), stroke-associated pneumonia ([1, 4.05%] versus [26, 35.14%]; P<0.001), depression ([1, 1.35%] versus [44, 59.46%]; P<0.001) and overall less adverse events (reflux, fever, discomfort in the throat; P<0.001). CONCLUSIONS: In patients with dysphagia with bulbar palsy after ischemic stroke who received routine treatment and swallowing rehabilitation training, IOE is safer and more conducive to the improvement of nutritional status, swallowing function, stroke-associated pneumonia, and depression than NG. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR-INC-17011741.
ABSTRACT
Bisulfite (HSO3-) and biological thiols molecules, such as glutathione (GSH), cysteine (Cys), and homocysteine (Hcy), play important roles in organisms. Developing a fluorescent probe that can simultaneously detect and distinguish HSO3- and biological thiols is of great significance. In this study, ethyl(2E,4Z)-5-chloro-2-cyano-5-(7-(diethylamino)-2-oxo-2 H-chromen-3-yl)penta-2,4-dienoate (CCO) as a novel enhanced fluorescence probe was synthesized by integrating coumarin derivatives and ethyl cyanoacetate, which can simultaneous detection and discrimination of hydrogen bisulfite anions and glutathione. The sensing mechanism was elucidated through spectral analysis and some control experiments. In weakly alkaline environments, the probe not only has good selectivity for HSO3- and GSH, but also has a lower detection limits of 0.0179 µM and 0.2034 µM. The probe exhibited fuorescent turn-on for distinguishing with 296 and 28 fold the fluorescent intensity increase at 486 and 505 nm, respectively, through diferent excitation wavelengths. This provides a new method for simultaneous detection and discrimination of HSO3- and biological thiol cell levels and further applications.