Vocal communication plays an important role in survival, reproduction, and animal social association. Birds and mammals produce complex vocal sequence to convey context-dependent information. Vocalizations are conspicuous features of the behavior of most anuran species (frogs and toads), and males usually alter their calling strategies according to ecological context to improve the attractiveness/competitiveness. However, very few studies have focused on the variation of vocal sequence in anurans. In the present study, we used both conventional method and network analysis to investigate the context-dependent vocal repertoire, vocal sequence, and call network structure in serrate-legged small treefrogs Kurixalus odontotarsus. We found that male K. odontotarsus modified their vocal sequence by switching to different call types and increasing repertoire size in the presence of a competitive rival. Specifically, compared with before and after the playback of advertisement calls, males emitted fewer advertisement calls, but more aggressive calls, encounter calls, and compound calls during the playback period. Network analysis revealed that the mean degree, mean closeness, and mean betweenness of the call networks significantly decreased during the playback period, which resulted in lower connectivity. In addition, the increased proportion of one-way motifs and average path length also indicated that the connectivity of the call network decreased in competitive context. However, the vocal sequence of K. odontotarsus did not display a clear small-world network structure, regardless of context. Our study presents a paradigm to apply network analysis to vocal sequence in anurans and has important implications for understanding the evolution and function of sequence patterns.
The removal of crude oil from spent hydrodesulfurization catalysts constitutes the preliminary stage in the recovery process of valuable metals. However, the traditional roasting method for the removal exhibits massive limitations. In view of this, the present study used an ultrasound-assisted surfactant cleaning method to remove crude oil from spent hydrodesulfurization catalysts, which demonstrated effectiveness. Furthermore, the study investigated the mechanism governing the process with calculation and experiments, so as to provide a comprehensive understanding of the cleaning method's efficacy. The surfactant selection was predicated on the performance in the IFT test, with SDBS and TX-100 finally being chosen. Subsequent calculations and analysis were then conducted to elucidate their frontier molecular orbitals, electrostatic potential, and polarity. It has been found that both SDBS and TX-100 possess the smallest LUMO-HOMO energy gap (ΔE), registering at 4.91 eV and 4.80 eV, respectively, and presenting the highest interfacial reactivity. The hydrophilic structure in the surfactant regulates the wettability of the oil-water interface, and the long-chain alkanes have excellent non-polar properties that promote the dissolution of crude oil. The ultrasonic-assisted process further improves the interface properties and enhances the oil removal effect. Surprisingly, the crude oil residue was reduced to 0.25% under optimal conditions. The final phase entailed the techno-economic evaluation of the entire process, revealing that, in comparison to the roasting method, this process saves $0.38 per kilogram of spent HDS catalyst, with the advantages of operational simplicity and emission-free. Generally, this study shed new light on the realization of efficient oil removal, with the salience of green, sustainable, and economical.
Pyruvate kinase isoform 2 (PKM2) is closely related to the regulation of Th17/Treg balance, which is considered to be an effective strategy for UC therapy. Parthenolide (PTL), a natural product, only possesses moderate PKM2-activating activity. Thus, five series of PTL derivatives are designed and synthesized to improve PKM2-activated activities and anti-UC abilities. Through detailed structure optimization, B4 demonstrates potent T-cell anti-proliferation activity (IC50 = 0.43 µM) and excellent PKM2-activated ability (AC50 = 0.144 µM). Subsequently, through mass spectrometry analysis, B4 is identified to interact with Cys423 of PKM2 via covalent-bond. Molecular docking and molecular dynamic simulation results reveal that the trifluoromethoxy of B4 forms a stronger hydrophobic interaction with Ala401, Pro402, and Ile403. In addition, B4 has a significant effect only on Th17 cell differentiation, thereby regulating the Th17/Treg balance. The effect of B4 on Th17/Treg imbalance can be attributed to inhibition of PKM2 dimer translocation and suppression of glucose metabolism. Finally, B4 can notably ameliorate the symptoms of dextran sulfate sodium (DSS)-induced colitis in mouse model in vivo. Thus, B4 is confirmed as a potent PKM2 activator, and has the potential to develop as a novel anti-UC agent.
Numerous studies have shown that oxidative stress plays an important role in peripheral artery disease (PAD). Prior reports suggested autonomic dysfunction in PAD. We hypothesized that responses of the autonomic nervous system and coronary tone would be impaired in patients with PAD during exposure to acute hyperoxia, an oxidative stressor. In 20 PAD patients and 16 healthy, sex and age-matched controls, beat-by-beat heart rate (HR, from ECG) and blood pressure (BP, with Finometer) were recorded for 10 minutes during room air breathing and 5 minutes of hyperoxia. Cardiovagal baroreflex sensitivity and HR variability (HRV) were evaluated as measures of autonomic function. Transthoracic coronary echocardiography was used to assess peak coronary blood flow velocity (CBV) in the left anterior descending coronary artery. Cardiaovagal baroreflex sensitivity at rest was lower in PAD than in healthy controls. Hyperoxia raised BP solely in the patients with PAD, with no change observed in healthy controls. Hyperoxia induced an increase in cardiac parasympathetic activity assessed by the high-frequency component of HRV in healthy controls but not in PAD. Indices of parasympathetic activity were lower in PAD than in healthy controls throughout the trial as well as during hyperoxia. Hyperoxia induced coronary vasoconstriction in both groups, while the coronary perfusion time fraction was lower in PAD than in healthy controls. These results suggest that the response in parasympathetic activity to hyperoxia (i.e., oxidative stress) is blunted and the coronary perfusion time is shorter in PAD patients.
Recently, aiming for the enhanced dispersibility of graphene-based nanomaterials in lubricating oil matrices to serve as highly efficient lubricant additives, numerous modification approaches have been extensively studied. However, these previous modification routes usually involve a tedious multistep modification process or multitudinous toxic reagents, restricting their extensive practical application. In this work, novel graphene oxide (GO) nanoadditives (RGO-g-BO) featuring excellent durable dispersion capability and remarkable tribological performance were successfully prepared via an environmentally friendly one-step approach consisting of surface grafting of long-chain bromooctadecane (BO) and in situ chemical reduction. Benefiting from the greatly improved lipophilicity (resulting from the introduction of hydrophobic long-chain alkane groups and chemical reduction), along with the miniaturization effect, RGO-g-BO exhibits superior long-term dispersion stability in the finished oil. Moreover, the tribological properties results demonstrated that the finished oil filled with RGO-g-BO nanolubricants achieved an outstanding friction-reducing and antiwear performance. Particularly, under the optimum content of RGO-g-BO (as low as 0.005 wt%), the friction coefficient as well as the wear volume of the composite finished oil were greatly reduced by 13% and 53%, respectively, as compared with nascent finished oil. Therefore, in view of the advantages of low-cost, one-step facile synthesis, desirable dispersion capability, and remarkable tribological performance, RGO-g-BO holds great prospects as a highly efficient lubrication additive in the tribology field.
The global dairy market has been increasingly diversified with more dairy product offerings of milk products from different animal species. Meanwhile, milk powders remain the main exported dairy product format due to their ease of transportation. In this work, we studied the structural changes, protein hydrolysis and nutrient delivery during dynamic gastric digestion and small intestinal digestion of cow, goat and sheep milk reconstituted from commercial whole milk powders. The results show that the reconstituted milks digest similarly to processed fresh milk. The digestion behaviors of the three reconstituted ruminant milks are broadly similar (gastric coagulation, kinetics of gastric emptying of protein and fat and the high digestibility in the small intestine) with some differences, which are likely contributed by the processing history of the milk powders. The delivery of individual amino acids to the small intestine differed between the early and late stages of gastric digestion, which were primarily affected by the abundance of amino acids in caseins and whey proteins but also by the difference between milk types associated with their gastric coagulation behaviors. This work showed that powdered milk is similar to fresh processed milk in digestion behavior, and the inherent differences between ruminant milks can be modified by processing treatments.
BACKGROUND: Atherosclerosis, a leading cause of cardiovascular disease, involves the pathological activation of various cell types, including immunocytes (eg, macrophages and T cells), smooth muscle cells (SMCs), and endothelial cells. Accumulating evidence suggests that transition of SMCs to other cell types, known as phenotypic switching, plays a central role in atherosclerosis development and complications. However, the characteristics of SMC-derived cells and the underlying mechanisms of SMC transition in disease pathogenesis remain poorly understood. Our objective is to characterize tumor cell-like behaviors of SMC-derived cells in atherosclerosis, with the ultimate goal of developing interventions targeting SMC transition for the prevention and treatment of atherosclerosis. METHODS: We used SMC lineage tracing mice and human tissues and applied a range of methods, including molecular, cellular, histological, computational, human genetics, and pharmacological approaches, to investigate the features of SMC-derived cells in atherosclerosis. RESULTS: SMC-derived cells in mouse and human atherosclerosis exhibit multiple tumor cell-like characteristics, including genomic instability, evasion of senescence, hyperproliferation, resistance to cell death, invasiveness, and activation of comprehensive cancer-associated gene regulatory networks. Specific expression of the oncogenic mutant KrasG12D in SMCs accelerates phenotypic switching and exacerbates atherosclerosis. Furthermore, we provide proof of concept that niraparib, an anticancer drug targeting DNA damage repair, attenuates atherosclerosis progression and induces regression of lesions in advanced disease in mouse models. CONCLUSIONS: Our findings demonstrate that atherosclerosis is an SMC-driven tumor-like disease, advancing our understanding of its pathogenesis and opening prospects for innovative precision molecular strategies aimed at preventing and treating atherosclerotic cardiovascular disease.
Pain is a widespread motivation for seeking healthcare and stands as a substantial global public health concern. Despite comprehensive investigations into the mechanisms of pain sensitization induced by inflammation, efficacious treatments options remain scarce. Neutrophil extracellular traps (NETs) have been associated with the progression and tissue damage of diverse inflammatory diseases. This study aims to explore the impact of NETs on the progression of inflammatory pain and explore potential therapeutic approaches. Initially, we observed neutrophil infiltration and the formation of NETs in the left hind paw of mice with inflammatory pain induced by complete Freund's adjuvant (CFA). Furthermore, we employed the peptidyl arginine deiminase 4 (PAD4) inhibitor Cl-amidine (diluted at 50 mg/kg in saline, administered via tail vein injection once daily for three days) to impede NETs formation and administered DNase1 (diluted at 10 mg/kg in saline, once daily for three days) to break down NETs. We investigated the pathological importance of peripheral NETs formation in inflammatory pain and its influence on the activation of spinal dorsal horn microglia. The findings indicate that neutrophils infiltrating locally generate NETs, leading to an increased release of inflammatory mediators that worsen peripheral inflammatory reactions. Consequently, this results in the transmission of more harmful peripheral stimuli to the spinal cord, triggering microglial activation and NF-κB phosphorylation, thereby escalating neuroinflammation and fostering pain sensitization. Suppression of peripheral NETs can mitigate peripheral inflammation in mice with inflammatory pain, reverse mechanical and thermal hypersensitivity by suppressing microglial activation in the spinal cord, ultimately diminishing inflammatory pain. In conclusion, these discoveries propose that obstructing or intervening with NETs introduces a novel therapeutic avenue for addressing inflammatory pain.
Extracellular Traps , Mice , Animals , Pain/drug therapy , Inflammation/pathology , Neutrophils/pathology , Spinal Cord Dorsal Horn
DOM is the largest reservoir of organic carbon in the world, and it plays a crucial role in the biogeochemical cycles of natural water bodies. A river is a transition area connecting source water and receiving water that controls the DOM exchange between them. Therefore, in this study, ultraviolet visible spectroscopy (UV-vis) and three-dimensional fluorescence spectroscopy (EEMs) combined with parallel factor analysis (PARAFAC) were used to analyze the spectral characteristics and sources of dissolved organic matter in the Fuhe River, Xiaobai River, Baigouyin River, and Puhe River of Baiyangdian. The results showed that a245 and a355 in the Fuhe River and Xiaobai River were significantly higher than those in the Baigouyin River and Puhe River. E2/E3 showed that the DOM relative molecular mass of the inflow river water body was Puhe River > Baigouyin River > Fuhe River > Xiaobai River. Three components, tyrosine-like (C1), terrigenous humus (C2), and tryptophan-like (C3), were determined using three-dimensional fluorescence through PARAFAC. There was no difference among the fluorescence components (P>0.05), but there were differences among the C2 and C3 components (P<0.05). The proportion of easily degradable protein-like components (C1+C3) was higher than that of humus-like components (C2). The autogeny index BIX was greater than 1, and the humification index HIX was less than 4, indicating that the autogeny characteristics of the river bodies were obvious, and the humification degree was weak. The FI index was the highest (1.96±0.25), and the HIX index was the lowest (0.46±0.08), and the self-generated source characteristics gradually strengthened along the direction of the river entering the lake, indicating that the water body of the Fuhe River showed higher endogenous and autogenic characteristics. Based on the correlation analysis of fluorescence components and characteristic parameters of DOM, the correlations between the Fuhe River and Xiaobaihe River and between the Baigouyin River and Puhe River bodies were similar. The correlation between fluorescence components of DOM and water quality parameters of each lake was significantly different, and it was strongly correlated with nitrogen and phosphorus in water. According to multiple linear regression analysis, there was no significant difference among C1 components, but there was a significant difference between C2 and C3 components. In summary, the carbon cycle process of Baiyangdian Lake was further understood through the study on the DOM spectral characteristics and sources of the inflow river waters in the summer flood season.
Growing evidence suggests that gain or amplification [gain/amp(1q)] accumulates during disease progression of multiple myeloma (MM). Previous investigations have indicated that small gain/amp(1q) subclones present at the time of diagnosis may evolve into dominant clones upon MM relapse. However, the influence of a minor clone of gain/amp(1q) on MM survival, as well as the correlation between different clonal sizes of gain/amp(1q) and the chromosomal instability (CIN) of MM, remains poorly understood. In this study, we analyzed fluorescence in situ hybridization (FISH) results of 998 newly diagnosed MM (NDMM) patients. 513 patients were detected with gain/amp(1q) at diagnosis. Among these 513 patients, 55 had a minor clone (≤20%) of gain/amp(1q). Patients with a minor clone of gain/amp(1q) displayed similar survival outcomes compared to those without gain/amp(1q). Further analysis demonstrated patients with a minor clone of gain/amp(1q) exhibited a clonal architecture similar to those without gain/amp(1q). Lastly, our results showed a significant increase in the clonal size of the minor clone of gain/amp(1q), frequently observed in MM. These findings suggested that a minor clone of gain/amp(1q) might represent an earlier stage in the pathogenesis of gain/amp(1q) and propose a "two-step" process in the clonal size changes of gain/amp(1q) in MM.
BACKGROUND: Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is a heterogeneous state of chronic intestinal inflammation. Intestinal innate immunity, including innate immune cells, defends against pathogens and excessive entry of gut microbiota, while preserving immune tolerance to resident intestinal microbiota, and may be characterized by its capacity to produce a rapid and nonspecific reaction. The association between microbiota dysbiosis and the pathogenesis of IBD is complex and dynamic. When the intestinal ecosystem is in dysbiosis, the reduced abundance and diversity of intestinal gut microbiota make the host more vulnerable to the attack of exogenous and endogenous pathogenic gut microbiota. The aim of our study was to comprehensively assess the relationship between microbial populations within UC, the signaling pathways of pathogenic gut microbe therein and the inflammatory response, as well as to understand the effects of using PE&AFWE (poppy extract [Papaver nudicaule L.] and Artemisia frigida Willd. extract) on UC modulation. METHODS: A UC mouse model was established by inducing SPF-grade C57BL/6 mice using dextrose sodium sulfate (DSS). Based on metagenomic sequencing to characterize the gut microbiome, the relationship between gut microbiota dysbiosis and gut microbiota was further studied using random forest and Bayesian network analysis methods, as well as histopathological analysis. RESULTS: (1) We found that the 5 gut microbiota with the highest relative abundance of inflammatory bowel disease UC model gut microbiota were consistent with the top 5 ranked natural bacteria. There were three types of abundance changes in the model groups: increases (Chlamydiae/Proteobacteria and Deferribacteres), decreases (Firmicutes), and no significant changes (Bacteroidetes). The UC model group was significantly different from the control group, with 1308 differentially expressed species with abundance changes greater than or equal to 2-fold. (2) The proportion of the fecal flora in the UC group decreased by 37.5% in the Firmicutes and increased by 14.29% in the proportion of Proteobacteria compared to the control group before treatment. (3) The significantly enriched and increased signaling pathways screened were the 'arachidonic acid metabolic pathway' and the 'phagosomal pathway', which both showed a decreasing trend after drug administration. (4) Based on the causal relationship between different OTUs and the UC model/PE&AFWE administration, screening for directly relevant OTU networks, the UC group was found to directly affect OTU69, followed by a cascade of effects on OTU12, OTU121, OTU93, and OTU7, which may be the pathway of action that initiated the pathological changes in normal mice. (5) We identified a causal relationship between common differentially expressed OTUs and PE&AFWE and UC in the pre- and post-PE&AFWE-treated groups. Thereby, we learned that PE&AFWE can directly affect OTU90, after which it inhibits UC, inhibiting the activity of arachidonic acid metabolic pathway by affecting OTU118, which in turn inhibits the colonization of gut microbiota by OTU93 and OTU7. (6) Histopathological observation and scoring (HS) of the colon showed that there was a significant difference between the model group and the control group (p < 0.001), and that there was a significant recovery in both the sulfasalazine (SASP)and the PE&AFWE groups after the administration of the drug (p < 0.0001). CONCLUSION: We demonstrated causal effects and inflammatory metabolic pathways in gut microbiota dysbiosis and IBD, with five opportunistic pathogens directly contributing to IBD. PE&AFWE reduced the abundance of proteobacteria in the gut microbiota, and histopathology showed significant improvement.
Colitis, Ulcerative , Dextran Sulfate , Disease Models, Animal , Gastrointestinal Microbiome , Mice, Inbred C57BL , Animals , Gastrointestinal Microbiome/drug effects , Colitis, Ulcerative/microbiology , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/pathology , Dextran Sulfate/pharmacology , Mice , Dysbiosis , Male , Inflammation
Malignant melanoma (MM) is a highly aggressive and deadly form of skin cancer, primarily caused by recurrence and metastasis. Therefore, it is crucial to investigate the regulatory mechanisms underlying melanoma recurrence and metastasis. Our study has identified a potential targeted regulatory relationship between LINC02202, miR-526b-3p and XBP1 in malignant melanoma. Through the regulation of the miR-526b-3p/XBP1 signalling pathway, LINC02202 may play a role in tumour progression and immune infiltration and inhibiting the expression of LINC02202 can increase the efficacy of immunotherapy for melanoma. Our findings shed light on the impact of LINC02202/XBP1 on the phenotype and function of malignant melanoma cells. Furthermore, this study provides a theoretical foundation for the development of novel immunotherapy strategies for malignant melanoma.
Melanoma , MicroRNAs , Skin Neoplasms , Humans , Melanoma/drug therapy , Melanoma/genetics , Melanoma/pathology , MicroRNAs/metabolism , Programmed Cell Death 1 Receptor/metabolism , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Cell Line, Tumor , Skin Neoplasms/genetics , Drug Delivery Systems , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , X-Box Binding Protein 1/genetics , X-Box Binding Protein 1/metabolism
Objective. The development of electrical pulse stimulations in brain, including deep brain stimulation, is promising for treating various brain diseases. However, the mechanisms of brain stimulations are not yet fully understood. Previous studies have shown that the commonly used high-frequency stimulation (HFS) can increase the firing of neurons and modulate the pattern of neuronal firing. Because the generation of neuronal firing in brain is a nonlinear process, investigating the characteristics of nonlinear dynamics induced by HFS could be helpful to reveal more mechanisms of brain stimulations. The aim of present study is to investigate the fractal properties in the neuronal firing generated by HFS.Approach. HFS pulse sequences with a constant frequency 100 Hz were applied in the afferent fiber tracts of rat hippocampal CA1 region. Unit spikes of both the pyramidal cells and the interneurons in the downstream area of stimulations were recorded. Two fractal indexes-the Fano factor and Hurst exponent were calculated to evaluate the changes of long-range temporal correlations (LRTCs), a typical characteristic of fractal process, in spike sequences of neuronal firing.Mainresults. Neuronal firing at both baseline and during HFS exhibited LRTCs over multiple time scales. In addition, the LRTCs significantly increased during HFS, which was confirmed by simulation data of both randomly shuffled sequences and surrogate sequences.Conclusion. The purely periodic stimulation of HFS pulses, a non-fractal process without LRTCs, can increase rather than decrease the LRTCs in neuronal firing.Significance. The finding provides new nonlinear mechanisms of brain stimulation and suggests that LRTCs could be a new biomarker to evaluate the nonlinear effects of HFS.
Hippocampus , Neurons , Rats , Animals , Rats, Sprague-Dawley , Neurons/physiology , Hippocampus/physiology , Axons/physiology , CA1 Region, Hippocampal/physiology , Electric Stimulation/methods
We report on the light pulse storage in Pr3+:Y2SiO5 crystal based on the revival of silenced echo protocol, which has the advantage of being immune from the spontaneous emission noise. We optimized the echo retrieval efficiency of the light pulse by employing complex hyperbolic secant rephasing pulses and by finely tuning the optical depth in the inhomogeneous broadening of the crystal. An echo retrieval efficiency of 24.4% was demonstrated, and an optical coherence time of 34.6 µs was extracted from the measured decay dynamics of the echo retrieval efficiency at a cryogenic temperature of 3.4 K. These results could be useful for potential applications in quantum memory and related applications.
Cardiovascular disease is a main cause of mortality in the world and the highest incidence of all diseases. However, the mechanism of the pathogenesis of cardiovascular disease is still unclear, and we need to continue to explore its mechanism of action. The occurrence and development of cardiovascular disease is significantly associated with genetic abnormalities, and gene expression is affected by transcriptional regulation. In this complex process, the protein-protein interaction promotes the RNA polymerase II to the initiation site. And in this process of transcriptional regulation, transcriptional cofactors are responsible for passing cues from enhancers to promoters and promoting the binding of RNA polymerases to promoters, so transcription cofactors playing a key role in gene expression regulation. There is growing evidence that transcriptional cofactors play a critical role in cardiovascular disease. Transcriptional cofactors can promote or inhibit transcription by affecting the function of transcription factors. It can affect the initiation and elongation process of transcription by forming complexes with transcription factors, which are important for the stabilization of DNA rings. It can also act as a protein that interacts with other proteins to affect the expression of other genes. Therefore, the aim of this overview is to summarize the effect of some transcriptional cofactors such as BRD4, EP300, MED1, EZH2, YAP, SIRT6 in cardiovascular disease and to provide a promising therapeutic strategy for the treatment of cardiovascular disease.
Cardiovascular Diseases , Sirtuins , Humans , Transcription Factors/genetics , Transcription Factors/metabolism , Transcription, Genetic , Nuclear Proteins/metabolism , Cardiovascular Diseases/genetics , Gene Expression Regulation , RNA Polymerase II/metabolism , Bromodomain Containing Proteins , Cell Cycle Proteins/metabolism , Sirtuins/metabolism
BACKGROUND: This study presents a case of rapidly developing respiratory failure due to antisynthetase syndrome (AS) following coronavirus disease 2019 (COVID-19) in a 33-year-old man diagnosed with Klinefelter syndrome (KS). CASE SUMMARY: A 33-year-old man with a diagnosis of KS was admitted to the Department of Pulmonary and Critical Care Medicine of a tertiary hospital in China for fever and shortness of breath 2 wk after the onset of COVID-19. Computed tomography of both lungs revealed diffuse multiple patchy heightened shadows in both lungs, accompanied by signs of partial bronchial inflation. Metagenomic next-generation sequencing of the bronchoalveolar lavage fluid suggested absence of pathogen. A biopsy specimen revealed organizing pneumonia with alveolar septal thickening. Additionally, extensive auto-antibody tests showed strong positivity for anti-SSA, anti-SSB, anti-Jo-1, and anti-Ro-52. Following multidisciplinary discussions, the patient received a final diagnosis of AS, leading to rapidly progressing respiratory failure. CONCLUSION: This study underscores the clinical progression of AS-associated interstitial lung disease subsequent to viral infections such as COVID-19 in patients diagnosed with KS.
Developing an effective and efficient electroencephalography (EEG)-based drowsiness monitoring system is crucial for enhancing road safety and reducing the risk of accidents. For general usage, cross-subject evaluation is indispensable. Despite progress in unsupervised domain adaptation (UDA) and source-free domain adaptation (SFDA) methods, these often rely on the availability of labeled source data or white-box source models, posing potential privacy risks. This study explores a more challenging setting of UDA for EEG-based drowsiness detection, termed black-box domain adaptation (BBDA). In BBDA, adaptation in the target domain relies solely on a black-box source model, without access to the source data or parameters of the source model. To address these privacy concerns, we propose a framework called Self-distillation and Pseudo-labelling for Ensemble Deep Random Vector Functional Link (edRVFL)-based Black-box Knowledge Adaptation (SPARK). SPARK employs entropy-based selection of high-confidence samples, which are then pseudo-labeled to train a student edRVFL network. Subsequently, ensemble self-distillation is performed to extract knowledge by training the edRVFL using refined labels introduced by ensemble learning. This process further improves the robustness of the student edRVFL network. The use of edRVFL as the student network offers advantages such as a closed-form solution, fast computation, and ease of implementation. These features are beneficial for improving the computational efficiency of the framework, making it more suitable for tasks involving small datasets. The proposed SPARK framework is evaluated on two publicly available driver drowsiness datasets. Experimental results demonstrate its superior performance over strong baselines, while significantly reducing training time. These findings underscore the potential for practical integration of the proposed framework into drowsiness monitoring systems, thereby contributing substantially to the privacy preservation of source subjects.
BACKGROUND: Low-dose ionizing radiation-induced protection and damage are of great significance among radiation workers. We aimed to study the role of glutathione S-transferase Pi (GSTP1) in low-dose ionizing radiation damage and clarify the impact of ionizing radiation on the biological activities of cells. RESULTS: In this study, we collected peripheral blood samples from healthy adults and workers engaged in radiation and radiotherapy and detected the expression of GSTP1 by qPCR. We utilized γ-rays emitted from uranium tailings as a radiation source, with a dose rate of 14 µGy/h. GM12878 cells subjected to this radiation for 7, 14, 21, and 28 days received total doses of 2.4, 4.7, 7.1, and 9.4â¯mGy, respectively. Subsequent analyses, including flow cytometry, MTS, and other assays, were performed to assess the ionizing radiation's effects on cellular biological functions. In peripheral blood samples collected from healthy adults and radiologic technologist working in a hospital, we observed a decreased expression of GSTP1 mRNA in radiation personnel compared to the healthy controls. In cultured GM12878 cells exposed to low-dose ionizing radiation from uranium tailings, we noted significant changes in cell morphology, suppression of proliferation, delay in cell cycle progression, and increased apoptosis. These effects were partially reversed by overexpression of GSTP1. Moreover, low-dose ionizing radiation increased GSTP1 gene methylation and downregulated GSTP1 expression. Furthermore, low-dose ionizing radiation affected the expression of GSTP1-related signaling molecules. CONCLUSIONS: This study shows that low-dose ionizing radiation damages GM12878 cells and affects their proliferation, cell cycle progression, and apoptosis. In addition, GSTP1 plays a modulating role under low-dose ionizing radiation damage conditions. Low-dose ionizing radiation affects the expression of Nrf2, JNK, and other signaling molecules through GSTP1.
Glutathione S-Transferase pi , Uranium , Adult , Humans , Glutathione S-Transferase pi/genetics , Radiation, Ionizing , Gamma Rays/adverse effects , Apoptosis
This study optimized the menaquinone-7 (MK-7) synthetic pathways in Bacillus subtilis (B. subtilis) natto NB205, a strain that originated from natto, to enhance its MK-7 production. Utilizing mutation breeding, we developed NBMK308, a mutant strain that demonstrated a significant 117.23% increase in MK-7 production. A comprehensive transcriptome analysis identified two key genes, ispA and ispE, as being critical in MK-7 synthesis. The dual-sgRNA CRISPRa system was utilized to achieve precise regulation of ispA and ispE in the newly engineered strain, A3E3. This strategic modulation resulted in a significant enhancement of MK-7 production, achieving increases of 20.02% and 201.41% compared to traditional overexpression systems and the original strain NB205, respectively. Furthermore, the fermentation supernatant from A3E3 notably inhibited Salmonella invasion in Caco-2 cells, showcasing its potential for combating such infections. The safety of the dual-sgRNA CRISPRa system was confirmed through cell assays. The utilization of the dual-sgRNA CRISPRa system in this study was crucial for the precise regulation of key genes in MK-7 synthesis, leading to a remarkable increase in production and demonstrating additional therapeutic potential in inhibiting pathogenic infections. This approach effectively combined the advantages of microbial fermentation and biotechnology, addressing health and nutritional challenges.
Salmonella Infections , Soy Foods , Humans , Bacillus subtilis/metabolism , RNA, Guide, CRISPR-Cas Systems , Caco-2 Cells , Fermentation , Salmonella Infections/prevention & control
It has been previously established that paternal development of a strong incentive motivation for cocaine can predispose offspring to develop high cocaine-seeking behavior, as opposed to sole exposure to the drug that results in drug resistance in offspring. However, the adaptive changes of the reward circuitry have not been fully elucidated. To infer the key nuclei and possible hub genes that determine susceptibility to addiction in offspring, rats were randomly assigned to three groups, cocaine self-administration (CSA), yoked administration (Yoke), and saline self-administration (SSA), and used to generate F1. We conducted a comprehensive transcriptomic analysis of the male F1 offspring across seven relevant brain regions, both under drug-naïve conditions and after cocaine self-administration. Pairwise differentially expressed gene analysis revealed that the orbitofrontal cortex (OFC) exhibited more pronounced transcriptomic changes in response to cocaine exposure, while the dorsal hippocampus (dHip), dorsal striatum (dStr), and ventral tegmental area (VTA) exhibited changes that were more closely associated with the paternal voluntary cocaine-seeking behavior. Consistently, these nuclei showed decreased dopamine levels, elevated neuronal activation, and elevated between-nuclei correlations, indicating dopamine-centered rewiring of the midbrain circuit in the CSA offspring. To determine if possible regulatory cascades exist that drive the expression changes, we constructed co-expression networks induced by paternal drug addiction and identified three key clusters, primarily driven by transcriptional factors such as MYT1L, POU3F4, and NEUROD6, leading to changes of genes regulating axonogenesis, synapse organization, and membrane potential, respectively. Collectively, our data highlight vulnerable neurocircuitry and novel regulatory candidates with therapeutic potential for disrupting the transgenerational inheritance of vulnerability to cocaine addiction.
Cocaine-Related Disorders , Cocaine , Rats , Male , Animals , Dopamine , Cocaine/adverse effects , Cocaine-Related Disorders/genetics , Cocaine-Related Disorders/metabolism , Reward , Gene Expression Profiling , Self Administration
