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Objective: The study aimed to compare the differences in the performance of seven session-rating of perceived exertion (RPE)-derived metrics (coupled and uncoupled acute: chronic workload ratio (ACWR), weekly ratio of workload change, monotony, standard deviation of weekly workload change, exponentially weighted moving average (EWMA), and robust exponential decreasing index (REDI)) in classifying the performance of an injury prediction model after taking into account the time series (no latency, 5-day latency, and 10-day latency). Design: The study documented the RPE of eight curlers in their daily training routine for 211 days prior to the Olympic Games. Methods: Seven Session-RPE (sRPE)-derived metrics were used to build models at three time series nodes using logistic regression and multilayer perceptron. Receiver operating characteristic plots were plotted to evaluate the model's performance. Results: Among the seven sRPE-derived metrics multilayer perceptron models, the model without time delay (same-day load corresponding to same-day injury) exhibited the highest average classification performance (86.5%, AUC = 0.773). EMWA and REDI demonstrated the best classification performance (84.4%, p < 0.001). Notably, EMWA achieved the highest classifying accuracy in the no-delay time series (90.0%, AUC = 0.899), followed by the weekly load change rate under the 5-day delay time series (88.9%, AUC = 0.841). Conclusion: EWMA without delay is a more sensitive indicator for detecting injury risk.
Subject(s)
Athletes , Athletic Injuries , Physical Exertion , Workload , Humans , Athletes/statistics & numerical data , Male , Workload/statistics & numerical data , Adult , Young Adult , Risk Assessment/methods , FemaleABSTRACT
It is well-accepted that multisensory integration (MSI) undergoes protracted maturation from childhood to adulthood. However, existing evidence may have been confounded by potential age-related differences in attention. To unveil neurodevelopmental changes in MSI while matching top-down attention between children and adults, we recorded event-related potentials of healthy children aged 7 to 9 years and young adults in the visual-to-auditory attentional spreading paradigm wherein attention and MSI could be measured concurrently. The absence of children versus adults differences in the visual selection negativity component and behavioral measures of auditory interference first demonstrates that the child group could maintain top-down visual attention and ignore task-irrelevant auditory information to a similar extent as adults. Then, the stimulus-driven attentional spreading quantified by the auditory negative difference (Nd) component was found to be overall absent in the child group, revealing the children's largely immature audiovisual binding process. These findings furnish strong evidence for the protracted maturation of MSI per se from childhood to adulthood, hence providing a new benchmark for characterizing the developmental course of MSI. In addition, we also found that the representation-driven attentional spreading measured by another Nd was present but less robust in children, suggesting their substantially but not fully developed audiovisual representation coactivation process.
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Background: Bladder cancer (BLCA) presents as a heterogeneous epithelial malignancy. Progress in the early detection and effective treatment of BLCA relies heavily on the identification of novel biomarkers. Therefore, the primary goal of this study is to pinpoint potential biomarkers for BLCA through the fusion of single-cell RNA sequencing and RNA sequencing assessments. Furthermore, the aim is to establish practical clinical prognostic models that can facilitate accurate categorization and individualized therapy for patients. Methods: In this research, training sets were acquired from the TCGA database, whereas validation sets (GSE32894) and single-cell datasets (GSE135337) were extracted from the GEO database. Single-cell analysis was utilized to obtain characteristic subpopulations along with their associated marker genes. Subsequently, a novel BLCA subtype was identified within TCGA-BLCA. Furthermore, an artificial neural network prognostic model was constructed within the TCGA-BLCA cohort and subsequently verified utilizing a validation set. Two machine learning algorithms were employed to screen hub genes. QRT-qPCR was performed to detect the gene expression levels utilized in the construction of prognostic models across various cell lines. Additionally, the cMAP database and molecular docking were utilized for searching small molecule drugs. Results: The results of single-cell analysis revealed the presence of epithelial cells in multiple subpopulations, with 1579 marker genes selected for subsequent investigations. Subsequently, four epithelial cell subtypes were identified within the TCGA-BLCA cohort. Notably, cluster A exhibited a significant survival advantage. Concurrently, an artificial neural network prognostic model comprising 17 feature genes was constructed, accurately stratifying patient risk. Patients categorized in the low-risk group demonstrated a considerable survival advantage. The ROC analysis suggested that the model has strong prognostic ability. Furthermore, the findings of the validation group align consistently with those from the training group. Two types of machine learning algorithms screened NFIC as hub genes. Forskolin, a small molecule drug that binds to NFIC, was identified by employing a cMAP database and molecular docking. Conclusion: The analysis results supplement the research on the role of epithelial cells in BLCA. An artificial neural network prognostic model containing 17 characteristic genes demonstrates the capability to accurately stratify patient risk, thereby potentially improving clinical decision-making and optimizing personalized therapeutic approaches.
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Calcium-overload-mediated tumor therapy has received considerable interest in oncology. However, its efficacy has been proven to be inadequate due to insufficient calcium ion concentration at the tumor site coupled with challenges in facilitating efficient calcium uptake by tumors, leading to unsatisfactory therapeutic outcomes. In the present study, calcium carbonate nanoshell mineralized ferric polydopamine nanoparticles (Fe-PDA@CaCO3 NPs) were prepared for achieving Ca2+-overload-mediated tumor therapy. Upon entering the tumor site, the pH-responsive CaCO3 layer, acting as a "Ca2+ storage pool", rapidly degraded and released high quantities of free Ca2+ within the weakly acidic environment. The Fe-PDA core, with its excellent photothermal conversion properties, could significantly increase the temperature upon exposure to near-infrared (NIR) light irradiation, thereby activating the TRPV1 channel and leading to a large influx of released Ca2+ into the cytoplasm. Furthermore, the exposed Fe-PDA core could react with the tumor-overexpressed hydrogen peroxide (H2O2) to efficiently produce hydroxyl radicals (â¢OH), significantly increasing intracellular reactive oxygen species (ROS) levels and thus inhibiting the activity of the Ca2+ efflux pump, resulting in a high intracellular Ca2+ concentration. Ultimately, the increase in calcium/ROS levels could disrupt mitochondrial homeostasis and activate the apoptosis pathway. The current work presents a promising approach for tumor therapy using photothermal-enhanced calcium-overload-mediated ion interference therapy and chemodynamic therapy.
Subject(s)
Calcium Carbonate , Calcium , Indoles , Nanoparticles , Polymers , Reactive Oxygen Species , Calcium Carbonate/chemistry , Indoles/chemistry , Indoles/pharmacology , Animals , Calcium/chemistry , Calcium/metabolism , Mice , Polymers/chemistry , Polymers/pharmacology , Humans , Nanoparticles/chemistry , Reactive Oxygen Species/metabolism , Hydrogen-Ion Concentration , Cell Line, Tumor , Infrared Rays , Iron/chemistry , Photothermal Therapy , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Hydrogen Peroxide/chemistry , Mice, Inbred BALB C , Neoplasms/therapy , Neoplasms/drug therapy , Neoplasms/pathology , Neoplasms/metabolismABSTRACT
A simple and efficient dual-signal electrochemical sensor was designed for glyphosate (GLYP) determination based on the one-step electro-synthesized Cu-Hemin MOFs/CNTs nanocrystals. Cu-Hemin MOFs/CNTs were directly modified on the electrode through electrodeposition, avoiding complicated synthesis and modification processes. The incorporation of CNTs greatly boosted the conductivity of Cu-Hemin MOFs and the sensitivity of the electrochemical sensor. Cu active sites in Cu-Hemin MOFs were converted to CuCl, allowing the specific detection of GLYP with the turn of CuCl into non-electroactive Cu-GLYP. Meanwhile, GLYP showed highly effective inhibition effect on the inherent peroxidase-like activity of Cu-Hemin MOFs, therefore generating the second electrochemical signal with Cu-Hemin MOFs-catalyzed o-phenylenediamine (o-PD) + H2O2 system. The Cu-Hemin MOFs/CNTs based sensor with two electrochemical signals showed good linearities of 1.0 × 10-10 M - 3.0 × 10-6 M and 1.0 × 10-10 M - 5.0 × 10-5 M, with detection limits of 5.17 × 10-12 M and 6.81 × 10-12 M for the CuCl signal based assay and nanozyme catalyzed o-PD + H2O2 procedure, respectively. This simple and robust dual-signal sensor with excellent selectivity, accuracy, and stability allowed GLYP quantification in real samples, highlighting the potential application of this approach for food and environmental monitoring.
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Feeding silkworms with functional materials as additives to produce naturally modified silk is a facile, diverse, controllable, and environmentally friendly method with a low cost of time and investment. Among various additives, carbon dots (CDs) show unique advantages due to their excellent biocompatibility and fluorescence stability. Here, a new type of green fluorescent carbon dots (G-CDs) is synthesized with a high oil-water partition ratio of 147, a low isoelectric point of 5.16, an absolute quantum yield of 71%, and critically controlled surface states. After feeding with G-CDs, the silkworms weave light yellow cocoons whose green fluorescence is visible to the naked eye under UV light. The luminous silk is sewn onto the cloth to create striking patterns with beautiful fluorescence. Such G-CDs have no adverse effect on the survival rate and the life cycle of silkworms and enable their whole bodies to glow under UV light. Based on the strong fluorescence, chemical stability, and biological safety, G-CDs are found in the digestive tracts, silk glands, feces, cocoons, and even moth bodies. G-CDs accumulate in the posterior silk glands where fibroin protein is secreted, indicating its stronger combination with fibroin than sericin, which meets the requirements for practical applications.
Subject(s)
Bombyx , Carbon , Quantum Dots , Silk , Animals , Silk/chemistry , Carbon/chemistry , Quantum Dots/chemistry , Fibroins/chemistry , Ultraviolet Rays , Fluorescence , Fluorescent Dyes/chemistry , Surface PropertiesABSTRACT
Achieving selective detection of ppb-level CO is important for air quality testing at industrial sites to ensure personal safety. Noble metal doping enhances charge transfer, which in turn reduces the detection limit of metal oxide gas sensors. In this work, metal-organic framework-derived Au-doped In2O3 nanotubes with high electrical conductivity are synthesized by pyrolysis of the Au-doped metal-organic framework (In-MIL-68) as a template. Gas-sensing experiments reveal that the detection limit of 0.2% Au-doped In2O3 nanotubes (0.2% Au, mass fraction) is as low as 750 ppb. Meanwhile, the sensing material shows a response value of 18.2 to 50 ppm of CO at 240 °C, which is about 2.8 times higher than that of pure In2O3. Meanwhile, the response and recovery times are short (37 s/86 s). The gas-sensing mechanism of CO is uncovered by in situ DRIFTS through the reaction intermediates. In addition, first-principles calculations suggest that Au doping of In2O3 significantly enhances its adsorption energy for CO and improves the electron transfer properties. This study reveals a novel synthesis pathway for Au-doped In2O3 nanotubular structures and their potential application in low concentration CO detection.
Subject(s)
Carbon Monoxide , Gold , Indium , Metal-Organic Frameworks , Nanotubes , Gold/chemistry , Metal-Organic Frameworks/chemistry , Nanotubes/chemistry , Indium/chemistry , Carbon Monoxide/analysis , Limit of DetectionABSTRACT
Chemodynamic therapy (CDT) is a novel tumor treatment method by using hydroxyl radicals (â¢OH) to kill cancer cells. However, its therapeutic effects are strictly confined by the short lifespan of â¢OH and reduced â¢OH generation speed. Herein, an effective CDT is achieved by both improving â¢OH lifetime and long-lasting generating â¢OH through intraparticle electron transfer within heterogeneous nanoparticles (NPs). These heterogeneous NPs are composed of evenly distributed Cu and Fe3O4 (CFO NPs) with large interaction interfaces, and electrons tend to transfer from Cu to Fe3O4 for the appearance of ≡Cu2+ and increase in ≡Fe2+. The generated ≡Cu2+ can interact with GSH, which prolongs the lifespan of â¢OH, produces ≡Cu+ for higher speed â¢OH generation with H2O2, and induces cell ferroptosis for tumor therapy. The improved ≡Fe2+ can also improve the â¢OH release under H2O2 until Cu is depleted. As a result, a sustainable â¢OH generation is achieved to promote cell apoptosis for effective tumor therapy. Since H2O2 and GSH are only overexpressed at tumor, and CFO NPs can degrade in the tumor microenvironment, these NPs are with high biosafety and can be metabolized by urine. This work provides a novel biomaterial for effective cancer CDT through intraparticle electron transfer.
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Background: Osteoporosis remains substantially underdiagnosed and undertreated worldwide. Chest low-dose computed tomography (LDCT) may provide a valuable and popular opportunity for osteoporosis screening. This study sought to evaluate the feasibility of the screening of low bone mineral density (BMD) and osteoporosis with mean attenuation values of the lower thoracic compared to upper lumbar vertebrae. The cutoff thresholds of the mean attenuation values in Hounsfield units (HU) were derived to facilitate implementation of opportunistic screening using chest LDCT. Methods: The participants aged 30 years or older who underwent chest LDCT and quantitative computed tomography (QCT) examinations from August 2018 to October 2020 in our hospital were consecutively included in this retrospective study. A region of interest (ROI) was placed in the trabecular bone of each vertebral body to measure the HU values. The correlations of mean HU values of lower thoracic (T11-T12) and upper lumbar (L1-L2) vertebrae with age and lumbar BMD obtained with QCT were performed using the Pearson correlation coefficient, respectively. The area under the curve (AUC) of the receiver operator characteristic (ROC) curve was generated to determine the cutoff thresholds for distinguishing low BMD from normal and osteoporosis from non-osteoporosis. Results: A total of 1,112 participants were included in the final study cohort (743 men and 369 women, mean age 58.2±8.9 years; range, 32-88 years). The mean HU values of T11-T12 and L1-L2 were significantly different among 3 QCT-defined BMD categories of osteoporosis, osteopenia, and normal (P<0.001). The differences in HU values between T11-T12 and L1-L2 in each category of bone status were statistically significant (P<0.001). The mean HU values of T11-T12 (r=-0.453, P<0.001) and L1-L2 (r=-0.498, P<0.001) had negative correlations with age. Positive correlations were observed between the mean HU values of T11-T12 (r=0.872, P<0.001) and L1-L2 (r=0.899, P<0.001) with BMD. The optimal cutoff thresholds for distinguishing low BMD from normal were average T11-T12 ≤157 HU [AUC =0.941, 95% confidence interval (CI): 0.925-0.954, P<0.001] and L1-L2 ≤138 HU (AUC =0.950, 95% CI: 0.935-0.962, P<0.001), as well as distinguishing osteoporosis from non-osteoporosis were average T11-T12 ≤125 HU (AUC =0.960, 95% CI: 0.947-0.971, P<0.001) and L1-L2 ≤107 HU (AUC =0.961, 95% CI: 0.948-0.972, P<0.001). There was no significant difference between the AUC values of T11-T12 and L1-L2 for low BMD (P=0.07) and osteoporosis (P=0.92) screening. Conclusions: We have conducted a study on low BMD and osteoporosis screening using mean attenuation values of lower thoracic and upper lumbar vertebrae. Assessment of mean attenuation values of T11-T12 and L1-L2 can be used interchangeably for low BMD and osteoporosis screening using chest LDCT, and their cutoff thresholds were established.
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Background: Biliary atresia (BA) is a devastating congenital disease characterized by inflammation and progressive liver fibrosis. Activation of hepatic stellate cells (HSCs) plays a central role in the pathogenesis of hepatic fibrosis. Our study aimed to investigate the pharmacological effect and potential mechanism of pirfenidone (PFD) and andrographolide (AGP) separately and together on liver fibrosis of BA. Materials and Methods: The bile ducts of male C57BL/6J mice were ligated or had the sham operation. The in vivo effects of PFD and/or AGP on liver fibrosis of BA were evaluated. Human hepatic stellate cells (LX-2) were also treated with PFD and/or AGP in vitro. Results: PFD and/or AGP ameliorates liver fibrosis and inflammation in the mice model of BA, as evidenced by significant downregulated in the accumulation of collagen fibers, hepatic fibrosis markers (α-SMA, collagen I, and collagen IV), and inflammatory markers (IL-1ß, IL-6, and TNF-α). Moreover, compared with monotherapy, these changes are more obvious in the combined treatment of PFD and AGP. Consistent with animal experiments, hepatic fibrosis markers (α-SMA, collagen I, and CTGF) and inflammatory markers (IL-1ß, IL-6, and TNF-α) were significantly decreased in activated LX-2 cells after PFD and/or AGP treatment. In addition, PFD and/or AGP inhibited the activation of HSCs by blocking the TGF-ß/Smad signaling pathway, and the combined treatment of PFD and AGP synergistically inhibited the phosphorylation of Smad2 and Smad3. Conclusion: The combined application of PFD and AGP exerted superior inhibitive effects on HSC activation and liver fibrosis by mediating the TGF-ß/Smad signaling pathway as compared to monotherapy. Therefore, the combination of PFD and AGP may be a promising treatment strategy for liver fibrosis in BA.
Subject(s)
Diterpenes , Hepatic Stellate Cells , Liver Cirrhosis , Mice, Inbred C57BL , Pyridones , Signal Transduction , Smad Proteins , Transforming Growth Factor beta , Hepatic Stellate Cells/drug effects , Hepatic Stellate Cells/metabolism , Hepatic Stellate Cells/pathology , Animals , Liver Cirrhosis/pathology , Liver Cirrhosis/drug therapy , Liver Cirrhosis/metabolism , Signal Transduction/drug effects , Diterpenes/pharmacology , Diterpenes/therapeutic use , Male , Transforming Growth Factor beta/metabolism , Smad Proteins/metabolism , Humans , Pyridones/pharmacology , Cell Line , Mice , Biliary Atresia/pathology , Biliary Atresia/drug therapy , Biliary Atresia/metabolism , Disease Models, Animal , Drug Therapy, CombinationABSTRACT
This review aimed to systematically investigate the intracellular and subcellular fate of various types of targeting carriers. Upon entering the body via intravenous injection or other routes, a targeting carrier that can deliver therapeutic agents initiates their journey. If administered intravenously, the carrier initially faces challenges presented by the blood circulation before reaching specific tissues and interacting with cells within the tissue. At the subcellular level, the car2rier undergoes processes, such as drug release, degradation, and metabolism, through specific pathways. While studies on the fate of 13 types of carriers have been relatively conclusive, these studies are incomplete and lack a comprehensive analysis. Furthermore, there are still carriers whose fate remains unclear, underscoring the need for continuous research. This study highlights the importance of comprehending the in vivo and intracellular fate of targeting carriers and provides valuable insights into the operational mechanisms of different carriers within the body. By doing so, researchers can effectively select appropriate carriers and enhance the successful clinical translation of new formulations.
Nowadays, scientists are actively researching nanocarrier drugs. After administration via injection or other methods, these drugs experience in the body and reach the target treatment site to relieve or cure symptoms. As research progresses, scientists are gaining more insights into the behavior of nanocarrier drugs in the body, which is useful in developing safer and more effective drugs. Historically, research has focused primarily on the drug itself. However, it is important to understand that the carrier that delivers and protects the drug (often described as the drug sitting in a "car" or under an "umbrella") plays an essential role in the drug's therapeutic effect. This paper aims to highlight the importance of the carrier's role, which is vital for developing new drugs and advancing basic research.
Subject(s)
Drug Carriers , Drug Delivery Systems , Humans , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Animals , Drug Delivery Systems/methods , Nanoparticles/chemistry , Drug LiberationABSTRACT
Mitochondria and endoplasmic reticulum contacts (MERCs) control multiple cellular processes, including cell survival and differentiation. Based on the observations that MERCs were specifically enriched in the CD4-CD8- double-negative (DN) stage, we studied their role in early mouse thymocyte development. We found that T cell-specific knockout of Hspa9, which encodes GRP75, a protein that mediates MERC formation by assembling the IP3R-GRP75-VDAC complex, impaired DN3 thymocyte viability and resulted in thymocyte developmental arrest at the DN3-DN4 transition. Mechanistically, GRP75 deficiency induced mitochondrial stress, releasing mitochondrial DNA (mtDNA) into the cytosol and triggering the type I interferon (IFN-I) response. The IFN-I pathway contributed to both the impairment of cell survival and DN3-DN4 transition blockage, while increased lipid peroxidation (LPO) played a major role downstream of IFN-I. Thus, our study identifies the essential role of GRP75-dependent MERCs in early thymocyte development and the governing facts of cell survival and differentiation in the DN stage.
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Sensitive and accurate determination of glyphosate (GLYP) is vital for food safety and environmental protection. Herein, a novel electrochemical ratiometric biosensor was designed for the accurate quantification of GLYP through one-step electrodeposition of MWCNTs-Cu MOF films. MWCNTs-Cu MOF nanostructures were directly electro-synthesized in situ on the electrode from the precursor solution. The combination of Cu MOFs with MWCNTs not merely improved the conductivity of MOFs, but also enhanced the sensitivity of the biosensor. Furthermore, Cu sites within Cu MOFs were turned into CuCl to further amplify the current signal and enable the specific recognition of GLYP through competing reactions with the transformation of CuCl into non-electroactive Cu-GLYP. Meanwhile, internal reference molecules of methylene blue (MB) were incorporated to improve the measurement accuracy of GLYP for reducing unpredictable measurement errors aroused by environmental deviations. The ratiometric electrochemical sensor exhibited a high linearity with the logarithmic value of GLYP concentration from 0.5 nM to 400 nM. The detection limit was estimated to be as low as 0.014 nM. Finally, the present sensor with ratiometric signal export was applied for GLYP analysis in real samples with high sensitivity and accuracy. The simplicity and reliability of the ratiometric sensor make it a worthy and powerful tool for food and environmental monitoring. This design strategy also provides an avenue for the development of simple and efficient biosensors for other substances.
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Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant disease that can give rise to the formation of vascular lesions in affected individuals. These lesions, whether occurring spontaneously or as a result of trauma, have the potential to cause severe and even fatal hemorrhage. Case description: We presented a case demonstrating the most extensive hematoma ever documented in a patient with NF1, resulting from a minor trauma. He experienced hemodynamic instability due to severe anemia. Arteriography revealed a rupture in the intercostal artery, which was successfully treated through interventional embolization to stop the hemorrhage. Additionally, we implemented a refined surgical approach, beginning with suturing, followed by the meticulous resection of necrotic and aberrant tissues, thereby markedly diminishing bleeding. Conclusion: Minor trauma may cause severe bleeding in patients with NF1, which can be life-threatening. Timely diagnosis of NF1 and effective hemostatic techniques are key to successful treatment.
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BACKGROUND: This study aimed to investigate the clinical value and prognostic significance of the alanine aspartate aminotransferase-to-lymphocyte ratio index (ALRI) in patients diagnosed with acute myocardial infarction (AMI). METHODS: Clinical indices of patients with AMI were collected from the Medical Information Mark for Intensive Care (MIMIC) III database and Wuhan Sixth Hospital. Cox regression analysis was used to explore whether ALRI was a risk factor for a worse prognosis in patients with AMI, and a nomogram including ALRI was created to estimate its predictive performance for 28-day mortality. RESULTS: Based on clinical data from the MIMIC-III database, we found that a high ALRI was closely associated with a variety of clinical parameters. It was an important risk factor for 28-day survival in patients with AMI (HR = 5.816). ALRI had a high predictive power for worse 28-day survival in patients with AMI (area under the curve [AUC] = 0.754). Additionally, we used clinical data from the Wuhan Sixth Hospital to verify the predictive power of ALRI in patients with AMI, and a high level of ALRI remained an independent risk factor for worse survival in patients with AMI (HR = 4.969). The AMI nomogram, including ALRI, displayed a good predictive performance for 28-day mortality in both the MIMIC-III (AUC = 0.826) and Wuhan Sixth Hospital cohorts (AUC = 0.795). CONCLUSION: The ALRI is closely related to the survival outcomes of patients with newly diagnosed AMI, indicating that it could serve as a novel biomarker for risk stratification such patients.
Subject(s)
Aspartate Aminotransferases , Lymphocytes , Myocardial Infarction , Humans , Myocardial Infarction/mortality , Myocardial Infarction/blood , Myocardial Infarction/diagnosis , Male , Female , Prognosis , Middle Aged , Aspartate Aminotransferases/blood , Aged , Nomograms , Risk Factors , Lymphocyte Count , Biomarkers/bloodABSTRACT
Objective: Helicobacter pylori (H. pylori) plays a major role in causing and advancing gastrointestinal illnesses. Our aim is to analyze the unique makeup and functional changes in the gastric microbiota of patients with chronic non-atrophic gastritis (CNAG), regardless of the presence of H. pylori, and to determine the potential signaling pathways. Methods: We performed metagenomic sequencing on gastric mucosa samples collected from 17 individuals with non-atrophic gastritis, comprising 6 cases were infected with H. pylori (H. pylori-infected case group) and 11 cases without (control group). The species composition was evaluated with DIAMOND software, and functional enrichment was assessed utilizing the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We analyzed antibiotic resistance patterns using the Comprehensive Antibiotic Resistance Database as a reference (CARD). Results: The presence of H. pylori colonization in CNAG patients was associated with increased diversity in the gastric microbiota. The Phylum Firmicutes was found to be less prevalent, while the Phylum Proteobacteria showed an increase. Functionally, pathways associated with metabolic pathways, including vitamins, auxiliaries, amino acid residue, carbon hydrate, and metabolic energy pathways, were enriched in CNAG patients with H. pylori infection. Additionally, antibiotic resistance genes correlated with antibiotic efflux pump were enriched. Conclusions: From a holistic genomic perspective, our findings offer fresh perspectives into the gastric microbiome among CNAG patients carrying H. pylori, which is valuable for future research on CNAG.
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Attentional bias toward weight-related stimuli plays a crucial role in the development and maintenance of body image disturbances. However, the temporal dynamics of attentional biases responsible for the previously reported behavioral effects caused by the task-irrelevant but spatial-relevant weight-related stimuli presented in the peripheral visual field among females with high weight dissatisfaction (HWD) remain unclear. The present study combined the modified dot-probe task and event-related potentials to explore the temporal dynamics of spatial attentional biases toward weight-related words among females with HWD. The results showed significantly larger N2pc amplitudes were elicited by fat-related and thin-related words than neutral words only in the HWD group. Moreover, only fat-related words elicited a significant PD for the HWD group, and the PD amplitudes were larger in the HWD group than in the control group. These findings revealed that weight-related words initially captured spatial allocation among females with HWD, and then fat-related words were actively suppressed after the initial capturing.
Subject(s)
Attentional Bias , Electroencephalography , Evoked Potentials , Humans , Female , Young Adult , Attentional Bias/physiology , Evoked Potentials/physiology , Body Weight/physiology , Body Dissatisfaction/psychology , Adult , Reaction Time/physiology , Space Perception/physiology , Photic Stimulation/methods , Attention/physiologyABSTRACT
BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of death in the USA, and high blood pressure is a major risk factor for CVD. Despite the overall declining rates of CVD mortality in the USA in recent years, marked disparities between racial and ethnic groups persist, with black adults having a higher mortality rate than white adults. We investigated the extent to which blood pressure mediated the black-white disparity in CVD mortality. METHODS: Data came from the Multi-Ethnic Study of Atherosclerosis, a diverse longitudinal cohort. We included 1325 black and 2256 white community-based adults aged 45-80 years free of clinical CVD at baseline and followed for 14 years. We used causal mediation analysis to estimate the effect of race on CVD mortality that was mediated through blood pressure. RESULTS: Black participants had a higher hazard of dying from CVD compared with white participants (adjusted hazard ratio (HR): 1.28 (95% CI 0.88, 1.88)), though estimates were imprecise. Systolic blood pressure mediated 27% (HR: 1.02, 95% CI 1.00, 1.06) and diastolic blood pressure mediated 55% (HR: 1.07, 95% CI 1.01, 1.10) of the racial disparities in CVD mortality between white and black participants. Mediation effects were present in men but not in women. CONCLUSIONS: We found that black-white differences in blood pressure partially explain the observed black-white disparity in CVD mortality, particularly among men. Our findings suggest that public health interventions targeting high blood pressure prevention and management could be important strategies for reducing racial disparities in CVD mortality.
Subject(s)
Black or African American , Blood Pressure , Cardiovascular Diseases , Health Status Disparities , Hypertension , White People , Humans , Male , Female , Middle Aged , Aged , White People/statistics & numerical data , Cardiovascular Diseases/mortality , Cardiovascular Diseases/ethnology , Black or African American/statistics & numerical data , Aged, 80 and over , United States/epidemiology , Hypertension/mortality , Hypertension/ethnology , Mediation Analysis , Longitudinal Studies , Risk FactorsABSTRACT
The human voltage-gated sodium channel Nav1.7 is a widely proven target for analgesic drug studies. ProTx2, a 30-residue polypeptide from Peruvian green tarantula venom, shows high specificity to activity against human Nav1.7, suggesting its potential to become a non-addictive analgesic. However, its high sensitivity to human Nav1.4 raises concerns about muscle side effects. Here, we engineered three mutants (R13A, R13D, and K27Y) of ProTx2 to evaluate their pharmacological activities toward Nav1.7 and Nav1.4. It is demonstrated that the mutant R13D maintained the analgesic effect in mice while dramatically reducing its muscle toxicity compared with ProTx2. The main reason is the formation of a strong electrostatic interaction between R13D and the negatively charged amino acid residues in DII/S3-S4 of Nav1.7, which is absent in Nav1.4. This study advances our understanding and insights on peptide toxins, paving the way for safer, effective non-addictive analgesic development.
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This study aimed to investigate the impact of three cooking ways (sous vide (SV), frying (FR) and roasting (RO)) on pork protein digestion characteristics under conditions simulating healthy adult (control, C) and elderly individuals with achlorhydria (EA). Changes in degree of hydrolysis (DH), SDS-PAGE profiles, zeta potential, particle size and secondary structure during digestion were evaluated. Our results revealed the EA condition markedly affected the protein digestion process of pork with different cooking ways. The DH values of SV (25.62%), FR (21.38%) and RO (19.40%) under the EA condition were significantly lower than those of under the control condition (38.32%, 33.00% and 30.86%, respectively). Moreover, differences were also observed among three cooking ways under the EA condition. For a given cooking way, the differences between control and EA conditions gradually diminished from the gastric to the intestinal phase. Under a certain digestion condition, SV maintained the highest degree of digestion throughout the process, particularly under the EA condition. Therefore, we conclude that pork cooked by sous vide is more recommendable for the elderly considering protein digestibility.