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Background: ATP11A, a P-type ATPase, functions as flippases at the plasma membrane to maintain cellular function and vitality in several cancers. However, the role of ATP11A in gastric cancer remains unknown. This study aimed to identify ATP11A related to the biological behavior of gastric cancer, and elucidate the underlying mechanism. Methods: The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were used to analyze the expression and prognosis of ATP11A. The biofunctions of ATP11A were explored through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA). The expression of ATP11A were validated by immunohistochemistry (IHC), qRT-PCR and Western blotting. Transwell, wound healing, CCK8 and colony-formation were to detected the migration, invasion and proliferation of gastric cancer cells. The epithelial-mesenchymal transition (EMT) and Hippo pathway markers were examined by Western blotting. Results: The expression of ATP11A was higher in gastric cancer tissues than in normal tissues, and high ATP11A levels were related to worse prognosis of gastric cancer patients. Additionally, we proved that ATP11A promoted the migration, invasion and proliferation in gastric cancer cells. Furthermore, ATP11A was found to promote EMT by devitalizing the Hippo pathway. Conclusion: ATP11A promoted migration, invasion, proliferation and EMT via Hippo signaling devitalization in gastric cancer cells.

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Plants encounter numerous adversities during growth, necessitating the identification of common stress activators to bolster their resistance. However, the current understanding of these activators' mechanisms remains limited. This study identified three anti-stress activators applicable to apple trees, all of which elevate plant proline content to enhance resistance against various adversities. The results showed that the application of these sugar substitutes increased apple proline content by two to three times compared to the untreated group. Even at a lower concentration, these activators triggered plant stress resistance without compromising apple fruit quality. Therefore, these three sugar substitutes can be exogenously sprayed on apple trees to augment proline content and fortify stress resistance. Given their effectiveness and low production cost, these activators possess significant application value. Since they have been widely used in the food industry, they hold potential for broader application in plants, fostering apple industry development.

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The study herein evaluated and compared the efficacy of Clear Aligners (CA) and Twin-Block (TB) appliances as the early orthodontic treatments of developing class II division 1 malocclusion. Twenty-four patients each for CA (11.73 ± 0.33 y) and TB (11.87 ± 0.34 y) groups were selected according to the inclusion and exclusion criteria. The cephalometric X-rays and intraoral photos were taken for the patients after nearly 12 months of treatment. Treatment impacts were evaluated by the molar correction and overjet reduction. The vertical and sagittal changes were analyzed through cephalometric measurements. Sella-nasion-point B angle (SNB), point A-nasion-point B angle (ANB), Wits Appraisal (AO-BO) and overjet were statistically significant regarding the sagittal changes analyzed before and after the treatments in both groups, respectively. So, no significant difference was noted in the sagittal changes between CA and TB groups. However, for the vertical changes, OP (occlusal plane) angle of CA group and OP angle, AFH (anterior facial height) and PFH (posterior facial height) of TB group were statistically significant. Moreover, the Z angle and cranial facial difficulty (C.F. difficulty) were also statistically significant in both groups. Class II children with retrognathic mandible are effectively treated by employing the CA, which has almost the same impact as of TB in sagittal and vertical changes. Resultantly, the patient profile is improved. The CA and TB treatments thus minimize the subsequent treatment difficulty by reducing the C.F. difficulty.

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Abnormally elevated tumor necrosis factor-α (TNFα) levels at the maternal-fetal interface can lead to adverse pregnancy outcomes, including recurrent miscarriage (RM), but the mechanism underlying upregulated TNFα expression is not fully understood. We previously reported that the interaction between monoclonal nonspecific suppressor factor-ß (MNSFß) and RC3H1 upregulates TNFα expression, but the precise mechanisms are unknown. In this study, we found that MNSFß stimulated the LPS-induced TNFα expression by inactivating the promoting effect of RC3H1 on TNFα mRNA degradation rather than directly inhibiting the expression of RC3H1 in THP1-Mϕs. Mechanistically, the 81-326 aa region of the RC3H1 protein binds to the 101-133 aa region of the MNSFß protein, and MNSFß facilitated stress granules (SGs) formation and the translocation of RC3H1 to SGs by interacting with RC3H1 and fragile X mental retardation 1 (FMR1) in response to LPS-induced stress. The SGs-localization of RC3H1 reduced its inhibitory effect on TNFα expression in LPS-treated THP1-Mϕs. The designed HEPN2 peptide effectively reduced the LPS-induced expression of TNFα in THP1-Mϕs by interfering with the MNSFß-RC3H1 interaction. Treatment with the HEPN2 peptide significantly improved adverse pregnancy outcomes, including early pregnancy loss (EPL) and lower fetal weight (LFW), which are induced by LPS in mice. These data indicated that MNSFß promoted TNFα expression at least partially by increasing the localization of RC3H1 to SGs under inflammatory stimulation and that the HEPN2 peptide improved the adverse pregnancy outcomes induced by LPS in mice, suggesting that MNSFß is a potential pharmacological target for adverse pregnancy outcomes caused by abnormally increased inflammation at early pregnancy.

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Background: Temporomandibular joint disorders (TMD) are highly prevalent among people. Numerous investigations have revealed the impact of gut microbiota in many diseases. However, the causal relationship between Temporomandibular joint disorders and gut microbiota remains unclear. Methods: Genome-Wide Association Studies (GWAS) refer to the identification of sequence variations, namely single nucleotide polymorphisms (SNPs), existing across the entire human genome. GWAS data were collected on gut microbiota and TMD. Then, instrumental variables were screened through F-values and removal of linkage disequilibrium. These SNPs underwent mendelian analysis using five mathematical models. Sensitivity analysis was conducted to further verify the stability of the results. Pathogenic factors of TMD mediate the causal relationship between gut microbiota and TMD were explored through a two-step Mendelian randomization analysis. Finally, reverse mendelian analysis was conducted to account for potential reverse effects. Results: The analysis of the data in this article suggests that some gut microbiota, including Coprobacter, Ruminococcus torques group, Catenibacterium, Lachnospiraceae, Turicibacter, Victivallis, MollicutesRF9, Methanobacteriales, Methanobacteriaceae, FamilyXI, Methanobacteria were identified as risk factors, while Peptococcaceae provides protection for TMD. Conclusion: The research reveals the relation of gut microbiota in TMD. These findings provide insights into the underlying mechanisms and suggest potential therapeutic strategy.

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The widespread sulfonamide resistance genes sul1, sul2, and sul3 in food and gut bacteria have attracted considerable attention. In this study, we assessed the in vivo fitness of sul gene-dependent sulfonamide-resistant Escherichia coli, using a murine model. High fitness costs were incurred for sul1 and sul3 gene-dependent E. coli strains in vivo. A fitness advantage was found in three of the eight mice after intragastric administration of sul2 gene-dependent E. coli strains. We isolated three compensatory mutant strains (CMSs) independently from three mice that outcompeted the parent strain P2 in vivo. Whole-genome sequencing revealed seven identical single nucleotide polymorphism (SNP) mutations in the three CMSs compared with strain P2, an additional SNP mutation in strain S2-2, and two additional SNP mutations in strain S2-3. Furthermore, tandem mass tag-based quantitative proteomic analysis revealed abundant differentially expressed proteins (DEPs) in the CMSs compared with P2. Of these, seven key fitness-related DEPs distributed in two-component systems, galactose and tryptophan metabolism pathways, were verified using parallel reaction monitoring analysis. The DEPs in the CMSs influenced bacterial motility, environmental stress tolerance, colonization ability, carbohydrate utilization, cell morphology maintenance, and chemotaxis to restore fitness costs and adapt to the mammalian gut environment.IMPORTANCESulfonamides are traditional synthetic antimicrobial agents used in clinical and veterinary medical settings. Their long-term excessive overuse has resulted in widespread microbial resistance, limiting their application for medical interventions. Resistance to sulfonamides is primarily conferred by the alternative genes sul1, sul2, and sul3 encoding dihydropteroate synthase in bacteria. Studying the potential fitness cost of these sul genes is crucial for understanding the evolution and transmission of sulfonamide-resistant bacteria. In vitro studies have been conducted on the fitness cost of sul genes in bacteria. In this study, we provide critical insights into bacterial adaptation and transmission using an in vivo approach.

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To evaluate the measurement accuracy of horizontal and vertical remote emission sensing (RES) equipment, a real-world dynamic test was carried out in Chengdu by using electric vehicles equipped with various concentrations of standard gases. In addition, a new Image-based Spectral Processing Algorithm (ISPA) for vertical remote sensing spectral data was developed to improve the measurement capability. The results showed that the ISPA provided a greater percentage of valid data and lower relative errors; thus, our new algorithm could more effectively analyze the spectral data to measure vehicle emission levels. The percentages of valid horizontal and vertical RES data were 71% and 84%, respectively. The mean relative errors of CO2, CO, HC and NO measured by the vertical RES were about 5%, 20%, 20% and 40%, respectively, and those of CO2, CO and NO measured by the horizontal RES were 3%, 13% and 15%, respectively. For the common vehicle emission concentration, the percentage of valid data for the two RES types increased with increasing gas concentration. As the vehicle speed increased, the relative errors of the horizontal RES equipment showed an increasing trend for the same concentration of gas. Furthermore, for the same speed segment, the relative errors of the horizontal RES equipment increased as the simulated emission concentration decreased. The vertical RES equipment did not exhibit a consistent trend in terms of changes. This study provides a data quality reference for further RES applications.

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Epithelial-derived cytokines, especially type 2 alarmins (TSLP, IL-25, and IL-33), have emerged as critical mediators of type 2 inflammation. IL-33 attracts more interest for its strong association with allergic asthma, especially in childhood asthma. However, the age-dependent role of IL-33 to the development of allergic asthma remains elusive. Here, using OVA-induced allergic asthma model in neonatal and adult mice, we report that IL-33 is the most important alarmin in neonatal lung both at steady state or inflammation. The deficiency of IL-33/ST2 abrogated the development of allergic asthma only in neonates, whereas in adults the effect was limited. Interestingly, the deficiency of IL-33/ST2 equally dampened the ILC2 responses in both neonatal and adult models. However, the effect of IL-33/ST2 deficiency on Th2 responses is age-dependent, which is only blocked in neonates. Furthermore, IL-33/ST2 signaling is dispensable for OVA sensitization. Following OVA challenge in adults, the deficiency of IL-33/ST2 results in compensational more TSLP, which in turn recruits and activates lung DCs and boosts Th2 responses. The enriched γδ T17 cells in IL-33/ST2 deficient neonatal lung suppress the expression of type 2 alarmins, CCL20 and GM-CSF via IL-17A, thus might confer the inhibition of allergic asthma. Finally, on the basis of IL-33 deficiency, the additive protective effects of TSLP blocking is much more pronounced than IL-25 blocking in adults. Our studies demonstrate that the role of IL-33 for ILC2 and Th2 responses varies among ages in OVA models and indicate that the factor of age should be considered for intervention of asthma.

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Gaseous nitrous acid (HONO), playing a crucial role in the generation of hydroxyl (OH) radicals and thus secondary pollution, lacks a source. Vehicular emission is a significant HONO source and is usually estimated by a traditional estimation indicator (RHONO/NOx = 0.8 %). Nevertheless, with more direct measurements for vehicular HONO emissions, RHONO/NOx values have been reported to vary over a wide range. In this study, we conducted the driving tests with a chassis dynamometer for ten light-duty gasoline vehicles. HONO emission factors have realized a significant reduction with the updating of emission standards, with emission factors of 0.40 mg/km, 0.13 mg/km, and 0.06 mg/km for China IV, China V, and China VI vehicles, respectively. Besides precursors, water content and exhaust temperature were found to be possible decisive factors for initiating HONO generation. Furthermore, by coupling NOx emissions and combustion efficiency, we modified the estimation indicator for vehicular HONO emissions and a better estimation effect has been verified. Additionally, we established a dynamic inventory of vehicular HONO emissions in Jinniu District in Chengdu and further found the traditional estimation indicator would overestimate HONO emissions by around 17 %. Our findings would help to advance a deeper understanding of vehicular HONO emissions and the modified estimation indicator would be beneficial in minimizing the uncertainties of the HONO budget in the troposphere.

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Timely screening for harmful pathogens is a great challenge in emergencies where traditional culture methods suffer from long assay time and alternative methods are limited by poor accuracy and low robustness. Herein, we present a dCas9-mediated colorimetric and surface-enhanced Raman scattering (SERS) dual-signal platform (dCas9-CSD) to address this challenge. Strategically, the platform used dCas9 to accurately recognize the repetitive sequences in amplicons produced by loop-mediated isothermal amplification (LAMP), forming nucleic acid frameworks that assemble numerous bifunctional gold-platinum (Au@Pt) nanozymes into chains on the surface of streptavidin-magnetic beads (SA-MB). The collected Au@Pt converted colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxidized TMB (oxTMB) via its Pt shell and then enhanced the Raman signal of oxTMB by its Au core. Therefore, the presence of Salmonella could be dexterously converted into cross-validated colorimetric and SERS signals, providing more reliable conclusions. Notably, dCas9-mediated secondary recognition of amplicons reduced background signal caused by nontarget amplification, and two-round signal amplification consisting of LAMP reaction and Au@Pt catalysis greatly improved the sensitivity. With this design, Salmonella as low as 1 CFU/mL could be detected within 50 min by colorimetric and SERS modes. The robustness of dCas9-CSD was further confirmed by various real samples such as lake water, cabbage, milk, orange juice, beer, and eggs. This work provides a promising point-of-need tool for pathogen detection.

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The battle against depression in the elderly is crucial due to its significant impact on their quality of life, physical and cognitive health, increased risk of social isolation and suicide, as well as the associated higher healthcare costs. This research investigates the effects of traditional and augmented reality Tai Chi, using the virtual environment "Managed Tai Chi," on depression in elderly individuals. The study involved 300 participants aged over 60 from the Beijing Medical Center, with an experimental period lasting six months and sessions held once a week. The Geriatric Depression Scale (GDS) was utilized as a diagnostic tool at the pre-test and post-test stages. The findings revealed that the VR group exhibited a more substantial reduction in depression compared to the traditional and control groups (p ≤ 0.05), indicating the enhanced efficacy of Tai Chi with VR augmentation in treating depression in the elderly.

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We evaluated the BYSL content and underlying mechanism in melanoma (SKCM) overall survival (OS). In this study, we used a comprehensive approach combining bioinformatics tools, including miRNA estimation, quantitative real-time polymerase chain reaction (qRT-PCR) of miRNAs, E3 ligase estimation, STRING analysis, TIMER analysis, examination of associated upstream modulators, protein-protein interaction (PPI) analysis, as well as retrospective and survival analyses, alongside clinical sample validation. These methods were used to investigate the content of BYSL, its methylation status, its relation to patient outcome, and its immunologic significance in tumors. Our findings revealed that BYSL expression is negatively regulated by BYSL methylation. Analysis of 468 cases of SKCM RNA sequencing samples demonstrated that enhanced BYSL expression was associated with higher tumor grade. We identified several miRNAs, namely hsa-miR-146b-3p, hsa-miR-342-3p, hsa-miR-511-5p, hsa-miR-3690, and hsa-miR-193a-5p, which showed a strong association with BYSL levels. Furthermore, we predicted the E3 ubiquitin ligase of BYSL and identified CBL, FBXW7, FZR1, KLHL3, and MARCH1 as potential modulators of BYSL. Through our investigation, we discovered that PNO1, RIOK2, TSR1, WDR3, and NOB1 proteins were strongly associated with BYSL expression. In addition, we found a close association between BYSL levels and certain immune cells, particularly dendritic cells (DCs). Notably, we observed a significant negative correlation between miR-146b-3p and BYSL mRNA expression in SKCM sera samples. Collectively, based on the previously shown evidences, BYSL can serve as a robust bioindicator of SKCM patient prognosis, and it potentially contributes to immune cell invasion in SKCM.

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The treatment, disposal, and resource utilization of waste mud are challenges for engineering construction. This study investigates the road performance of waste mud-solidified soil and explains how solidifying materials influence the strength and deformation characteristics of waste mud. Unconfined compressive strength tests, consolidated undrained triaxial shear tests, resonant column tests, and consolidation compression tests were conducted to evaluate the solidification effect. The test results show that with an increase in cement content from 5 to 9%, the unconfined compressive strength of the waste mud-solidified soil increased by over 100%, the curing time was extended from 3 to 28 days, and the unconfined compressive strength increased by approximately 70%. However, an increase in initial water content from 40 to 60% reduced the unconfined compressive strength by 50%. With the increase of cement content from 5 to 9%, the cohesion and friction angles increased by approximately 78% and 24%, respectively. The initial shear modulus under dynamic shear increased by approximately 38% and the shear strain corresponding to a damping ratio decay to 70% of the initial shear modulus decreased by nearly 11%. The compression coefficient decreased by approximately 55%. Scanning electron microscopy and X-ray diffraction tests showed that a higher cement content led to the formation of more hydration reaction products, especially an increase in the content of AlPO4, which can effectively fill the pores between soil particles, enhance the bonding between soil particles, and form a skeleton with soil particles to improve compactness. Consequently, the strength of the waste mud-solidified soil increased significantly while its compressibility decreased. This study can provide data support for dynamic characteristics of waste mud solidified soil subgrade.

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PURPOSE: The purpose of this study was to explore the expression, prognostic value and immune correlation of Cofilin 1 protein(CFL-1) in head and neck squamous cell carcinoma(HNSCC). METHODS: The expression and prognostic value of CFL-1 in head and neck squamous cell carcinoma(HNSCC) was explored in the cancer genome map database (TCGA) and gene expression total databases (GEO), and the potential immune pathway of CFL-1 in HNSCC was revealed by GESA and cibersoft analysis. The data were statistically analyzed using SPSS 26.0 software package. RESULTS: CFL-1 was significantly up-regulated in HNSCC tissue. The expression level of CFL-1 was significantly correlated with the overall survival status of HNSCC. High expression of CFL-1 was significantly associated with a lower overall survival rate. In addition, multivariate Cox survival analysis showed that CFL-1 expression was independent predictors of poor prognosis of HNSCC. GESA and cibersoft analysis showed that the imbalance of CFL-1 expression affected multiple signal pathways and infiltration of immune cells. CONCLUSIONS: CFL-1 is highly expressed in HNSCC and is significantly associated with poor prognosis of NHSCC. It is a potential prognostic marker of HNSCC.

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PURPOSE: 123I-Ioflupane SPECT is an effective tool for the diagnosis and progression assessment of Parkinson's disease (PD). Radiomics and deep learning (DL) can be used to track and analyze the underlying image texture and features to predict the Hoehn-Yahr stages (HYS) of PD. In this study, we aim to predict HYS at year 0 and year 4 after the first diagnosis with combined imaging, radiomics and DL-based features using 123I-Ioflupane SPECT images at year 0. METHODS: In this study, 161 subjects from the Parkinson's Progressive Marker Initiative database underwent baseline 3T MRI and 123I-Ioflupane SPECT, with HYS assessment at years 0 and 4 after first diagnosis. Conventional imaging features (IF) and radiomic features (RaF) for striatum uptakes were extracted from SPECT images using MRI- and SPECT-based (SPECT-V and SPECT-T) segmentations respectively. A 2D DenseNet was used to predict HYS of PD, and simultaneously generate deep features (DF). The random forest algorithm was applied to develop models based on DF, RaF, IF and combined features to predict HYS (stage 0, 1 and 2) at year 0 and (stage 0, 1 and ≥ 2) at year 4, respectively. Model predictive accuracy and receiver operating characteristic (ROC) analysis were assessed for various prediction models. RESULTS: For the diagnostic accuracy at year 0, DL (0.696) outperformed most models, except DF + IF in SPECT-V (0.704), significantly superior based on paired t-test. For year 4, accuracy of DF + RaF model in MRI-based method is the highest (0.835), significantly better than DF + IF, IF + RaF, RaF and IF models. And DL (0.820) surpassed models in both SPECT-based methods. The area under the ROC curve (AUC) highlighted DF + RaF model (0.854) in MRI-based method at year 0 and DF + RaF model (0.869) in SPECT-T method at year 4, outperforming DL models, respectively. And then, there was no significant differences between SPECT-based and MRI-based segmentation methods except for the imaging feature models. CONCLUSION: The combination of radiomic and deep features enhances the prediction accuracy of PD HYS compared to only radiomics or DL. This suggests the potential for further advancements in predictive model performance for PD HYS at year 0 and year 4 after first diagnosis using 123I-Ioflupane SPECT images at year 0, thereby facilitating early diagnosis and treatment for PD patients. No significant difference was observed in radiomics results obtained between MRI- and SPECT-based striatum segmentations for radiomic and deep features.

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Aptamers are nucleic acid sequences that specifically bind with target molecules and are vital to applications such as biosensing, drug development, disease diagnostics, etc. The traditional selection procedure of aptamers is based on the Systematic Evolution of Ligands by an Exponential Enrichment (SELEX) process, which relies on repeating cycles of screening and amplification. With the rapid development of aptamer applications, RNA and XNA aptamers draw more attention than before. But their selection is troublesome due to the necessary reverse transcription and transcription process (RNA) or low efficiency and accuracy of enzymes for amplification (XNA). In light of this, we review the recent advances in aptamer selection methods and give an outlook on future development in a non-SELEX approach, which simplifies the procedure and reduces the experimental costs. We first provide an overview of the traditional SELEX methods mostly designed for screening DNA aptamers to introduce the common tools and methods. Then a section on the current screening methods for RNA and XNA is prepared to demonstrate the efforts put into screening these aptamers and the current difficulties. We further predict that the future trend of aptamer selection lies in non-SELEX methods that do not require nucleic acid amplification. We divide non-SELEX methods into an immobilized format and non-immobilized format and discuss how high-resolution partitioning methods could facilitate the further improvement of selection efficiency and accuracy.

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The aim of the current study was to investigate the effects of ingesting different dosages of caffeine (CAF) prior to plyometric jump training (PJT) on sport-related performance and physiological parameters in male basketball players. Twenty-four young athletes were randomly divided into 3 groups and performed 6 weeks of PJT while consuming 3 mg·kg-1 of body mass caffeine (CAF3, n = 8), 6 mg·kg-1 body mass caffeine (CAF6, n = 8) or placebo (PL; n = 8) one hour prior to each training session. Before and after the 6-week PJT, the players were evaluated for field-based basketball-specific performance measures (vertical jump, 20-m sprint, Illinois change of direction speed [CODS], and maximal strength) and lab-based physiological (aerobic capacity and anaerobic power) parameters. CAF3, CAF6, and PL groups demonstrated significant improvements in vertical jump (ES = 1.07, 1.45, and 1.1, respectively), 20-m sprint (ES = - 0.50, - 0.61, and - 0.36), change of direction performance (ES = - 1.22, - 1.26, and - 1.09), maximal strength (ES = 1.68, 2.29, and 1.17), maximum oxygen uptake (V̇O2max) (ES = 1.09, 1.59, and 0.92), and peak (ES = 1.82, 1.85, and 0.82) and average power output (ES = 1.39, 1.32, and 1.07) after 6 weeks of training. Comparative analysis of individual adaptive responses to training indicated that the CAF6 led to insignificantly greater effects in vertical jump (ES = 1.45), maximal strength (ES = 2.29), and V̇O2max (ES = 1.59) with lower residuals in individual changes and lower coefficient of variations (CV) in mean group changes. Regarding sprint and CODS performance, both experimental groups indicated similar changes, residuals in individual changes, and CVs in mean group changes. Overall, consuming 6 mg·kg-1 body mass caffeine induces superior adaptations in aerobic fitness, anaerobic power, and sport-specific performance measures, with lower inter-individual variability in the adaptations and more homogenized changes over the training period.

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Breast cancer (BRCA) is one of the most common malignant tumors affecting women worldwide. DNA methylation modifications can influence oncogenic pathways and provide potential diagnostic and therapeutic targets for precision oncology. In this study, we used non-parametric permutation tests to identify differentially methylated positions (DMPs) between paired tumor and normal BRCA tissue samples from the Cancer Genome Atlas (TCGA) database. Then, we applied non-negative matrix factorization (NMF) to the DMPs to derive eight distinct DNA methylation signatures. Among them, signatures Hyper-S3 and Hypo-S4 signatures were associated with later tumor stages, while Hyper-S1 and Hypo-S3 exhibited higher methylation levels in earlier stages. Signature Hyper-S3 displayed an effect on overall survival. We further validated the four stage-associated signatures using an independent BRCA DNA methylation dataset from peripheral blood samples. Results demonstrated that 24 commonly hypomethylated sites in Hypo-S4 showed lower methylation in BRCA patients compared to healthy individuals, suggesting its potential as an early diagnostic biomarker. Furthermore, we found that methylation of 23 probes from four stage-related signatures exhibited predictive power for immune therapy response. Notably, methylation levels of all three probes from the Hypo-S4 and activity of the Hypo-S4 demonstrated highly positive relevance to PD-L1 gene expression, implying their significant predictive values for immunotherapy outcomes. GO and KEGG pathway enrichment analysis revealed that genes with these 23 immunotherapy-related methylation probes are mainly involved in glycan degradation or protein deglycosylation. These methylation signatures and probes may serve as novel epigenetic biomarkers for predicting tumor immunotherapy response. Our findings provide new insights into precision oncology approaches for BRCA.

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Ammonia (NH3), which is a precursor of secondary particulate matter (PM), can be produced through three-way catalyst (TWC) side reactions in light-duty gasoline vehicles (LDGVs), posing a threat to human health and air quality. To explore ammonia emission characteristics, 8 LDGVs and 1 hybrid electric light-duty vehicle (HEV) with various mileages traveled were analyzed with a chassis dynamometer system during regulation driving cycles. The emission factors of the adopted China VI in-use LDGVs were 7.04 ± 2.61 mg/km under cold-start conditions and 4.94 ± 1.69 mg/km under hot-start conditions. With increasing mileage traveled, the total ammonia emissions increased, and the difference between the cold/hot-start results decreased. The emissions of in-use LDGVs with bi-fuel engines were analyzed, and more ammonia was generated in the compressed natural gas (CNG) mode through the hydrocarbon (HC) reforming reaction. The relationship between the emissions of ammonia and conventional pollutants was established. During the initial cold-start phase, a delay in ammonia formation was observed, and the ammonia emissions conformed with the CO and HC emissions after exhaust heating. Vehicle specific power (VSP) analysis revealed that the interval of highest ammonia emissions corresponded to acceleration events at high speeds. For the HEV, the transition from motor to engine drive conditions contributed to ammonia emission occurrence because of the more pronounced cold-start events. The use of HEV technology could introduce additional uncertainties in controlling urban ammonia emissions. Detailed analysis of emission characteristics could provide data support for future research on ammonia emission standards and control strategies for LDGVs.

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Piezoceramic membranes have emerged as a prominent solution for membrane fouling control. However, the prevalent use of toxic lead and limitations of vibration-based anti-fouling mechanism impede their wider adoption in water treatment. This study introduces a Mn/BaTiO3 piezoceramic membrane, demonstrating a promising in-situ anti-fouling efficacy and mechanism insights. When applied to an Alternating Current at a resonant frequency of 20 V, 265 kHz, the membrane achieves optimal vibration, effectively mitigating various foulants such as high-concentration oil (2500 ppm, including real industrial oil wastewater), bacteria and different charged inorganic colloidal particles, showing advantages over other reported piezoceramic membranes. Importantly, our findings suggest that the built-in ultrasonic vibration of piezoceramic membranes can generate reactive oxygen species. This offers profound insights into the distinct anti-fouling processes for organic and inorganic wastewater, supplementing and unifying the traditional singular vibrational anti-fouling mechanism of piezoceramic membranes, and potentially propelling the development of piezoelectric catalytic membranes.