The Implementation of a MOOC-Based Flipped Classroom Teaching Method in the Context of Oncology Radiotherapy Residency Training.

The objective of this study is to examine the efficacy of the flipped classroom blended teaching method in the context of massive open online courses (MOOCs) for implementing standardized training and teaching of residents in oncology radiotherapy. A total of 48 junior residents who received standardized training at the Oncology Radiology Department of Harbin Medical University Cancer Hospital between September 2021 and August 2023 were randomly divided into two groups-i.e., the research group (24 cases) and the control group (24 cases)-using the random number table method. The control group received conventional didactic training, whereas the research group participated in a blended learning approach based on the MOOC model. The assessment results, along with the evaluations of teaching effectiveness, self-learning ability, and teaching satisfaction questionnaires, were observed and compared for the two groups of students. Compared with the control group, the research group presented significantly higher scores on theoretical foundations, skill operation, and case analysis (P < 0.05). The research group also showed greater outcomes than the control group in terms of improved theoretical knowledge, problem-solving skills, self-learning ability, teamwork, and communication (P < 0.05). The students in the research group presented significantly higher scores on measures of self-motivation beliefs, task analysis, self-monitoring and adjustment, and self-evaluation than those in the control group (P < 0.05). The research group also demonstrated significantly higher levels of satisfaction than the control group in terms of improvements in learning interest and initiative, clinical thinking ability, problem-solving ability, team cooperation ability, and the level of radiotherapy target delineation (P < 0.05). The implementation of MOOC-based flipped classroom blended teaching was shown to have positive effects on the standardized training and teaching of residents in the field of oncology radiotherapy. This approach can undoubtedly enhance students' academic performance, problem-solving abilities, and self-learning aptitudes while effectively stimulating their learning interests and initiative. Therefore, MOOC-based flipped classroom blended teaching is a valuable candidate for clinical application and promotion.

Organic-Inorganic Dual-Network Composite Separators for Lithium Metal Batteries.

The suboptimal ionic conductivity of commercial polyolefin separators exacerbates uncontrolled lithium dendrite formation, deteriorating lithium metal battery performance and posing safety hazards. To address this challenge, a novel organic-inorganic composite separator designed is prepared to enhance ion transport and effectively suppress dendrite growth. This separator features a thermally stable, highly porous poly(m-phenylene isophthalamide) (PMIA) electrospun membrane, coated with ultralong hydroxyapatite (HAP) nanowires that promote "ion flow redistribution." The synergistic effects of the nitrogen atoms in PMIA and the hydroxyl groups in HAP hinder anion transport while facilitating efficient Li+ conduction. Meanwhile, the optimized unilateral pore structure ensures uniform ion transport. These results show that the 19 µm-thick HAP/PMIA composite separator achieves remarkable ionic conductivity (0.68 mS cm-1) and a high lithium-ion transference number (0.51). Lithium symmetric cells using HAP/PMIA separators exhibit a lifespan exceeding 1000 h with low polarization, significantly outperforming commercial polypropylene separators. Furthermore, this separator enables LiFePO4||Li cells to achieve an enhanced retention of 97.3% after 200 cycles at 1 C and demonstrates impressive rate capability with a discharge capacity of 72.7 mAh g-1 at 15 C.

Smoking cessation and mortality risk reduction in older adults with long-term smoking history.

BACKGROUND: The association between smoking cessation and decreased mortality existed among former smokers has been well documented. However, evidence is limited for smokers with long-term exposure. This study aims to quantify the association between smoking cessation and mortality by years since quitting in older adults with long-term smoking history. METHODS: Data from Beijing Healthy Aging Cohort Study (BHACS), conducted among communities aged over 55 years old at recruitment, were collected via questionnaire between July 2009 and September 2015 and followed up for all-cause and cancer mortality until March 2021. Self-reported smoking status and years since quitting were collected at baseline. Cox proportional hazards models were used to examine the association between smoking cessation and all-cause and cancer mortality. RESULTS: A total of 11 235 participants (43.9% male) were included, with a mean age of 70.35 (SD 7.71) years. Former smokers comprised 31.7% of the cohort, with a median smoking duration of 43 (IQR: 34-50) years. During 71 573 person-years of follow-up, there were 1 617 deaths (14.4% of the total cohort), of which 872 (17.7%) occurred among male participants. Compared with never smokers, HR (95%CI) for participants who current smoked was 2.898 (2.092-4.013); quit smoking less than 10 years (medians [quartiles] 4 [1, 7] years) before recruitment was 2.738(1.972-3.802); 10 to 20 years (16 [13, 20] years), 1.807(1.286-2.540); and 20 years or more (30 [25, 37] years), 1.293(0.981-1.705). The risk of all-cause and cancer mortality decreased gradually over years since quitting. Quitting less than 10 years, 10 to 20 years and 20 years or more, former smokers avoided an estimated 8.4%, 57.5% and 84.6% of excess all-cause mortality associated with current smoking, respectively. The association between smoking cessation and decreased mortality was observed among former smokers regardless of smoking history. CONCLUSIONS: In this study, current smoking was associated with nearly triple the mortality risk compared to never smoking. Smoking cessation, even after a long-term smoking history, was associated with significant decreases in the relative excess mortality linked to continuing smoking. The association were more pronounced in men.

PRKAA2-mediated mitophagy regulates oxygen consumption in yak renal tubular epithelial cells under chronic hypoxia.

Hypoxic environments are significant factors in the induction of various kidney diseases and are closely associated with high oxygen consumption in the kidneys. Yaks live at high altitude for a long time, exhibit a unique ability to regulate kidney oxygen consumption, protecting them from hypoxia-induced damage. However, the mechanisms underlying the regulation of oxygen consumption in yak kidneys under hypoxic conditions remain unclear. To explore this hypoxia adaptation mechanism in yak kidneys, this study analyzed the oxygen consumption rate (OCR) of renal tubular epithelial cells (RTECs) under hypoxia. We found that the OCR and apoptosis rates of RTECs under chronic hypoxia (> 24 h) were lower than those under acute hypoxia (≤ 24 h). However, when oxygen consumption was promoted under chronic hypoxia, the apoptosis rate increased, indicating that reducing the cellular OCR is crucial for maintaining RTECs activity under hypoxia. High-throughput sequencing results showed that the mitophagy pathway is likely a key mechanism for inhibiting OCR of yak RTECs, with protein kinase AMP-activated catalytic subunit alpha 2 (PRKAA2) playing a significant role in this process. Further studies demonstrated that chronic hypoxia activates the mitophagy pathway, which inhibits oxidative phosphorylation (OXPHOS) while increasing glycolytic flux in yak RTECs. Conversely, when the mitophagy pathway was inhibited, there was an increase in the activity of OXPHOS enzymes and OCR. To further explore the role of PRKAA2 in the mitophagy pathway, we inhibited PRKAA2 expression under chronic hypoxia. Results showed that the downregulation of PRKAA2 decreased the expression of mitophagy-related proteins, such as p-FUNDC1/FUNDC1, LC3-II/LC3-I, BNIP3 and ULK1 while upregulating P62 expression. Additionally, there was an increase in the enzyme activities of Complex II, Complex IV, PDH, and SDH, which further promoted oxygen consumption in RTECs. These findings suggest that PRKAA2 mediated mitophagy under chronic hypoxia is crucial mechanism for reducing oxygen consumption in yak RTECs.

Sleep status of centenarians and its association with death in the China Hainan Centenarian Cohort Study.

OBJECTIVE: This study investigated the associations of sleep status (duration and quality) with all-cause death among centenarians, using data from the China Hainan Centenarians Cohort Study. METHOD: The epidemiological distribution of sleep duration and sleep quality (estimated using the Pittsburgh Sleep Quality Index) was described based on the data from the China Hainan Centenarians Cohort Study. Cox regression was used to analyze the association between sleep status and all-cause mortality. RESULTS: A total of 994 centenarians, with an average age of 102.77 ± 2.75years, were included. The median (Q1, Q3) daytime sleep duration was 1.00 (0.50, 1.50) hour, while nighttime sleep duration and total sleep duration were 8.00 (7.00, 9.00) hours and 9.00 (8.00, 10.50) hours, respectively. By the end of the follow-up period, 517 centenarians had died, with a median follow-up time of 4.2 (1.3-5.0) years. A noteworthy finding emerged: male centenarians with a daytime sleep duration of at least 2 hours had a 97% greater risk of all-cause mortality (HR=1.97, 95%CI: 1.07-3.62, P = .039) than those who got less daytime sleep, after adjusting for potential confounders. CONCLUSION: The sleep duration patterns of centenarians in Hainan were comparable to those in other provinces of China. Centenarians who sleep longer had a higher risk of all-cause mortality. This risk plateaued after more than 9 hours of sleep, with no gender differences observed. Furthermore, the duration of daytime sleep was significantly associated with all-cause mortality among male centenarians.

The Group Intertemporal Decision-Making Process.

Intertemporal decision making is the process by which individuals make judgments or choices regarding outcomes that occur at different times. Although intertemporal decision making is widely investigated, most studies explore it in terms of individual decision making, while neglecting group decision making, which holds more practical significance and adaptive value. This study recommends adopting a "two-process" approach that uses self-assessment questionnaires, audiovisual recordings, and visual decision-making tools to quantify interpersonal interaction processes and information processing in group intertemporal decision-making settings. In this way, studies can reveal the psychological and theoretical mechanisms of the group intertemporal decision-making process. At the level of interpersonal interaction processes, such an approach can identify the differential mechanisms between group and individual intertemporal decision making. In terms of information processing, it can reveal the mechanisms of the decision-making process in group intertemporal decision making. The findings of such work can provide a basis for interventions and nudges that encourage more visionary group intertemporal decision making.

Effects of plastic aging on biodegradation of polystyrene by Tenebrio molitor larvae: Insights into gut microbiome and bacterial metabolism.

Plastics aging reduces resistance to microbial degradation. Plastivore Tenebrio molitor rapidly biodegrades polystyrene (PS, size: < 80 µm), but the effects of aging on PS biodegradation by T. molitor remain uncharacterized. This study examined PS biodegradation over 24 days following three pre-treatments: freezing with UV exposure (PS1), UV exposure (PS2), and freezing (PS3), compared to pristine PS (PSv) microplastic. The pretreatments deteriorated PS polymers, resulting in slightly higher specific PS consumption (602.8, 586.1, 566.7, and 563.9 mg PS·100 larvae-1·d-1, respectively) and mass reduction rates (49.6 %, 49.5 %, 49.2 %, and 48.7 %, respectively) in PS1, PS2, and PS3 compared to PSv. Improved biodegradation correlated with reduced molecular weights and the formation of oxidized functional groups. Larvae fed more aged PS exhibited greater gut microbial diversity, with microbial community and metabolic pathways shaped by PS aging, as supported by co-occurrence network analysis. These findings indicated that the aging treatments enhanced PS biodegradation by only limited extent but impacted greater on gut microbiome and bacterial metabolic genes, indicating that the T. molitor host have highly predominant capability to digest PS plastics and alters gut microbiome to adapt the PS polymers fed to them.

The reduction of nitrobenzene by Fe(II)-goethite-hematite heterogeneous systems: Insight from thermodynamic parameters of reduction potential.

Determining the contaminants reduction rate by dissolved ferrous iron (Fe(II)aq) bound to iron oxides is curial for evaluating the abiotic attenuation of contaminants in aquifers. However, few studies have assessed the contaminants reduction rate controlled by thermodynamic parameters in heterogeneous systems with different iron oxides. In this study, a linear free energy relationship (LFER) was established between the nitrobenzene reduction rate and the thermodynamic driving force (reduction potential (EH) and pH) in Fe(II)aq-goethite-hematite co-existing systems. Results showed that the reduction rate of nitrobenzene correlated with the EH of the heterogeneous system. The standard reduction potential (EH0mix) of the mixed iron oxides could be obtained by a proportionate linear combination of the single iron oxide system EH0. Based on this, the EH of the heterogeneous systems could be calculated theoretically by combining EH0mix and the Nernst equation. Furthermore, a parallel LFER with the slope of 1 was established to associate the nitrobenzene reduction rate with EH and pH. The intercept term was related to the adsorption capacity of different iron oxides towards Fe(II)aq. The Fe(II)aq saturation adsorption capacity of hematite was 1.5 times higher than that of goethite. After normalizing the nitrobenzene reduction rate to the Fe(II)aq saturation adsorption capacity, the maximum difference in intercept terms was reduced from 37% to 15%. These findings would provide an important and feasible methodological support for the quantitative evaluation of abiotic attenuation of contaminants in groundwater.

Efficacy evaluation of a bivalent subunit vaccine against epidemic PEDV heterologous strains with low cross-protection.

Variant Porcine epidemic diarrhea virus (PEDV), which causes diarrhea and high mortality in piglets, has become a major pathogen, and co-epidemics of different subtypes of the virus have become a very thorny problem for the clinical prevention and control of PEDV. However, cross-protection between epidemic G2a and G2b subtype strains has not been observed, and there is currently no vaccine against both G2a and G2b strains. In this study, we demonstrate the low cross-protection between G2a and G2b strains with piglet immunization and challenge tests. The trimeric full-length S proteins of G2a and G2b variants were purified and a bivalent subunit vaccine against PEDV G2a/G2b-S was developed. In active and passive immune protection tests, the bivalent subunit vaccine produced high neutralizing antibody titers and S-specific immunoglobulin G (IgG) and IgA titers against both the G2a and G2b strains in piglets and sows. In the attack phase of the viruses, the clinical symptoms and microscopic lesions in the immunized groups were significantly alleviated. Importantly, the PEDV G2a/G2b-S bivalent subunit vaccine conferred effective passive immunity against PEDV G2a and G2b challenges in the form of colostrum-derived antibodies from the immunized sows. In conclusion, our data demonstrate the low cross-protection of PEDV epidemic G2a and G2b strains and show that the G2a/G2b-S bivalent subunit vaccine is protective against both G2a and G2b strains. It is therefore a candidate vaccine for PEDV prevention. IMPORTANCE: The detection rate of PEDV G2a subtype strains is currently increasing. Although commercial vaccines are available, most vaccines do not exert an ideal protective effect against these strains. Furthermore, there is no definitive research into the cross-protection between G2a and G2b strains, and no bivalent vaccine provides joint protection against both. Therefore, in this study, we investigated the cross-protection between PEDV G2a and G2b strains and designed a candidate bivalent subunit vaccine combining the trimeric S proteins of the G2a and G2b subtypes. We demonstrate that the cross-protection between strains G2a and G2b is poor and that this bivalent subunit vaccine protects piglets from viral attack by inducing both active and passive immunity. This study emphasizes the effectiveness of the PEDV G2a/G2b-S bivalent subunit vaccine and provides a feasible method for the development of efficient PEDV vaccines.

The optimal applications of scPDSI and SPEI in characterizing meteorological drought, agricultural drought and terrestrial water availability on a global scale.

The Palmer Drought Severity Index (scPDSI) and the Standardized Precipitation Evapotranspiration Index (SPEI) are two of the most commonly used drought indices. However, scPDSI and SPEI at a specific scale are often used interchangeably to characterize meteorological drought, agricultural drought, or terrestrial water availability, leading to potential inaccuracies in research outcomes. This study thus presents a global-scale assessment of the applications of scPDSI and SPEI at various timescales (SPEIs) in these contexts. Our findings indicate that scPDSI is more suitable for monitoring agricultural drought than meteorological drought, and highlight the effectiveness of SPEI at one month scale (SPEI01) for meteorological drought. Additionally, SPEI at nine months scale (SPEI09) is more appropriate for agricultural drought. Regarding their relationship with vegetation water stress, scPDSI and SPEI09 are more closely associated with root-zone soil moisture, while SPEI01 is most closely linked to vapor pressure deficit. Furthermore, we evaluate the capability of scPDSI and SPEI in representing terrestrial water availability by analyzing the responses of diverse vegetation indicators to them, including the Normalized Difference Vegetation Index (NDVI), Leaf Area Index (LAI), Solar-Induced Chlorophyll Fluorescence (SIF), and Gross Primary Productivity (GPP). All four vegetation indicators show the highest sensitivity of negative response to SPEI01 in cold climate regions, suggesting SPEI01 is most applicable in these regions. In drylands, vegetation indicators exhibit higher sensitivity of positive responses to SPEI at six months scale (SPEI06) and SPEI09, indicating SPEI06 and SPEI09 effectively characterize water availability in such areas. These findings enhance the understanding of scPDSI and SPEI, providing clearer guidelines for their global-scale applications in meteorological drought, agricultural drought, and terrestrial water availability.

Cockroach Blaptica dubia biodegrades polystyrene plastics: Insights for superior ability, microbiome and host genes.

The report demonstrated that a member of cockroach family, Blaptica dubia (Blattodea: Blaberidae) biodegraded commercial polystyrene (PS) plastics with Mn of 20.3 kDa and Mw of 284.9 kDa. The cockroaches digested up to 46.6 % of ingested PS within 24 h. The biodegradation was confirmed by the 13C isotopic shift of the residual PS in feces versus pristine PS (Δ Î´13C of 2.28 ‰), reduction of molecular weight and formation of oxidative functional groups in the residual PS. Further tests found that B.dubia cockroaches degraded all eight high purity PS microplastics with low to ultra-high molecular weights (MW) at 0.88, 1.20, 3.92, 9.55, 62.5, 90.9, 524.0, and 1040 kDa, respectively, with superior biodegradation ability. PS depolymerization/biodegradation pattern was MW-dependent. Ingestion of PS shifted gut microbial communities and elevated abundances of plastic-degrading bacterial genes. Genomic, transcriptomic and metabolite analyses indicated that both gut microbes and cockroach host contributed to digestive enzymatic degradation. PS plastic diet promoted a highly cooperative model of gut digestive system. Weighted gene co-expression network analysis revealed different PS degradation patterns with distinct MW profiles in B. dubia. These results have provided strong evidences of plastic-degrading ability of cockroaches or Blaberidae family and new understanding of insect and their microbe mediated biodegradation of plastics.

Deciphering the roles of attached and suspended sludges in simultaneous nitrogen and phosphorus removal in an IFAS system based on metagenomic analysis.

Integrated fixed-film activated sludge (IFAS) system, an improvement of the activated sludge process, combines the advantages of both attached sludge (AS) and suspended sludge (SS). This study aimed to fully decipher the roles of AS and SS in simultaneous N and P removal in an IFAS system through metagenomic analysis. It was found that AS contributed about 84.04%, 97%, and 95.12% to exogenous NO3--N reduction, endogenous NO3--N reduction, and endogenous NO2--N reduction, respectively. Compared with AS, SS exhibited a greater contribution to anaerobic P release (69.06%) and aerobic P uptake (73.48%). Nitrate and nitrite reductase enzymes showed higher activities in AS, while the activities of exopolyphosphatase and alkaline phosphatase D were more active in SS. P content further indicated that in AS, only a small amount of P was stored in EPS, with most presented intracellularly. In SS, the amount of P stored in EPS was found to be higher. Metagenomic analysis revealed genes related to the synthesis and degradation of endogenous carbon were higher in AS, whereas the TCA cycle exhibited higher activity in SS. P removal-related genes (such as ppk2, ppx, and adk) was significantly higher in SS than in AS. The alteration of genes associated with nitrogen metabolism suggested that the microbes in AS had a higher capacity for nitrification and denitrification. In summary, the discrepancy in the roles of AS and SS in N and P removal in IFAS can be attributed to variations in enzyme activity, P storage in EPS, microbial community composition, and functional gene abundance.

Influence of perfluorooctanoic acid on alkaline anaerobic fermentation of waste activated sludge: Perspective from volatile fatty acids production and sludge reduction.

Alkaline anaerobic fermentation is an effective approach for resource utilization and reduction of waste activated sludge (WAS). Perfluorooctanoic acid (PFOA) is widespread in WAS, however, its potential impact on alkaline anaerobic fermentation of WAS remains largely unknown. Hence, this study focused on investigating the influence of PFOA on volatile fatty acids (VFAs) production and sludge reduction during alkaline anaerobic fermentation (pH = 10 ± 0.1), as well as the critical mechanisms. Results demonstrated that low PFOA concentration (5 mg/kg-TS) raised VFAs yield to 109.37%, while high levels of PFOA (25 and 50 mg/kg-TS) remarkably decreased VFAs production to 89.55% and 80.44% of the control. Mechanism exploration revealed that PFOA facilitated the solubilization process, and low PFOA level enhanced the accumulation of VFAs via increased bioavailable substrates and the activities of enzymes and microorganisms. On the contrary, high levels of PFOA were substantial biotoxicity, inducing excessive ROS production, causing oxidative damage, and reducing enzyme activity and functional microbial abundance, thereby decreasing VFAs production. Additionally, further analysis of sludge physicochemical properties confirmed that the effect of PFOA on WAS reduction exhibited the same trend as VFAs production. This work provides a basis for PFOA environmental risk assessment and WAS resource utilization.

Variation in innate immune responses to porcine epidemic diarrhea virus infection in piglets at different ages.

Porcine epidemic diarrhea virus (PEDV) poses a significant threat to pigs, with piglets under seven days old facing a mortality rate of up to 100 %. This study aimed to explore the maturation of the immune system in piglets across different age groups and their corresponding immune responses to PEDV infection. Real-time quantitative PCR was employed to assess the relative mRNA expression of inflammation-related factors in infected pigs compared to non-infected counterparts at varying ages. Additionally, flow cytometry was utilized to analyze the relative counts of CD4+ and CD8+ T cells, as well as CD21+ B cells, in peripheral blood, spleen, mesenteric lymph nodes, and Peyer's patches of piglets at different developmental stages. Our findings revealed a notable increase in IFN-α and IFN-γ, a decrease in TNF-α, and elevated expression of IL-1ß, IL-6, IL-10, and IL-17 following PEDV infection. Furthermore, the numbers of CD4+ and CD8+ T cells, along with CD21+ B cells, exhibited a gradual rise with the advancement of piglets' age. Overall, our study underscores the progressive enhancement of piglets' resistance to PEDV infection as their immune system matures over time.

Biogeographic patterns and community assembly mechanisms of bacterial community in the upper seawater of seamounts and non-seamounts in the Eastern Indian Ocean.

Seamounts are widespread underwater topographic features in the ocean that exert an influential role in shaping the microbial biogeographic distribution. Nevertheless, research on the differences in microbial biogeographic distribution between seamount and non-seamount upper water column is still lacking, particularly in the Indian Ocean where studies are limited. In the present study, a total of 45 seawater samples were collected from the water column (5-200 m) of seamounts (HS) and non-seamounts (E87 transect) regions in the Eastern Indian Ocean (EIO) for the analysis of microbial biogeographic patterns and community assembly processes. The results indicated that bacterial community diversity did not differ significantly between the HS and E87 transect regions; however, the community composition was significantly different. Additionally, bacterial community diversity, composition, as well as structure were more affected by depth than by region. Community diversity tended to increase with depth in E87 transect region, while it tended to decrease in HS region. A distance decay analysis also demonstrated that bacterial communities were more influenced by environmental and depth distances than geographic distances. In the assembly of bacterial communities on HS and E87 transect regions, as well as at different depths, stochastic processes, particularly dispersal limitation, were found to be predominant. These findings enhance our comprehension of bacterial community characteristics in the upper seawater of seamounts and non-seamounts regions in the EIO and offer insights into the assembly processes shaping microbial communities at varying depths. IMPORTANCE: By comparing the bacterial diversity, composition, and structure in the upper seawater of seamount and non-seamount areas, we provide valuable insights into the influential role of seamounts in shaping microbial biogeography. The finding that the depth had a more significant impact on bacterial community characteristics than region underscores the importance of considering vertical stratification when examining microbial distributions. Moreover, the dominance of stochastic processes, particularly dispersal limitation, in governing community assembly across both seamount and non-seamount areas offers critical implications for the mechanisms underlying microbial biogeographic patterns in these dynamic ocean environments. This study expands the current knowledge and lays the groundwork for further investigations into the complex interactions between oceanographic features, environmental gradients, and microbial community dynamics in the Indian Ocean.

Novel machine-learning prediction tools for overall survival of patients with chondrosarcoma: Based on recursive partitioning analysis.

BACKGROUND: Chondrosarcoma (CHS), a bone malignancy, poses a significant challenge due to its heterogeneous nature and resistance to conventional treatments. There is a clear need for advanced prognostic instruments that can integrate multiple prognostic factors to deliver personalized survival predictions for individual patients. This study aimed to develop a novel prediction tool based on recursive partitioning analysis (RPA) to improve the estimation of overall survival for patients with CHS. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) database were analyzed, including demographic, clinical, and treatment details of patients diagnosed between 2000 and 2018. Using C5.0 algorithm, decision trees were created to predict survival probabilities at 12, 24, 60, and 120 months. The performance of the models was assessed through confusion scatter plot, accuracy rate, receiver operator characteristic (ROC) curve, and area under ROC curve (AUC). RESULTS: The study identified tumor histology, surgery, age, visceral (brain/liver/lung) metastasis, chemotherapy, tumor grade, and sex as critical predictors. Decision trees revealed distinct patterns for survival prediction at each time point. The models showed high accuracy (82.40%-89.09% in training group, and 82.16%-88.74% in test group) and discriminatory power (AUC: 0.806-0.894 in training group, and 0.808-0.882 in test group) in both training and testing datasets. An interactive web-based shiny APP (URL: https://yangxg1209.shinyapps.io/chondrosarcoma_survival_prediction/) was developed, simplifying the survival prediction process for clinicians. CONCLUSIONS: This study successfully employed RPA to develop a user-friendly tool for personalized survival predictions in CHS. The decision tree models demonstrated robust predictive capabilities, with the interactive application facilitating clinical decision-making. Future prospective studies are recommended to validate these findings and further refine the predictive model.

Increased neutrophil extracellular trap formation in oligoarticular, polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis: biomarkers for diagnosis and disease activity.

Objective: Neutrophil extracellular traps (NETs) are important factors in initiating and perpetuating inflammation. However, the role of NETs in different subtypes of juvenile idiopathic arthritis (JIA) has been rarely studied. Therefore, we aimed to explore the ability of JIA-derived neutrophils to release NETs and the effect of TNF-α (tumor necrosis factor-alpha) inhibitors on NET formation both in vitro and in vivo, and evaluate the associations of NET-derived products with clinical and immune-related parameters. Methods: The ability of neutrophils to release NETs and the effect of adalimumab on NET formation was assessed via in vitro stimulation and inhibition studies. Plasma NET-derived products were detected to assess the incidence of NET formation in vivo. Furthermore, flow cytometry and western blotting were used to detect NET-associated signaling components in neutrophils. Results: Compared to those derived from HCs, neutrophils derived from patients with oligoarticular-JIA, polyarticular-JIA and enthesitis-related arthritis were more prone to generate NETs spontaneously and in response to TNF-α or PMA in vitro. Excessive NET formation existed in peripheral circulation of JIA patients, and elevated plasma levels of NET-derived products (cell-free DNA and MPO-DNA complexes) could accurately distinguish JIA patients from HCs and were positively correlated with disease activity. Multiple linear regression analysis showed that erythrocyte sedimentation rate and TNF-α levels were independent variables and were positively correlated with cell-free DNA concentration. Notably, TNF-α inhibitors could effectively prevent NET formation both in vitro and in vivo. Moreover, the phosphorylation levels of NET-associated kinases in JIA-derived neutrophils were markedly increased. Conclusion: Our data suggest that NETs might play pathogenic roles and may be involved in TNF-α-mediated inflammation in JIA. Circulating NET-derived products possess potential diagnostic and disease monitoring value. Furthermore, the preliminary results related to the molecular mechanisms of NET formation in JIA patients provide a theoretical basis for NET-targeted therapy.

Generation and evaluation of Salmonella entericaserovar Choleraesuis mutant strains as a potential live-attenuated vaccine.

BACKGROUND: Salmonella entericaserovar Choleraesuis (S.C) is a swine enteric pathogen causing paratyphoid fever, enterocolitis, and septicemia in piglets. S. C is mainly transmitted through the fecal-oral route. Vaccination is an effective strategy for preventing and controlling Salmonella infection. RESULTS: Herein, we used CRISPR-Cas9 technology to knockout the virulence regulatory genes, rpoS, and slyA of S. C and constructed the ∆rpoS, ∆slyA, and ∆rpoS ∆slyA strains. The phenotypic characteristics of the mutant strains remained unchanged compared with the parental wild-type strain. In vivo study, unlike the wild-type strain, the ∆slyA and ∆rpoS ∆slyA strains alleviated splenomegaly, colon atrophy, and lower bacterial loads in the spleen, liver, ileum, and colon. These mutant strains survived in Peyer's patches (PPs) and mesenteric lymph nodes (MLN) for up to 15 days post-infection. Furthermore, the immunization of the ∆rpoS ∆slyA strain induced robust humoral and cellular immune responses. CONCLUSIONS: Consequently, vaccination with ∆rpoS ∆slyA conferred a high percentage of protection against lethal invasive Salmonella, specifically S. C, in mice. This study provided novel insights into the development of live-attenuated vaccines against the infection of S. C.

5-Hydroxymethylcytosines in circulating cell-free DNA as a diagnostic biomarker for nasopharyngeal carcinoma.

OBJECTIVE: To evaluate the diagnostic value of 5-hydroxymethylcytosines (5hmC) in circulating cell-free DNA (cfDNA) for nasopharyngeal carcinoma (NPC) and to develop a diagnostic model. METHODS: Genome-wide 5hmC profiles in cfDNA from 174 NPC patients and 146 non-cancer individuals were analyzed using the 5hmC-Seal technique. A cfDNA 5hmC-based diagnostic model to identify NPC patients was developed using least absolute shrinkage and selection operator (LASSO) logistic regression, and performance was evaluated with receiver operating characteristic (ROC) curves and confusion matrices. RESULTS: The 5hmC-Seal data from patients with NPC showed a different genome-wide distribution than non-tumor samples. Our initial analysis revealed a 12-gene-based 5hmC marker panel to be an accurate diagnostic model effectively distinguishing between NPC samples and non-cancerous samples (training set: area under curve (AUC)= 0.97 [95 % CI: 0.94-0.99]; and test set: AUC= 0.93 [95 % CI: 0.88-0.98]) superior to EBV DNA testing. The diagnostic score performed well in differentiating the non-cancer subjects from early-stage NPC (training set: AUC=0.99 [95 % CI: 0.98-1]; test set: AUC=0.98 [95 % CI: 0.95-1]), and advanced-stage NPC (training set: AUC=0.96 [95 % CI: 0.93-0.99]; test set: AUC=0.93 [95 % CI: 0.88-0.98]). Notably, in EBV-negative patients, the diagnostic scores showed excellent capacity for distinguishing EBV-negative patients with NPC from non-cancer subjects in both the training set (AUC= 0.94 [95 % CI: 0.88-1]) and test set (AUC=0.91 [95 % CI: 0.81-1]). CONCLUSION: 5hmC modifications in cfDNA are promising noninvasive biomarkers for NPC, offering high sensitivity and specificity, particularly for early-stage and EBV-negative NPC.

Analysis of Related Factors Influencing Hypertension Classification among Centenarians in Hainan, China.

Background: As a population ages, blood pressure levels gradually increase, leading to a higher incidence of hypertension and increased cardiovascular diseases risk. This study examines factors affecting hypertension grading among centenarians in the Hainan Province. Methods: Data from 2014 to 2016 were accessed from the cross-sectional database "Hypertension Levels and Epidemiological Characteristics of the Elderly and Centenarians in Hainan province of China". This study included 690 centenarians with hypertension. Hypertension grading was the dependent variable, analyzed against independent variables including demographic information (sex, age, ethnicity, education level, marital status, cohabitation, and regional distribution), lifestyle factors (smoking, alcohol consumption, and physical activity), body mass index (BMI), and comorbid conditions (diabetes and hyperlipidemia). Logistic regression models, adjusted for these factors, were used to assess the determinants of hypertension grading among the participants. Results: Multivariate regression analysis, after adjusting for other variables, revealed significant associations between BMI, low-density lipoprotein (LDL) levels, and hypertension grades. Individuals with BMI below 18.5 kg/m 2 had a 0.614-fold lower risk of developing grade III hypertension (odds ratio [OR]: 0.614, 95% confidence interval [CI]: 0.390-0.966, p = 0.0350) and a 0.586-fold lower risk for grade II hypertension (OR: 0.586, 95% CI: 0.402-0.852, p = 0.0052). Furthermore, individuals with elevated LDL levels had a 6.087-fold greater risk of progressing from grade I to grade III hypertension (OR: 6.087, 95% CI: 1.635-22.660, p = 0.0071) and a 4.356-fold greater risk of progressing from grade II to grade III hypertension (OR: 4.356, 95% CI: 1.052-18.033, p = 0.0423). Additionally, individuals of Li ethnicity had 1.823-fold greater risk of progressing from grade I to grade II hypertension compared to those of Han ethnicity (OR: 1.823, 95% CI: 1.033-3.218, p = 0.0383). Conclusions: A BMI below 18.5 kg/m 2 , elevated LDL, and ethnicity emerged the primary factors associated with hypertension grading in centenarians. To reduce the risk of hypertension, it is crucial for centenarians to maintain a healthy weight, normal LDL levels, and adopt dietary habits including a low-cholesterol and low-fat diet.