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Mutations modification enzymes including the tRNA N7-methylguanosine (m7G) methyltransferase complex component WDR4 were frequently found in patients with neural disorders, while the pathogenic mechanism and therapeutic intervention strategies are poorly explored. In this study, we revealed that patient-derived WDR4 mutation leads to temporal and cell-type-specific neural degeneration, and directly causes neural developmental disorders in mice. Mechanistically, WDR4 point mutation disrupts the interaction between WDR4 and METTL1 and accelerates METTL1 protein degradation. We further uncovered that impaired tRNA m7G modification caused by Wdr4 mutation decreases the mRNA translation of genes involved in mTOR pathway, leading to elevated endoplasmic reticulum stress markers, and increases neural cell apoptosis. Importantly, treatment with stress-attenuating drug Tauroursodeoxycholate (TUDCA) significantly decreases neural cell death and improves neural functions of the Wdr4 mutated mice. Moreover, adeno-associated virus mediated transduction of wild-type WDR4 restores METTL1 protein level and tRNA m7G modification in the mouse brain, and achieves long-lasting therapeutic effect in Wdr4 mutated mice. Most importantly, we further demonstrated that both TUDCA treatment and WDR4 restoration significantly improve the survival and functions of human iPSCs-derived neuron stem cells that harbor the patient's WDR4 mutation. Overall, our study uncovers molecular insights underlying WDR4 mutation in the pathogenesis of neural diseases and develops two promising therapeutic strategies for treatment of neural diseases caused by impaired tRNA modifications. [ABSTRACT FROM AUTHOR]

Conjugated polymers (CPs), which emit in the second near-infrared window (NIR-II, 1000–1700 nm), are used as biomaterials for NIR-II fluorescence imaging because of their adjustable photophysical properties and high optical stability. However, the fluorescence signal of conventional CPs is quenched in an aggregated state due to strong π–π stacking, which results in the closure of the radiation attenuation pathway. To solve this problem, the aggregation-induced emission effect is considered a reasonable strategy for enhancing the aggregative fluorescence of IR-II emitters. We herein report NIR-II conjugated polymers with typical AIE characteristics (αAIE > 3) by changing the side chain structure of receptor units and the conjugation degree of donors. Conjugated polymer nanoparticles (PoBVT NPs) exhibit outstanding performance in NIR-II fluorescence imaging (QY = 1.94%) and highly effective photothermal therapy (n = 45%). In vivo studies have shown that the location of tumors can be accurately obtained by NIR-II FL/NIR-II PA imaging, and there is a significant anti-tumor effect after laser irradiation. This work offers prospects for the design of multifunctional conjugated polymers for NIR-II FL/PA imaging to guide NIR-II PTT applications [ABSTRACT FROM AUTHOR]

Background: The high sensitivity of HBsAg quantitative tests has led to some challenges in the qualitative interpretation of weakly positive specimens. This study aimed to explore the clinical utility of neutralization confirmatory testing for specimens with low positive hepatitis B surface antigen (HBsAg). Methods: A retrospective analysis was conducted on outpatient and inpatient cases, from January 2021 to January 2022, at the Zhongshan City People's Hospital, Zhongshan. Confirmatory testing as well as enzyme-linked immunosorbent assay (ELISA) was applied to reanalyze 382 samples with low positive HBsAg detected by chemiluminescence microparticle immunoassay (CMIA). A retrospective analysis of hepatitis B serum markers, including eantigen, e-antibody, and core antibody patterns, was also performed. Results: When the HBsAg value ranged from 0.05 - 0.09 IU/mL, the positivity rate of the confirmatory testing was 34.5%. The HBsAg true positivity levels were all between 0.07 and 0.09. In the range of 0.10 - 0.49, the positivity rate of confirmatory testing was 96.1%. The three methods exhibited a high consistency, when testing samples with relatively high HBsAg values. A receiver operating characteristic (ROC) analysis showed that the optimal sensitivity and specificity were achieved at 0.14 IU/mL. For the HBV e-antigen-positive and negative groups, the positivity rate of confirmatory testing was 100% and 93.8%, with no statistical difference between them. Conclusions: For specimens with weakly positive, low-value HBsAg, particularly when the hepatitis B surface antigen level is less than 0.14 IU/mL, neutralization confirmatory testing can serve as a means for further confirmation. [ABSTRACT FROM AUTHOR]

Penile cancer is a rare malignant tumor of the male urinary system. The treatment benefit of standard first-line chemotherapy is not ideal for patients with locally advanced or metastatic lymph nodes. Immunotherapy has brought new treatment strategies and opportunities for patients with penile cancer. At present, clinical studies on immunotherapy for penile cancer have been reported, and the results show that it is effective but not conclusive. With the development of immunotherapy and the progress of molecular research technology, we can better screen the immunotherapy response population and explore new combination treatment regimens to evaluate the best combination regimen and obtain the optimal treatment options, which is also an important research direction for the immunotherapy of penile cancer in the future. [ABSTRACT FROM AUTHOR]

This paper is about the unique spatial arrangement of the capital (Nanjing) and imperial mausoleum (Xiaoling) in fourteenth-century China. According to Confucian principles and traditional practices, the location of tombs should be separated from the space of the living for philosophical and emotional reasons. However, this convention was challenged by the Hongwu emperor (1368–1398), founder of the Ming dynasty (1368–1644), who built his own imperial mausoleum, Xiaoling, within the confines of the capital, an unprecedented act. According to primary sources—ritual texts, gazettes, tour books, and poetry—this innovative capital–mausoleum plan suggests an extension of the pattern by which the Hongwu emperor honored his ancestors through spatial arrangements and incorporated the imperial ancestors into dynasty-building. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of the entry of biosimilars on the pricing of eight biologic products in 57 countries and regions. Methods: We utilized an interrupted time series design and IQVIA MIDAS® data to analyze the annual sales data of eight biologic products (adalimumab, bevacizumab, epoetin, etanercept, filgrastim, infliximab, pegfilgrastim, and trastuzumab) across 57 countries and regions from January 1, 2012, to December 31, 2019. We examined the immediate and long-term changes in biologics ex-manufacturer pricing following the entry of biosimilars to the market. Results: Following the entry of biosimilars, the average price per dose of biologic product was immediately reduced by $438 for trastuzumab, $112 for infliximab, and $110 for bevacizumab. The persistent effect of biosimilars' market entry led to further reductions in price per dose every year: by $49 for adalimumab, $290 for filgrastim, $21 for infliximab, and $189 for trastuzumab. Similarly, we analyzed the impact of biosimilars on four biologics' prices in the US, where the prices of three biologics significantly decreased every year, with filgrastim, pegfilgrastim, and infliximab decreasing by $955, $753, and $104, respectively. Conclusions: The introduction of biosimilars has significantly reduced the prices of biologics both globally and in the US. These findings not only demonstrate the economic benefits of increasing biosimilar utilization, but also emphasize the importance of biosimilars in controlling healthcare costs. Policies should aim to expand the availability of biosimilars to counteract the exponential growth of medical spending caused by the use of biologics. [ABSTRACT FROM AUTHOR]

Introduction: Disrupted in schizophrenia-1 (DISC1) is a scaffolding protein whose mutated form has been linked to schizophrenia, bipolar affective disorders, and recurrent major depression. DISC1 regulates multiple signaling pathways involved in neurite outgrowth and cortical development and binds directly to glycogen synthase kinase-3β (GSK-3β). Since ketamine activates GSK-3β, we examined the impact of ketamine on DISC1 and GSK-3β expression. Methods: Postnatal day 7 rat pups were treated with ketamine with and without the non-specific GSK-3β antagonist, lithium. Cleaved-caspase-3, GSK-3β and DISC1 levels were measured by immunoblots and DISC1 co-localization in neurons by immunofluorescence. Binding of DISC1 to GSK-3β was determined by co-immunoprecipitation. Neurite outgrowth was determined by measuring dendrite and axon length in primary neuronal cell cultures treated with ketamine and lithium. Results: Ketamine decreased DISC1 in a dose and time-dependent manner. This corresponded to decreases in phosphorylated GSK-3β, which implicates increased GSK-3β activity. Lithium significantly attenuated ketamine-induced decrease in DISC1 levels. Ketamine decreased co-immunoprecipitation of DISC1 with GSK-3β and axonal length. Conclusion: These findings confirmed that acute administration of ketamine decreases in DISC1 levels and axonal growth. Lithium reversed this effect. This interaction provides a link between DISC1 and ketamine-induced neurodegeneration. [ABSTRACT FROM AUTHOR]

Adopting Gilles Deleuze and Felix Guattari's formulations of the rhizome, this article will examine a dynamic that lies between the film Japón's (Carlos Reygadas, 2002) vernacular specificities, European modernist aesthetics and cosmopolitan spectatorship. The article aims to reveal that Japón, along with other contemporary slow films from around the world, has the potential to reify a deterritorialising and reterritorialising encounter that rethinks a Eurocentric genealogical reading of world cinema and challenges a capitalist code of filmmaking. [ABSTRACT FROM AUTHOR]

Liquid hydrogen storage and transportation is an effective method for large-scale transportation and utilization of hydrogen energy. Revealing the flow mechanism of cryogenic working fluid is the key to optimize heat exchanger structure and hydrogen liquefaction process (LH2). The methods of cryogenic visualization experiment, theoretical analysis and numerical simulation are conducted to study the falling film flow characteristics with the effect of co-current gas flow in LH2 spiral wound heat exchanger. The results show that the flow rate of mixed refrigerant has a great influence on liquid film spreading process, falling film flow pattern and heat transfer performance. The liquid film of LH2 mixed refrigerant with column flow pattern can not uniformly and completely cover the tube wall surface. As liquid flow rate increases, the falling film flow pattern evolves into sheet-column flow and sheet flow, and liquid film completely covers the surface of tube wall. With the increase of shear effect of gas-phase mixed refrigerant in the same direction, the liquid film gradually becomes unstable, and the flow pattern eventually evolves into a mist flow. [ABSTRACT FROM AUTHOR]

This study assessed second-line therapy options for metastatic non-clear cell renal cell carcinoma (nccRCC) patients following first-line tyrosine kinase inhibitor (TKI) treatment. Among 65 patients, combination therapy (TKI plus anti-PD1) showed improved response rates (ORR 50.0%, DCR 70.5%) compared to TKI monotherapy (ORR 14.3%, DCR 28.6%). Median progression-free survival (PFS) for combination therapy was 9.2 months vs. 5.4 months for TKI monotherapy, with similar adverse event rates. Anti-PD-1 plus TKI therapy appears effective and safe for nccRCC patients who progressed after initial TKI treatment. Objectives: Guidelines recommend clinical trials or tyrosine kinase inhibitor (TKI) as the first-line option for systemic therapy for non-clear cell renal cell carcinoma (nccRCC) with limited efficacy. However, the preferred subsequent options remain unclear when patients progress after first-line treatment. This study aimed to evaluate the efficacy and safety of anti-PD-1 plus TKI therapy as the second-line regimen in nccRCC. Patients and Methods: We conducted a retrospective analysis of patients with metastatic nccRCC who failed first-line TKI therapy between October 2011 and September 2020. The baseline characteristics of the patients and adverse events (AEs) were collected. Efficacy measures included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Results: The current study enrolled 65 patients, with a median age of 48 (interquartile 37-60) years. Among all patients, 21 received TKI monotherapy while 44 patients received combination therapy (TKI plus anti-PD1). The ORR and DCR for the whole cohort were 38.5% and 56.9%, respectively. ORR (50.0% vs. 14.3%, P = .006) and DCR (70.5% vs. 28.6%, P = .001) were improved in the combination group compared with the TKI group. The overall second-line PFS was 7.7 (95% CI: 6.1-9.3) months and OS was 25.2 (19.5-30.8) months. Patients receiving combination therapy had a longer PFS compared with those receiving TKI monotherapy [median PFS (95% CI): 9.2 (5.9-12.4) vs. 5.4 (2.6-8.2) m, Log-rank P = .002]. The incidence of treatment-related AEs of grade 3 or higher was comparable between the 2 groups (56.8% vs. 52.4%). Conclusion: Anti-PD-1 plus TKI therapy appeared effective and safe in the treatment of patients with metastatic nccRCC who progressed after first-line TKIs. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: Accumulating evidence has supported that mild elevated total bilirubin exerts antioxidant and anti-inflammatory properties in multiple metabolic diseases. We aimed to explore the association of circulating total bilirubin concentration with non-alcoholic fatty liver disease (NAFLD) risk and allcause mortality and examine the potential nonlinear relationships between them. Material and Methods: We used nationally representative data from the National Health and Nutrition Examination Survey (NHANES). NAFLD was assessed using the fatty liver index (FLI) and United States fatty liver index (USFLI), respectively. Results: A total of 35 912 and 17 329 participants were included in FLI-NAFLD (case with NAFLD was diagnosed by FLI) and USFLI-NAFLD (case with NAFLD was diagnosed by USFLI) groups, respectively. The mean age of total population was 46.25 years, and 48.51% were male. Compared to participants with lowest quintile of total bilirubin concentration, those with highest quintile had lower risk of NAFLD in both FLI-NAFLD (OR: 0.48, 95% CI: 0.40, 0.59) and USFLI-NAFLD (OR: 0.55, 95% CI: 0.43, 0.70) groups. Compared to participants with lowest quintile of total bilirubin concentration, the association between total bilirubin concentration and all-cause mortality was not significant among those with highest quintile of total bilirubin concentration (HR: 0.89, 95% CI: 0.66, 1.20). The restricted spline curves showed the nonlinear U-shaped association of total bilirubin concentration with NAFLD risk and all-cause mortality. The segmented linear regression analysis showed negative associations between total bilirubin concentration and risk of NAFLD in both FLI-NAFLD (OR: 0.94, 95% CI: 0.93, 0.95) and USFLI-NAFLD (OR: 0.95, 95% CI: 0.93, 0.96) groups when total bilirubin concentration was below the turning point (FLI-NAFLD: 18.81 mmol/L; USFLI-NAFLD: 15.39 mmol/L) and these associations were not significant when total bilirubin concentration was higher than the turning point. Furthermore, all-cause mortality decreased (OR: 0.97, 95%CI: 0.95, 1.00) with increased total bilirubin concentration up to the turning point (11.97 mmol/L), and then all-cause mortality increased with increasing total bilirubin concentration (OR: 1.03, 95%CI: 1.02, 1.04). Conclusions: We found that higher circulating total bilirubin concentration within the physiological range was associated with decreased risk of NAFLD and all-cause mortality among NAFLD patients. [ABSTRACT FROM AUTHOR]

In recent years, digital twin technology has developed rapidly, which has great advantages in improving production quality and saving production costs. Therefore, it is of great significance to apply digital twin technology to the spinning field to realize the prediction of spinning production quality. This study takes the carding process in yarn manufacturing as an example. First, a prediction model framework for carding process production quality is proposed based on the digital twin modeling mechanism. Each key component's modeling principles and methods are analyzed, and the modeling process and coupling between models are clarified. Next, the carding process production quality prediction model is established based on the proposed modeling framework and actual working conditions. Then, a set of comparative experiments on a generative adversarial network and a set of comparative experiments between different prediction models were designed. The results showed that the production quality prediction model of the carding process established according to the modeling method proposed in this paper meets the requirements of spinning production quality prediction, and the average error rate of the model was 5.7%. Finally, the modeling method and experimental results are discussed, and future research directions are considered. The paper has great significance for further research on quality prediction of yarn manufacturing, providing a reference for applying digital twin technology and promoting intelligent manufacturing in the spinning field. [ABSTRACT FROM AUTHOR]

As large numbers of people are suffering from gout, an accurate, rapid, and sensitive method for the detection of gout biomarker, uric acid, is important for its effective control, diagnosis, and therapy. Although colorimetric detection methods based on uricase have been considered, they still have limitations as they produce toxic H2O2 and are expensive and not stable. Here, a novel uricase‐free colorimetric method was developed for the sensitive and selective detection of uric acid based on the light‐induced oxidase‐mimicking activity of a new photosensitized covalent organic framework (COF) (2,4,6‐trimethylpyridine‐3,5‐dicarbonitrile–4‐[2‐(4‐formylphenyl)ethynyl]benzaldehyde COF [DCTP–EDA COF]). DCTP–EDA COF has a strong ability to harvest visible light, and it could catalyze the oxidation of 1,4‐dioxane, 3,3′,5,5′‐tetramethylbenzidine under visible light irradiation to produce obvious color changes. With the addition of uric acid, however, the significant inhibition of the oxidase‐mimicking activity of DCTP–EDA COF remarkably faded the color, and thus uric acid could be colorimetrically detected in the range of 2.0–150 μM with a limit of detection of 0.62 μM (3σ/K). Moreover, the present colorimetric method exhibited high selectivity; uric acid level in serum samples was successfully determined, and the recoveries ranged from 96.5% to 105.64%, suggesting the high accuracy of the present colorimetric method, which demonstrates great promise in clinical analysis. [ABSTRACT FROM AUTHOR]

As one of the important forces promoting the development of the marine economy, the marine biomedical industry (MBI) shows typical knowledge and technology-intensive characteristics. It is of great significance to explore the industrial innovation dynamic mechanism for breaking through the bottleneck of innovative development as well as achieving high-quality development. This paper constructed a system dynamics model for scientific and technological innovation (STI) in the MBI and then explored the dynamic mechanism of STI in the industry through simulation. The study found that, in the innovation environment subsystem, the two factors of the intellectual property protection intensity and the government's scientific research funding input had the most significant positive driving effects on STI of the MBI; the promotion of government education funding input showed a significant strengthening trend over time, while the marine environmental regulation intensity had comparatively little effect on the level of STI. In the subsystem of innovation input, both innovation funding input and innovation personnel input were the direct driving forces for the improvement of the STI level. And enterprises played a dominant role in STI because the STI level of the MBI was more sensitive to the changes in enterprise innovation input. Compared with the individual factor input, the synergistic promotion effect of multiple factors is more significant. In addition, it was found that there was a low conversion rate of scientific research achievements in China's MBI by analyzing the influence of various factors changing on technological output and economic output. Based on the research results, this paper puts forward corresponding policy suggestions in order to provide theoretical support and a practical basis for promoting the technological innovation level of China's MBI as well as references for other countries. [ABSTRACT FROM AUTHOR]

As one of the important forces promoting the development of the marine economy, the marine biomedical industry (MBI) shows typical knowledge and technology-intensive characteristics. It is of great significance to explore the industrial innovation dynamic mechanism for breaking through the bottleneck of innovative development as well as achieving high-quality development. This paper constructed a system dynamics model for scientific and technological innovation (STI) in the MBI and then explored the dynamic mechanism of STI in the industry through simulation. The study found that, in the innovation environment subsystem, the two factors of the intellectual property protection intensity and the government's scientific research funding input had the most significant positive driving effects on STI of the MBI; the promotion of government education funding input showed a significant strengthening trend over time, while the marine environmental regulation intensity had comparatively little effect on the level of STI. In the subsystem of innovation input, both innovation funding input and innovation personnel input were the direct driving forces for the improvement of the STI level. And enterprises played a dominant role in STI because the STI level of the MBI was more sensitive to the changes in enterprise innovation input. Compared with the individual factor input, the synergistic promotion effect of multiple factors is more significant. In addition, it was found that there was a low conversion rate of scientific research achievements in China's MBI by analyzing the influence of various factors changing on technological output and economic output. Based on the research results, this paper puts forward corresponding policy suggestions in order to provide theoretical support and a practical basis for promoting the technological innovation level of China's MBI as well as references for other countries. [ABSTRACT FROM AUTHOR]

Background: Theories propose that brief, mobile, self-guided mindfulness ecological momentary interventions (MEMIs) could enhance emotion regulation (ER) and self-compassion. Such changes are posited to be mechanisms of change. However, rigorous tests of these theories have not been conducted. Objective: In this assessor-blinded, parallel-group randomized controlled trial, we aimed to test these theories in social anxiety disorder (SAD). Methods: Participants with SAD (defined as having a prerandomization cut-off score ≥20 on the Social Phobia Inventory self-report) were randomized to a 14-day fully self-guided MEMI (96/191, 50.3%) or self-monitoring app (95/191, 49.7%) arm. They completed web-based self-reports of 6 clinical outcome measures at prerandomization, 15-day postintervention (administered the day after the intervention ended), and 1-month follow-up time points. ER and self-compassion were assessed at preintervention and 7-day midintervention time points. Multilevel modeling determined the efficacy of MEMI on ER and self-compassion domains from pretrial to midintervention time points. Bootstrapped parallel multilevel mediation analysis examined the mediating role of pretrial to midintervention ER and self-compassion domains on the efficacy of MEMI on 6 clinical outcomes. Results: Participants demonstrated strong compliance, with 78% (149/191) engaging in at least 80% of the MEMI and self-monitoring prompts. MEMI was more efficacious than the self-monitoring app in decreasing ER goal--directed behavior difficulties (between-group Cohen d=-0.24) and lack of emotional clarity (Cohen d=0.16) and increasing self-compassion social connectedness (Cohen d=0.19), nonidentification with emotions (Cohen d=0.16), and self-kindness (Cohen d=0.19) from pretrial to midintervention time points. The within-group effect sizes from pretrial to midintervention were larger in the MEMI arm than in the self-monitoring app arm (ER goal--directed behavior difficulties: Cohen d=-0.73 vs -0.29, lack of emotional clarity: Cohen d=-0.39 vs -0.21, self-compassion domains of social connectedness: Cohen d=0.45 vs 0.19, nonidentification with emotions: Cohen d=0.63 vs 0.48, and self-kindness: Cohen d=0.36 vs 0.10). Self-monitoring, but not MEMI, alleviated ER emotional awareness issues (between-group Cohen d=0.11 and within-group: Cohen d=-0.29 vs -0.13) and reduced self-compassion acknowledging shared human struggles (between-group Cohen d=0.26 and within-group: Cohen d=-0.23 vs 0.13). No ER and self-compassion domains were mediators of the effect of MEMI on SAD symptoms (P=.07-<.99), generalized anxiety symptoms (P=.16-.98), depression severity (P=.20-.94), repetitive negative thinking (P=.12-.96), and trait mindfulness (P=.18-.99) from pretrial to postintervention time points. Similar nonsignificant mediation effects emerged for all of these clinical outcomes from pretrial to 1-month follow-up time points (P=.11-.98). Conclusions: Brief, fully self-guided, mobile MEMIs efficaciously increased specific self-compassion domains and decreased ER difficulties associated with goal pursuit and clarity of emotions from pretrial to midintervention time points. Higher-intensity MEMIs may be required to pinpoint the specific change mechanisms in ER and self-compassion domains of SAD. [ABSTRACT FROM AUTHOR]

Background: Artificial intelligence (AI) has been the subject of studies in autism spectrum disorder (ASD) and may affect its identification, diagnosis, intervention, and other medical practices in the future. Although previous studies have used bibliometric techniques to analyze and investigate AI, there has been little research on the adoption of AI in ASD. This study aimed to explore the broad applications and research frontiers of AI used in ASD. Methods: Citation data were retrieved from the Web of Science Core Collection (WoSCC) database to assess the extent to which AI is used in ASD. CiteSpace.5.8. R3 and VOSviewer, two online tools for literature metrology analysis, were used to analyze the data. Results: A total of 776 publications from 291 countries and regions were analyzed; of these, 256 publications were from the United States and 173 publications were from China, and England had the largest centrality of 0.33; Stanford University had the highest H-index of 17; and the largest cluster label of co-cited references was machine learning. In addition, keywords with a high number of occurrences in this field were autism spectrum disorder (295), children (255), classification (156) and diagnosis (77). The burst keywords from 2021 to 2023 were infants and feature selection, and from 2022 to 2023, the burst keyword was corpus callosum. Conclusion: This research provides a systematic analysis of the literature concerning AI used in ASD, presenting an overall demonstration in this field. In this area, the United States and China have the largest number of publications, England has the greatest influence, and Stanford University is the most influential. In addition, the research on AI used in ASD mostly focuses on classification and diagnosis, and "infants, feature selection, and corpus callosum are at the forefront, providing directions for future research. However, the use of AI technologies to identify ASD will require further research. [ABSTRACT FROM AUTHOR]

Background: We assessed nofazinlimab, an anti-PD-1 antibody, in solid tumors and combined with regorafenib in metastatic colorectal cancer (mCRC). Methods: This phase 1 study comprised nofazinlimab dose escalation (phase 1a) and expansion (phase 1b), and regorafenib dose escalation (80 or 120 mg QD, days 1–21 of 28-day cycles) combined with 300-mg nofazinlimab Q4W (part 2a) to determine safety, efficacy, and RP2D. Results: In phase 1a (N = 21), no dose-limiting toxicity occurred from 1 to 10 mg/kg Q3W, with 200 mg Q3W determined as the monotherapy RP2D. In phase 1b (N = 87), 400-mg Q6W and 200-mg Q3W regimens were found comparable. In part 2a (N = 14), both regimens were deemed plausible RP2Ds. Fatigue was the most frequent treatment-emergent adverse event (AE) in this study. Any-grade and grade 3/4 nofazinlimab-related AEs were 71.4% and 14.3%, 56.3% and 5.7%, and 57.1% and 21.4% in phases 1a, 1b, and part 2a, respectively. ORRs were 14.3% and 25.3% in phases 1a and 1b, respectively. In part 2a, no patients had radiological responses. Conclusions: Nofazinlimab monotherapy was well tolerated and demonstrated preliminary anti-tumor activity in multiple tumor types. Regorafenib plus nofazinlimab had a manageable safety profile but was not associated with any response in mCRC. Clinical trial registr ation: Clinicaltrials.gov (NCT03475251). [ABSTRACT FROM AUTHOR]

The significant impact of high levels of green finance penetration on the development of the sports industry is evident, contributing to its comprehensive and high-quality growth across multiple dimensions. After analyzing the current state of the sports industry in China, data from 31 provincial-level administrative regions between 2008 and 2021 were carefully selected. An evaluation index system was established to assess the development of green finance and the high-quality development of the sports industry. The entropy method was applied to measure the levels of green finance and the quality of sports industry development in different regions. Empirical research demonstrates a statistically significant and positive relationship between green finance and the highquality development of the sports industry, reaching a significance level of 1%. Nonetheless, there are still several challenges and areas for improvement within the realm of green finance and the sports industry's high-quality development. To propel the sports industry's growth under the umbrella of green finance, efforts should be focused on expediting the enhancement and construction of green finance, utilizing it effectively to empower the sports industry, staying attuned to the trends and dynamics of green finance development, as well as fostering a congenial environment for its further advancement. [ABSTRACT FROM AUTHOR]

A total of 271 penile squamous cell carcinoma patients (PSCC) without distant metastasis were enrolled in this study. Inflammatory biomarkers were associated with the prognostic of PSCC patients. A nomogram based on inflammation biomarkers to predict the overall survival of PSCC patients was constructed with superior predictive ability and high clinical use. The nomogram based on the inflammation biomarkers may serve as a tool in predicting the survival of PSCC patients. Background: To investigate the value of the presurgical inflammatory biomarkers including C-reactive protein (CRP), albumin (ALB), C-reactive protein to albumin ratio (CAR), Glasgow prognostic score (GPS), the modified GPS (mGPS), and the high-sensitivity modified GPS (Hs-mGPS) in penile squamous cell carcinoma (PSCC) without distant metastasis and develop a tool to predict the overall survival (OS) of PSCC patients. Methods: We retrospectively enrolled 271 PSCC patients without distant metastasis from 2006 to 2021. Patients were divided into 2 cohorts by a 7:3 ratio--a training cohort (n = 191) and a validation cohort (n = 80). We performed cox regression analyses on the training cohort and constructed a nomogram to predict OS over 1, 3, and 5 years. Data from the validation cohort was used to validate the nomogram's predictive power. Results: According to Kaplan-Meier analysis, elevated CRP (P < .001), hypoalbuminemia (P = .008), higher CAR (P < .001), higher GPS score (P < .001), higher mGPS score (P < .001), and higher Hs-mGPS score (P = .015) were associated with a decreased overall survival. GPS score, along with age, pathology N stage, and grade, was found to be an independent risk factor for poor prognosis in the multivariate analysis. We constructed a nomogram based on the prespecified variables predicting 1-, 3- and 5-year OS. The C-indexes of the nomogram in the training and validation cohorts were 0.871 and 0.869, respectively. The decision curve analysis showed that the nomogram had a larger net benefit. The Kaplan-Meier curves showed significant differences between the risk groups categorized according to the nomogram (P < .001). Conclusions: Inflammation biomarkers of systemic inflammation and nutritional status play an important role in individual OS predictions for PSCC patients without distant monitoring. The establishment of the nomogram provided a tool to predict the survival of 1-, 3-, and 5-year OS in PSCC patients without distant metastasis. [ABSTRACT FROM AUTHOR]

Background: Exclusive breastfeeding (EBF) in the first 6 weeks postpartum is key to continued breastfeeding. This study aimed to explore the role of EBF-related predictors (particularly breastfeeding intention) in breastfeeding behavior among preterm mothers at week 6 postpartum based on the theory of planned behavior (TPB). Methods: A total of 352 mothers of preterm infants were recruited, 340 of whom participated in this study. Prior to discharge, participants completed the Chinese versions of the modified Breastfeeding Attrition Predictive Tool, the Breastfeeding Knowledge Questionnaire (BKQ), the Infant Feeding Intention, and the Edinburgh Postnatal Depression Scale. Responses to the items of the Breastfeeding Behavioral Questionnaire (BBQ) were also collected by telephone at week 6 postpartum. The final analyses included 321 participants who completed the full two-wave data collection. Results: The fitness indices of the modified TPB model were acceptable. Breastfeeding knowledge and EBF before discharge positively impacted breastfeeding intention, whereas depression had a negative impact. Before discharge, breastfeeding intention fully mediated the impacts of breastfeeding attitude, social and professional support, knowledge, depression, and EBF on breastfeeding behavior and partially mediated the influence of perceived breastfeeding control on breastfeeding behavior. Conclusion: These findings indicate that TPB accurately predicts breastfeeding behavior among preterm mothers at week 6 postpartum, and breastfeeding intention is key to the above-mentioned EBF-related factors and breastfeeding behavior. The findings underline the need for further longitudinal studies and corresponding interventions for preterm mothers with a high risk of EBF attrition. [ABSTRACT FROM AUTHOR]

Background: Male breast cancer (MBC) is a rare disease, accounting for <1% of all male carcinomas. Lack of prospective data, the current therapy for MBC is based on retrospective analysis or information that is extrapolated from studies of female patients. We constructed a nomogram model for predicting the overall survival (OS) of MBC patients and verify its feasibility using data from China. Methods: Constructed a predictive model using 1224 MBC patients from the Surveillance, Epidemiology and End Results (SEER) registry between 2010 and 2015. The performance of the model was externally validated between 2002 to 2021 using 44 MBC patients from the Fujian Medical University Union Hospital. The independent prognostic factors were selected by univariate and multivariate Cox regression analyses. The nomogram was constructed to predict individual survival outcomes for MBC patients. The discriminative power, calibration, and clinical effectiveness of the nomogram were evaluated by the receiver operating characteristic (ROC) curve, and the decision curve analysis (DCA). Results: A total of 1224 male breast cancer patients were in the training cohort and 44 in the validation cohort. T status (p<0.001), age at diagnosis (p<0.001), histologic grade (p=0.008), M status (p<0.001), ER status (p=0.001), Her2 status (p=0.019), chemotherapy (p=0.015) were independently associated with OS. The diagnostic performance of this model was evaluated and validated using ROC curves on the training and validation datasets. In the training cohort, the nomogram-predicted AUC value was 0.786 for 3-year OS and 0.767 for 5-year OS. In the validation cohort, the nomogram-predicted AUC value was 0.893 for 3-year OS and 0.895 for 5-year OS. Decision curve analysis demonstrated that the nomogram was more benefit than the AJCC stage. Conclusions: We developed a nomogram that predicts 3-year and 5-year survival in MBC patients. Validation using bootstrap sampling revealed optimal discrimination and calibration, suggesting that the nomogram may have clinical utility. The results remain reproducible in the validation cohort which included Chinese data. The model was superior to the AJCC stage system as shown in the decision curve analysis (DCA). [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) joint inflammation severely affects joint function and quality of life in patients and leads to joint deformities and limb disability. The non-steroidal anti-inflammatory drugs used in the treatment of RA do not fully control the progression of joint inflammation and bone destruction and have notable adverse reactions. Traditional Chinese medicine formula JuanBiQiangGu Granules (JBQG) are commonly used for the treatment of RA inflammation and delay of bone destruction, but has not been evaluated through high-quality clinical studies. There is a pressing need for well-designed, randomized, parallel, controlled clinical studies to evaluate the exact effect of JBQG on RA joint inflammation and improvement of patient quality of life. Methods: This is a randomized, parallel, controlled clinical study in which 144 patients with rheumatoid arthritis who met the inclusion criteria were randomly assigned to 2 groups in a 1:1 ratio. The JBQG group received methotrexate 7.5mg qw and JBQG granules 8mg tid, while theMTX group receivedmethotrexate 7.5mg qw. The endpoint was 12weeks after treatment. Relevant indices at baseline, 4weeks, 8 weeks, and 12weeks after treatment were observed and recorded, and DAS28-ESR, HAQ-DI, and Sharp scores were recorded for each patient. Blood samples were collected to test forCRP, ESR, TNF-α, IL-1β, IL-6, IL-17, and INF-γ, and adverse reactions and liver and kidney function (AST, ALT, Cr, BUN)were recorded for safety assessment. After 12weeks of treatment, the effect of JBQG granules on disease activity, improvement in bone damage, and patient quality of life scores and safety in RA patients were evaluated. Results: A total of 144 subjects completed treatment (71 in the JBQG group and 73 in the MTX group) and were included in the analysis. At baseline, there were no significant differences between the groups in terms of the observed indicators (p > 0.05). After treatment, 76.06% of patients in the JBQG group had DAS28-ESR Results: A total of 144 subjects completed treatment (71 in the JBQG group and 73 in the MTX group) and were included in the analysis. At baseline, there were no significant differences between the groups in terms of the observed indicators (p > 0.05). After treatment, 76.06% of patients in the JBQG group had DAS28-ESR levels below or equal to Low, including 45.07% in Remission and 5.63% in High, compared to 53.1% in theMTX group below or equal to Low, 12.33% in Remission, and 17.81% in High. CRP was significantly reduced (8.54 ± 5.87 vs. 11.86 ± 7.92, p < 0.05, p = 0.005), ESR was significantly reduced (15.1 ± 6.11 vs. 21.96 ± 9.19, p < 0.0001), TNF-a was significantly reduced (1.44 ± 0.83 vs. 1.85 ± 1.07, p < 0.05, p = 0.011), IL-17 was significantly reduced (0.53 ± 0.33 vs. 0.71 ± 0.38, p < 0.05, p = 0.004), and INF-γ was significantly reduced (3.2 ± 1.51 vs. 3.89 ± 1.77, p < 0.05, p = 0.014). The median (IQR) OPG in the JBQG group was 2.54 (2.21-3.01), significantly higher than in the MTX group 2.06 (1.81-2.32), p < 0.0001), and the median (IQR) β-CTX in the JBQG group was 0.4 (0.32-0.43), significantly lower than in the MTX group 0.55 (0.47-0.67), p < 0.0001). The median (IQR) VSA scores were 2 (1-3), a decrease from3 (2-4) in theMTX group (p < 0.0001). The median (IQR) Sharp scores were 1 (1-2), a decrease from 2 (1-2) in the MTX group, but the difference was not statistically significant (p > 0.05, p = 0.28). The median (IQR) HAQ-DI scores were 11 (8-16), significantly lower than in the MTX group 26 (16-30) (p < 0.0001). The median (IQR) AST in the JBQG group was 16 (12-20), with a significant difference compared to the MTX group 19 (13-25) (p < 0.01, p=0.004); themedian (IQR) ALT in the JBQGgroupwas 14 (10-18), with a significant difference compared to the MTX group 16 (11-22.5) (p < 0.05, p = 0.015). There were no statistically significant differences in Cr or BUN (p > 0.05). Conclusion: JuanBiQiangGu Granules can be used to treat patients with rheumatoid arthritis, alleviate joint inflammation, reduce the incidence of adverse reactions to methotrexate, and has good safety. [ABSTRACT FROM AUTHOR]

Polymer flooding has been witnessed an effective technology for enhancing oil recovery from medium-to low-permeability reservoirs; however, direct visualization of polymer solution flow in such reservoir condition is still lacking. In this work, a three-dimensional (3D) core-on-a-chip device with a permeability of around 200 mD was prepared and employed to visualize the pore-scale flow and displacement of a self-adaptive polymer (SAP, 8.7 × 106 g$mol-1)-whose microscopic association structure and macroscopic viscosity can reversibly change in response to shear action-versus partially hydrolyzed polyacrylamide (HPAM), by recording their flow curves, monitoring dynamic transportation process via particle imaging velocimetry, and building 3D structure of remaining oil. The results show that, in singlephase flow, all polymer solutions exhibit flow thinning and then thickening regions as flow rate increases, but the transition between two regimes occurs at a small Weissenberg number (10-3-10-1) in this medium-permeable condition. In contrast to HPAM-1 with close weight-average molecular weight (Mw), the adaptive character not only extends SAP's shear-govern region, allowing SAP to propagate piece by piece and achieve higher accessible pore volume, but it also enhances the elastic resistibility of polymer in the extension-dominated regime, increasing the microscopic displacement efficiency. These two effects result in 1.5e3 times more oil recovery factor for SAP than for HPAM-1. Regarding ultra-high-Mw HPAM-2 (25 × 106 g.mol-1), plugging and chain degradation do occur, thus producing lower oil recovery than SAP. This work provides a direct approach for in-situ assessment of polymer-based displacing system under a more authentic condition of practical reservoirs. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC), although being a potentially avoidable disease, is the second most often diagnose gynecological cancer, with at minimum 530,000 new instant reported each year, and optimism for CC remains poor. Nearly half of individuals with locally advanced cervical cancer have a poor pathological response to standard therapy. As a result, research into the molecular pathogenesis of cervical cancer and associated therapeutic targets is a must. MicroRNAs (miRNAs) are possible biomarkers in cervical cancer; elevations or reductions in many distinct miRNAs discovered in individuals with this illness indicate that miRNA could contain a function to play in the illness's pathogenesis. Nevertheless, little is known about their significance in detecting individuals who do not respond to traditional therapy. As a consequence, the intention of this study is to look at the relationship among the synthesis of miRNAs (miR 217 and miR-140-3p), which can be utilized as molecular biomarkers to predict pathological responses in cervical cancer patients after radiation and chemotherapy. Various analytical techniques were used to analyze the data, including quantitative real-time PCR (qRT-PCR), growth and apoptosis analysis, western blot analysis, luciferase reporter gene analysis, immunohistochemistry, and statistical analysis. The results show that such miRNAs participate a crucial responsibility in CC cell proliferation inhibition. They might be a new therapeutic target for microRNA-mediated cell proliferation inhibition in cervical cancer. [ABSTRACT FROM AUTHOR]

Background: Metaplastic breast cancer (MBC) is a rare breast tumor and the prognostic factors for survival in patients still remain controversial. This study aims to develop and validate a nomogram to predict the overall survival (OS) of patients with MBC. Methods: We searched the Surveillance, Epidemiology, and End Results (SEER) database for data about patients including metaplastic breast cancer and infiltrating ductal carcinoma (IDC) from 2010 to 2018. The survival outcomes of patients between MBC and IDC were analyzed and compared with the Kaplan-Meier (KM) method. MBC patients were randomly allocated to the training set and validation I set by a ratio of eight to two. Meanwhile, the performance of this model was validated again by the validation II set, which consisted of MBC patients from the Union Hospital of Fujian Medical University between 2010 and 2018. The independent prognostic factors were selected by univariate and multivariate Cox regression analyses. The nomogram was constructed to predict individual survival outcomes for MBC patients. The discriminative power, calibration, and clinical effectiveness of the nomogram were evaluated by the concordance index (C-index), the receiver operating characteristic (ROC) curve, and the decision curve analysis (DCA). Results: MBC had a significantly higher T stage (T2 and above accounting for 75.1% vs 39.9%), fewer infiltrated lymph nodes (N0 accounted for 76.2% vs 67.7%), a lower proportion of ER (22.2% vs 81.2%), PR (13.6% vs 71.4%), and HER-2(6.7% vs 17.7%) positive, radiotherapy(51.6% vs 58.0%) but more chemotherapy(67.5% vs 44.7%), and a higher rate of mastectomy(53.2% vs 36.8%), which was discovered when comparing the clinical baseline data between MBC and IDC. Age at diagnosis, T, N, and M stage, as well as surgery and radiation treatment, were all significant independent prognostic factors for overall survival (OS). In the validation I cohort, the nomogram’s C-index (0.769 95% CI 0.710 -0.828) was indicated to be considerably higher than the standard AJCC model’s (0.700 95% CI 0.644 -0.756). Nomogram’s great predictive capability capacity further was supported by the comparatively high C-index of the validation II sets (0.728 95%CI 0.588-0.869). Conclusions: Metaplastic breast cancer is more aggressive, with a worse clinical prognosis than IDC. This nomogram is recommended for patients with MBC, both American and Chinese, which can help clinicians make more accurate individualized survival analyses. [ABSTRACT FROM AUTHOR]

The development of a city is not only a long-term process of material environment construction, but also a long-term process of cultural development and civilization accumulation. The essence of a city is that the city can provide people with a high-quality lifestyle: "valuable, meaningful, tasteful, dignified and dreamy". When a city's material civilization is built to a certain extent, the excessive materialization needs cultural harmony to be more perfect. The Capital of Culture in East Asia has rich cultural resources, and also excellent tourist cities. The core task of building the Capital of Culture in East Asia is to protect and utilize cultural resources fully, and promote the regeneration of urban cultural resources and cultural development. This study used research data derived from the relevant statistics officially released by the cities, and mainly using the case study with the Capital of Culture in East Asia in China as the example. Previous studies have shown that the realization of a city's cultural value is first to promote the regional development of the urban culture, so as to allow the residents to establish "Asian awareness" and "Asian vision", promote the development of urban culture in life, and increase opportunities for host and guest participation. On this basis, the spatial carrier of urban culture production, trade and consumption is built through the construction of urban culture space and the production of space. Finally, through the implementation of a brand strategy for the Capital of Culture in East Asia, the city's cultural space, cultural taste and consumption level will be improved, the city brand based on local culture and regional culture will be built, and its competitiveness will be achieved on both regional and global levels. [ABSTRACT FROM AUTHOR]

To quantify the pore characteristics of various macerals in Chang 7 lacustrine shales, macerals were effectively identified according to their optical and morphological characteristics, and the nanoscale pore structure of macerals was observed by scanning electron microscope. Meanwhile, the reflectances of different positions in the same pieces of vitrinite or solid bitumen with heterogeneous pores development were measured. The results showed that the average contents of sapropelinite, liptinite, vitrinite, inertinite and solid bitumen are 42.7%, 8.7%, 13.6%, 13.8% and 21.2%, respectively, which suggests that the source of the organic matter of the Chang 7 shales is a mixed source input. The organic pores of Chang 7 shales are enriched, and the pore shapes are mostly round or elliptical. The pore size of organic pores has a wide distribution, mainly concentrate in the range of 100e400 nm, and the average plane porosity of organic pores is 10.13%. The size order of the organic pores in various macerals is: solid bitumen < bituminite < alginite < vitrinite < fusinite < liptinite. The abundance order of organic matter pores of each maceral is as follows: alginite > fusinite > bituminite > solid bitumen > vitrinite > liptinite. OM pores are mainly contributed by bituminite, solid bitumen and fusinite. The plane porosity of bituminite increases with maturity. In the process of thermal evolution, the plane porosity of fusinite is distributed in the two ranges of 20%e28% and 1%e7%. The former is mainly the primary pores of the fusinite itself, and the latter is the secondary pores formed in the thermal evolution. As for the organic pores of other macerals, no obvious thermal evolution law was found. Meanwhile, the surface imperfections of vitrinite or solid bitumen is enhanced by the enrichment of organic pores (an increase in pore size or pore number), which may result in the underestimation of their reflectances. [ABSTRACT FROM AUTHOR]

Background: It is plausible that immunopathological processes associated with psoriasis might contribute to the occurrence of olfactory or taste dysfunction. However, the actual association was still unknown. Purpose: To determine the relationship between olfactory or taste dysfunction and psoriasis. Methods: Two cross-sectional studies were performed by using National Health and Nutrition Examination Survey (NHANES) data. Participants with psoriasis were defined as cases and those without psoriasis were identified as controls. Taste and smell self-reported questionnaires were used to define smell/taste alterations and identification tests were used to assure the smell/taste dysfunctions. Logistic regression models with inverse probability treatment weighting (IPTW) strategies were conducted to investigated the relationship between psoriasis and olfactory or taste dysfunction. Results: Self-reported questionnaires indicated that psoriasis patients were more likely to have perceived taste alteration (IPTW-aOR = 1.43) and smell alteration (IPTW-aOR = 1.22). Identification tests revealed that psoriasis was associated with taste dysfunction (IPTW-aOR = 1.28) and olfactory dysfunction (IPTW-aOR = 1.22). Relevant findings showed that psoriasis may be significantly associated with taste or olfactory dysfunction regardless of the questionnaire data or identification examination data used. Conclusion: Olfactory and taste dysfunction could be considered comorbidities in patients with psoriasis based on our observational study. Therefore, physicians should be cautious of olfaction and taste alterations among patients with psoriasis. [ABSTRACT FROM AUTHOR]

Background: The disruption of blood-brain barrier (BBB), predominantly made up by brain microvascular endothelial cells (BMECs), is one of the characteristics of Alzheimer's disease (AD). Thus, improving BMEC function may be beneficial for AD treatment. Tanshinone IIA (Tan IIA) has been proved to ameliorate the cognitive dysfunction of AD. Herein, we explored how Tan IIA affected the function of BMECs in AD. Methods: Aβ1–42-treated brain-derived endothelium cells.3 (bEnd.3 cells) was employed for in vitro experiments. And we performed molecular docking and qPCR to determine the targeting molecule of Tan IIA on Sirtuins family. The APPswe/PSdE9 (APP/PS1) mice were applied to perform the in vivo experiments. Following the behavioral tests, protein expression was determined through western blot and immunofluorescence. The activities of oxidative stress-related enzymes were analyzed by biochemically kits. Nissl staining and thioflavin T staining were conducted to reflect the neurodegeneration and Aβ deposition respectively. Results: Molecular docking and qPCR results showed that Tan IIA mainly acted on Sirtuin1 (SIRT1) in Sirtuins family. The inhibitor of SIRT1 (EX527) was employed to further substantiate that Tan IIA could attenuate SIRT1-mediated endoplasmic reticulum stress (ER stress) in BMECs. Behavioral tests suggested that Tan IIA could improve the cognitive deficits in APP/PS1 mice. Tan IIA administration increased SIRT1 expression and alleviated ER stress in APP/PS1 mice. In addition, LRP1 expression was increased and RAGE expression was decreased after Tan IIA administration in both animals and cells. Conclusion: Tan IIA could promote Aβ transportation by alleviating SIRT1-mediated ER stress in BMECs, which ameliorated cognitive deficits in APP/PS1 mice. [ABSTRACT FROM AUTHOR]

Seroclearance of hepatitis B surface antigen (HBsAg) is regarded as the functional cure for chronic hepatitis B (CHB). The relationship between human leukocyte antigen (HLA) variants, hepatitis B virus genotype, and longitudinal HBsAg serodecline remains to be explored. A total of 1735 HBeAg-seronegative CHB patients with genotype B or C infection of the community-based REVEAL-HBV cohort were genotyped for rs1710 (HLA-G) and rs2770 (HLA-B) using TaqMan assay. Cox proportional hazard regression and generalized linear mixed models were used to analyze the association of HLA genetic variants with the rate of HBsAg seroclearance and longitudinal HBsAg serodecline. Rs1710 G allele was differentially associated with the HBsAg seroclearance in genotype B [aRR (95% CI) = 0.74 (0.56–0.98)] and genotype C [aRR (95%CI) = 1.43 (1.08–1.88)] infection. Rs2770 G allele was associated with HBsAg seroclearance only in genotype B infection [aRR (95% CI) = 0.69 (0.52–0.91)]. The alleles associated with HBsAg seroclearance were significant predictors for the serodecline of HBsAg levels in an HBV genotype-dependent manner (genotype B infection: rs1710, P = 0.013; rs2770, P = 0.0081; genotype C infection: rs1710, P = 0.0452). Our results suggest both spontaneous HBsAg seroclearance and serodecline are modified by the interaction between HLA variants and HBV genotype. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii is a nosocomial pathogen associated with severe illness and death. Glucocorticoid aerosol is a common inhalation therapy in patients receiving invasive mechanical ventilation. We conducted a prospective cohort study to analyze the association between glucocorticoid aerosol therapy and A. baumannii isolation from ventilator patients in China. Of 497 enrolled patients, 262 (52.7%) received glucocorticoid aerosol, and A. baumannii was isolated from 159 (32.0%). Glucocorticoid aerosol therapy was an independent risk factor for A. baumannii isolation (hazard ratio 1.5, 95% CI 1.02-2.28; p = 0.038). Patients receiving glucocorticoid aerosol had a higher cumulative hazard for A. baumannii isolation and analysis showed that glucocorticoid aerosol therapy increased A. baumannii isolation in most subpopulations. Glucocorticoid aerosol was not a direct risk factor for 30-day mortality, but A. baumannii isolation was independently associated with 30-day mortality in ventilator patients. Physicians should consider potential A. baumannii infection when prescribing glucocorticoid aerosol therapy. [ABSTRACT FROM AUTHOR]

With the growing maturity of blockchain technology, its peer-topeer model and fully duplicated data storage pattern enable blockchain to act as a distributed ledger in untrustworthy environments. Blockchain storage has also become a research hotspot in industry, finance, and academia due to its security, and its unique data storage management model is gradually becoming a key technology to play its value in various fields' applications. However, with the increasing amount of data written into the blockchain, the blockchain system faces many problems in its actual implementation of the application, such as high storage space occupation, low data flexibility and availability, low retrieval efficiency, poor scalability, etc. To improve the above problems, this paper combines off-chain storage technology and deduplication technology to optimize the blockchain storage model. Firstly, this paper adopts the double-chain model to reduce the data storage of the major chain system, which stores a small amount of primary data and supervises the vice chain through an Application Programming Interface (API). The vice chain stores a large number of copies of data as well as non-transactional data. Our model divides the vice chain storage system into two layers, including a storage layer and a processing layer. In the processing layer, deduplication technology is applied to reduce the redundancy of vice chain data. Our doublechain storage model with high scalability enhances data flexibility, is more suitable as a distributed storage system, and performs well in data retrieval. [ABSTRACT FROM AUTHOR]

Taxifolin (TAX), as a natural flavonoid, has been widely focused on due to its strong anti-oxidation, anti-inflammation, anti-virus, and even anti-tumor activity. However, the effect of TAX on semen quality was unknown. The purpose of this study was to analyze the beneficial influences of adding feed additive TAX to boar semen in terms of its quality and potential mechanisms. We discovered that TAX increased sperm motility significantly in Duroc boars by the elevation of the protein levels such as ZAG, PKA, CatSper, and p-ERK for sperm quality. TAX increased the blood concentration of testosterone derivatives, antioxidants such as melatonin and betaine, unsaturated fatty acids such as DHA, and beneficial amino acids such as proline. Conversely, TAX decreased 10 different kinds of bile acids in the plasma. Moreover, TAX increased "beneficial" microbes such as Intestinimonas, Coprococcus, Butyrivibrio, and Clostridium_XlVa at the Genus level. However, TAX reduced the "harmful" intestinal bacteria such as Prevotella, Howardella, Mogibacterium, and Enterococcus. There was a very close correlation between fecal microbes, plasma metabolites, and semen parameters by the spearman correlation analysis. Therefore, the data suggest that TAX increases the semen quality of Duroc boars by benefiting the gut microbes and blood metabolites. It is supposed that TAX could be used as a kind of feed additive to increase the semen quality of boars to enhance production performance. [ABSTRACT FROM AUTHOR]

Our goal is to investigate the connection between serum 25(OH)D and carotid artery intima-media thickness (CIMT) in men with erectile dysfunction (ED). Serum 25(OH)D and CIMT were measured in 124 participants with erectile dysfunction and 39 healthy controls. The relationship between them and different patient-related parameters and disease-related parameters was studied. Compared with the control group and mild ED group, the level of serum 25(OH)D in moderate ED group and severe ED group decreased significantly(P<0.05). The CIMT values of moderate ED group and severe ED group were higher than those of the control group(P<0.05). The CIMT value of severe ED group was significantly higher than that of mild ED group (P<0.05). IIEF-5 score was positively correlated with serum 25(OH)D level, but negatively correlated with CIMT value(P<0.05). After adjusting for the influence of confounding factors, The CIMT values, 25(OH)D and IIEF-5 score were substantially associated (P<0.05). The serum level of 25(OH)D and IIEF-5 score were positively correlated, while the CIMT values and IIEF-5 score were negatively correlated. The level of serum 25(OH)D should be analyzed in men with ED, especially in patients with vasculogenic ED, and supplementation is recommended for those who were with vitamin D deficiency. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of weight loss on pregnancy outcomes, PCOS related neuronal-reproductive-metabolic hormones and ovarian granulosa cell gene expression profiles in obese PCOS infertile patients undergoing in vitro fertilization-embryo transfer (IVF-ET). Methods: 75 patients undergoing IVF-ET due to tubal factors alone collected as the control group (group A), and 352 patients with obese PCOS infertility were divided into four groups according to the amount of weight loss before IVF: 0 kg (group B), 1-5 kg (group C), 5-10 kg (group D), and >10 kg (group E). Six cases of ovarian granulosa cells were collected randomly with the random number table method in each group for detecting mRNA profiling. Pathway networks and biological functions of the differentially expressed genes were analyzed. Validation by RT-PCR was performed. Results: (1) The levels of luteinizing hormone(LH), testosterone(T) and homeostasis model assessment insulin resistance(HOMA-IR) in group E were significantly lower than those in groups B and C (P<0.05). (2) Compared with groups A and E, groups B and C showed increased total gonadotropin (Gn) and days of Gn stimulation (P<0.05), and the E2 level on trigger day and number of oocytes obtained in group B was significantly less than that in group E (P<0.05 or 0.01). Embryo implantation rate, clinical pregnancy rate and live birth rate were increased and miscarriage rate was decreased in groups A, D and E compared with group B (P<0.05 or 0.01). (3) There were significant differences among the control group and PCOS groups in some genes that are involved in neuronal-reproductive-metabolic endocrine, transcriptional regulation, cell proliferation and differentiation, etc (P<0.05). RNA-Seq results were validated by real time PCR analysis for the expression of follicle stimulating hormone receptor (FSHR), drosophila mothers against decapentaplegic protein 7(Smad7) and glutathione peroxidase 3(GPX3) genes that are known to have an important role in follicular development. Functional alterations were confirmed by the improvement in the ovarian responsiveness to Gn and embryo quality. Conclusion: Weight loss more than 5kg may regulate the neuroreproductive endocrine hormone secretion, insulin resistance and gene expression profiles of ovarian granulosa cells, so as to improve the ovarian responsiveness to Gn, the embryo quality, embryo implantation rate, clinical pregnancy rate, live birth rate, and reduce the spontaneous abortion rate in obese infertile PCOS patients undergoing IVF-ET. [ABSTRACT FROM AUTHOR]

Background: With the continued advancement of RNA-seq (RNA-sequencing), microRNA (miRNA) editing events have been demonstrated to play an important role in different malignancies. However, there is yet no description of the miRNA editing events in recurrent bladder cancer. Objective: To identify and compare miRNA editing events in primary and recurrent bladder cancer, as well as to investigate the potential molecular mechanism and its impact on patient prognosis. Methods: We examined the mRNA and miRNA transcriptomes of 12 recurrent bladder cancer cases and 13 primary bladder cancer cases. The differentially expressed mRNA sequences were analyzed. Furthermore, we identified the differentially expressed genes (DEGs) in recurrent bladder cancer. The Gene Ontology (GO) functional enrichment analyses on DEGs and gene set enrichment analysis were performed. The consensus molecular subtype (CMS) classification of bladder cancer was identified using the Consensus MIBC package in R (4.1.0); miRNA sequences were then further subjected to differentially expressed analysis and pathway enrichment analysis. MiRNA editing events were identified using miRge3.0. miRDB and TargetScanHuman were used to predict the downstream targets of specific differentially edited or expressed miRNAs. The expression levels of miR-154-5p and ADAR were validated by RT-qPCR. Finally, survival and co-expression studies were performed on the TCGA-BLCA cohort. Results: First, the mRNA expression levels in recurrent bladder cancer changed significantly, supporting progression via related molecular signal pathways. Second, significantly altered miRNAs in recurrent bladder cancer were identified, with miR-154-5p showing the highest level of editing in recurrent bladder cancer and may up-regulate the expression levels of downstream targets HS3ST3A1, AQP9, MYLK, and RAB23. The survival analysis results of TCGA data revealed that highly expressed HS3ST3A1 and RAB23 exhibited poor prognosis. In addition, miR-154 editing events were found to be significant to CMS classification. Conclusion: MiRNA editing in recurrent bladder cancer was detected and linked with poor patient prognosis, providing a reference for further uncovering the intricate molecular mechanism in recurrent bladder cancer. Therefore, inhibiting A-to-I editing of miRNA may be a viable target for bladder cancer treatment, allowing current treatment choices to be expanded and individualized. [ABSTRACT FROM AUTHOR]