Cu/TiO2 adsorbents modified by air plasma for adsorption-oxidation of H2S.

In this study, non-thermal plasma (NTP) was employed to modify the Cu/TiO2 adsorbent to efficiently purify H2S in low-temperature and micro-oxygen environments. The effects of Cu loading amounts and atmospheres of NTP treatment on the adsorption-oxidation performance of the adsorbents were investigated. The NTP modification successfully boosted the H2S removal capacity to varying degrees, and the optimized adsorbent treated by air plasma (Cu/TiO2-Air) attained the best H2S breakthrough capacity of 113.29 mg H2S/gadsorbent, which was almost 5 times higher than that of the adsorbent without NTP modification. Further studies demonstrated that the superior performance of Cu/TiO2-Air was attributed to increased mesoporous volume, more exposure of active sites (CuO) and functional groups (amino groups and hydroxyl groups), enhanced Ti-O-Cu interaction, and the favorable ratio of active oxygen species. Additionally, the X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) results indicated the main reason for the deactivation was the consumption of the active components (CuO) and the agglomeration of reaction products (CuS and SO42-) occupying the active sites on the surface and the inner pores of the adsorbents.

The relationship between serum monoterpene levels and bone health: a retrospective cross-sectional analysis from the National Health and Nutrition Examination Survey (NHANES) data.

Introduction: Monoterpenes, a subset of the terpene family composed of two isoprene units, have garnered significant attention in research circles owing to their potential medicinal benefits. Recent experimental studies indicate that they might exert positive effects on bone health. Nevertheless, the impact of monoterpenes exposure on bone health remains unexplored in humans. Methods: We examined 748 adults (age ≥ 40 years) from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 to explore the correlation between three monoterpenes (α-pinene, ß-pinene, and limonene), bone mineral density (BMD) in the total lumbar spine and proximal femur, FRAX® scores, and prior bone fracture history. Results and discussion: Our analysis unveiled a significant inverse association between a one-unit increase in the natural logarithm (ln) of α-pinene and limonene and total proximal femur BMD (ß = -0.027, S.E. = 0.008, P = 0.004 and ß = -0.019, S.E. = 0.007, P = 0.016, respectively). As serum α-pinene levels ascended across quintiles, there was a notable decrease in total proximal femur BMD (P for trend = 0.025). The inverse relationship between ln α-pinene levels and total proximal femur BMD was more pronounced in women, especially pre-menopausal women. Compared to subjects with α-pinene and limonene levels at or below the 50th percentiles, those exceeding this threshold exhibited the lowest mean value of total proximal femur BMD (0.8628 g/cm2, S.E. = 0.026, P = 0.009). However, the trend was not statistically significant (P = 0.070). Additionally, all three monoterpenes were linked to a higher prevalence of previous spine fractures, whereas ß-pinene showed a reduced incidence of other types of fractures. In this comprehensive survey of American adults aged 40 and above, higher serum levels of α-pinene and limonene correlated with decreased total proximal femur BMD. Furthermore, our findings suggest a potential combined effect of α-pinene and limonene on total proximal femur BMD. Further investigation is essential to elucidate the clinical relevance and causative nature of our findings.

A Psychometric Development and Evaluation of the Flow State Scale for Caregiving Tasks Among Clinical Nurses.

BACKGROUND: The extensive research already conducted in numerous non-healthcare disciplines has consistently demonstrated the effectiveness of flow in alleviating work-related stress and boosting employee engagement in the workplace. Despite the potential benefits to nursing of improving flow, no valid instrument is currently available to measure the work-related flow experience of clinical nurses. PURPOSE: This study was designed to develop the Flow State Scale for Caregiving Tasks (FSS-CT) and to evaluate its psychometric properties in the context of clinical nurses. METHODS: This study, guided by the flow theory of Mihaly Csikszentmihalyi (1975), employed a three-phase approach to developing and evaluating the psychometric properties of the FSS-CT. Five hundred thirty-six full-time clinical nurses working in hospitals of various levels in Taiwan were recruited via cluster random sampling to participate in an anonymous online survey. The content validity of the developed scale was established through expert panel verification, criterion-related validity was assessed by correlating the scale with the Work-related Flow Inventory, and construct validity was evaluated via explanatory and confirmatory factor analyses. Scale reliability was determined using Cronbach's α coefficient. RESULTS: The FSS-CT, a 12-item Likert scale comprising four domains, was developed. These domains capture the elements of nurses' work-related flow, including professional confidence, merging of action and awareness, balance between skill and challenge, and autotelic experience. The FSS-CT demonstrated high content validity (content validity index > .90) and satisfactory criterion-related validity (coefficient = .55, p < .001). Furthermore, the scale was found to have excellent internal consistency (Cronbach's α = .91). Factor analyses yielded a four-factor structure accounting for 69.34% of the total variance, indicating a good fit for the final model based on recommended goodness-of-fit indices. CONCLUSIONS: The FSS-CT is a viable and dependable instrument for assessing the work-related flow experiences of nurses, with the measured outcomes offering to nursing administrators valuable insights into or directions for personnel development and work allocation initiatives.

Zishen Qingre Lishi Huayu Recipe May Ameliorate the Symptoms of PCOS Model Rats via Alleviating Systemic and Ovarian Inflammation.

BACKGROUND: Zishen Qingre Lishi Huayu recipe (ZQLHR) has shown significant therapeutic effects in treating sex hormone levels and follicular developmental disorders in patients with polycystic ovary syndrome (PCOS). However, little is known about the potential mechanisms of its treatment. METHODS: Dehydroepiandrosterone and a high-fat diet induced the PCOS model rat. The serum of rats was collected to detect the levels of sex hormones and inflammatory cytokines by enzyme-linked immunosorbent assay, and the ovaries were collected for ovarian histopathology and qPCR assay to detect the levels of inflammatory cytokines in ovarian tissues. Granulosa cells (GCs) were collected for western blot assay to detect of IL-1ß, IL-6R, and LOX protein expression levels. RESULTS: ZQLHR could reduce body weight, regulate estrous cycles, and improve serum sex hormone levels, follicular development, and insulin resistance (IR) in PCOS model rats. In addition, ZQLHR treatment improved the levels of inflammatory cytokines in serum and ovary, and regulated the protein expression of IL-6R, IL-1ß, and LOX in GCs of PCOS model rats. The results showed that the HOMA-IR index increased with the increasing levels of IL-6, IL-1ß, and CRP, and decreased with the increased IL-10. CONCLUSION: This study reveals that the treatment of endocrine disorders and ovulation disorders in PCOS with ZQLHR may be closely related to the improvement of systemic and ovarian inflammation in PCOS patients, as well as the inhibition of IL-6R, IL-1ß, and LOX expression in GCs, which reemphasizes the role of reducing chronic inflammatory states in the treatment of PCOS. Moreover, this study reemphasizes the correlation between multiple inflammatory mediators and IR.

Association of Estimated Glomerular Filtration Rate Trajectories with Atrial Fibrillation Risk in Populations with Normal or Mildly Impaired Renal Function.

Introduction: The association between the longitudinal patterns of estimated glomerular filtration rate (eGFR) and risk of atrial fibrillation (AF) in populations with normal or mildly impaired renal function is not well characterized. We sought to explore the eGFR trajectories in populations with normal or mildly impaired renal function and their association with AF. Methods: This prospective cohort study included 62,407 participants who were free of AF, cardiovascular diseases, and moderate to severe renal insufficiency (eGFR <60 mL/min/1.73 m2) before 2010. The eGFR trajectories were developed using latent mixture modeling based on examination data in 2006, 2008, and 2010. Incident AF cases were identified in biennial electrocardiogram assessment and a review of medical insurance data and discharge registers. We used Cox regression models to estimate the hazard ratios and 95% confidence intervals (CIs) for incident AF. Results: According to survey results for the range and changing pattern of eGFR during 2006-2010, four trajectories were identified: high-stable (range, 107.47-110.25 mL/min/1.73 m2; n = 11,719), moderate-increasing (median increase from 83.83 to 100.37 mL/min/1.73 m2; n = 22,634), high-decreasing (median decrease from 101.72 to 89.10 mL/min/1.73 m2; n = 7,943), and low-stable (range, 73.48-76.78 mL/min/1.73 m2; n = 20,111). After an average follow-up of 9.63 years, a total of 485 cases of AF were identified. Compared with the high-stable trajectory, the adjusted hazard ratios of AF were 1.70 (95% CI, 1.09-2.66) for the moderate-increasing trajectory, 1.92 (95% CI, 1.18-3.13) for the high-decreasing trajectory, and 2.28 (95% CI, 1.46-3.56) for the low-stable trajectory. The results remained consistent across a number of sensitivity analyses. Conclusion: The trajectories of eGFR were associated with subsequent AF risk in populations with normal or mildly impaired renal function.

The relation between estimated glomerular filtration rate (eGFR) within the normal or mildly impaired range and risk of atrial fibrillation (AF) in former studies is controversial, and data on longitudinal pattern of eGFR in such topic is sparse. In this cohort study, we identified 4 trajectories of eGFR in populations with normal or mildly impaired renal function. Relative to populations with high-stable pattern of eGFR, those with low-stable pattern, high-decreasing pattern and moderate-increasing pattern were associated with 128%, 92%, and 70% higher risk of AF, respectively. These findings suggested that monitoring eGFR trajectories is an important approach for AF prediction in populations with normal or mildly impaired renal function. Decreasing and consistently low eGFR trajectories within the currently designated normal or mildly impaired range may still significantly increase the risk of AF.

Treatment Outcomes of Intralesional Steroid Injection for Refractory Vocal Process Granuloma.

OBJECTIVES: Vocal process granuloma (VPG) is a chronic condition resulting from a mucoperichondrial injury of vocal process. Initial conservative treatment typically involves vocal hygiene education and antireflux medication. Treatment challenges arise with refractory cases. Outcomes of second-line treatments such as surgical excision and botulinum toxin injections remain inconsistent. Thus, we propose this study to investigate the effectiveness of intralesional steroid injections for refractory VPG. METHODS: We conducted a retrospective review of 23 patients with VPG who showed no improvement after 3 months of proton pump inhibitors. These patients underwent one to three courses of monthly in-office intralesional steroid injections as a second-line therapy. Treatment outcomes were evaluated by measuring the size of the VPG relative to the length of the vocal folds before and after the final injection procedure. RESULTS: Results showed a significant reduction in VPG size from baseline of 27.74 ± 15.06 to 5.48 ± 8.95 (p < .001). 15 out of 23 patients were responsive (size reduction ≥ 75%) to intralesional steroid injection. Alcohol consumption and longer symptom duration were associated with a poor response (size reduction <75%), whereas prior intubation was associated with better response. CONCLUSIONS: For refractory VPG not responding to conservative treatment, intralesional steroid injection appears to be a promising alternative option without significant adverse effects.

Pleiotropic regulatory locus 1 maintains actin cytoskeleton integrity and cellular homeostasis to enable Arabidopsis root growth.

Cell functions are based on the integrity of actin filaments. The actin cytoskeleton is typically the target but also the source of signals. Arabidopsis PRL1 (Pleiotropic Regulatory Locus 1), regulates multiple cellular processes and physiological responses. However, the precise mechanisms underlying PRL1`s multiple functions are unclear. Here, we show that PRL1 maintains actin integrity and concomitant cellular homeostasis. The cortical actin cytoskeleton was de-polymerized in the prl1 mutant, causing the developmental root defect. Actin depolymerization, rather than reactive oxygen species (ROS) imbalance, constituted the fundamental cause of retarded root growth in prl1. ANAC085 upregulation by, and cooperation with, actin depolymerization triggered stele cell death in prl1 roots. Differential gene expression and alternative splicing defects resulting from actin depolymerization occurred independently in prl1. Our work establishes the cause-effect relationships between actin depolymerization and downstream stress-related signals, revealing a novel function of PRL1 and enhancing the understanding of PRL`s functional mechanisms.

Shallow groundwater table fluctuations weaken nitrogen accumulation in the thin layer vadose zone of cropland around plateau lakes, Southwest China.

Excessive accumulation of nitrogen (N) in the soil profile in the intensive agricultural region will seriously threaten groundwater quality and safety. However, the impact of shallow groundwater table (SGWT) fluctuations driven by seasonal variations on the N accumulation characterizations in the soil profiles has not been well quantified, particularly in the regions with thin layer vadose zone. Through in-situ monitoring and simulation experiments, the changes in the SGWT and N accumulation of soil profile in intensive cropland around 7 plateau lakes in Yunnan were studied during the rainy season (RS) and dry season (DS), and the N loss in soil profile of cropland driven by SGWT fluctuations was estimated. The results showed that the SGWT and N accumulation in soil profile of cropland around the plateau lakes had obvious seasonal variation characteristics. The proportion of N storage in different forms in 60-100 cm soil layer in the RS was greater than that in the DS, particularly the proportion of NH4+-N storage was as high as 55 %, while N accumulation in surface soil was obvious in the DS. Compared with the DS, due to the rising SGWT in the RS, the maximum storages of TN and NO3--N in the 0-100 cm soil layer decreased by17% and 36 %, respectively. The TN loss intensities from the 0-100 cm soil profiles of cropland around Fuxian Lake, Yilong Lake, Qilu Lake, Dianchi Lake, Yangzong Lake, Erhai Lake, and Xingyun Lake were 74, 54, 127, 105, 93, 72 and 207 kg/ha, respectively. Moreover, if the SGWT was <30 cm, the average TN loss intensity and amount could reach 177 kg/ha and 1250 t, respectively. Therefore, the SGWT regulation was one of the key measures to reducing soil N loss from the thin layer vadose zone of cropland around plateau lakes and improving groundwater quality.

Traditional Chinese medicine constitution and sarcopenia: a cross-sectional study.

Objective: Sarcopenia is a gradually advancing systemic disorder affecting skeletal muscles, primarily distinguished by diminished muscle mass and functional decline. As of present, a universally accepted diagnostic criterion for sarcopenia has yet to be established. From the perspective of the constitution theory in traditional Chinese medicine (TCM), the Yin-deficiency constitution is believed to have a significant correlation with the development of sarcopenia. The primary objective of this study was to examine the potential association between sarcopenia and Yin-deficiency constitution. Methods: The present study is a cross-sectional analysis. The Asian Working Group for Sarcopenia (AWGS) recommended a diagnostic criterion for sarcopenia. A total of 141 participants over 50 years of age were diagnosed with sarcopenia. To determine the constitution of each patient, classification and determination standards were used in traditional Chinese medicine. In this study, a combination of logistic regression and propensity score matching (PSM) was employed to analyze a dataset comprising 1,372 eligible observations. The diagnostic efficacy of the test in distinguishing sarcopenia was assessed through receiver operating characteristic (ROC) curve analysis. Results: The relationship between Yin-deficiency constitution and sarcopenia was examined using logistic regression analysis. In the crude model, the odds ratio (OR) was found to be 3.20 (95% confidence interval [CI]: 1.70-6.03). After adjusting for various confounding factors, including gender, sex, 6 m walking test/(m/s), SMI, and maximum grip strength/kg, the OR increased to 9.70 (95% CI: 3.20-69.38). The associations between seven other biased traditional Chinese medicine (TCM) constitutions and sarcopenia were not found to be statistically significant in the fully adjusted model. The propensity score matching (PSM) analysis yielded consistent results with the logistic regression analysis. Receiver operating characteristic (ROC) curve analysis showed that the AUC of the Yin-deficiency constitution combined with age and gender reached 0.707. Conclusion: Among the nine TCM constitutions examined, the Yin-deficiency constitution demonstrates an independent association with sarcopenia. Yin-deficiency constitution may serve as a potential risk factor for the development of sarcopenia. To establish a causal relationship, further experimental investigations are warranted. The diagnostic performance of sarcopenia is effectively demonstrated by the Yin-deficiency constitution combined with age and gender.

The original scores of traditional Chinese medicine constitutions are risk and diagnostic factors in middle-aged and older adults with sarcopenia.

Objective: Sarcopenia is a geriatric syndrome that occurs with age and is characterized by a gradual decline in muscle mass, power, and functionality. It serves as a prominent contributor to frailty, disability, and mortality among older individuals. Currently, no standardized global guidelines exist for the diagnosis of sarcopenia. This study aimed to establish the correlation between sarcopenia and the constitutions of traditional Chinese medicine (TCM), considering the connection between physical functioning and sarcopenia. Methods: A total of 1441 participants in this study were diagnosed with sarcopenia. The Asian Working Group for Sarcopenia (AWGS) proposed a sarcopenia definition algorithm. To determine the constitution of each participant, classification and determination standards were used in traditional Chinese medicine. This study evaluated the demographics, lifestyles, and self-reported medical history of individuals diagnosed with sarcopenia through a self-administered questionnaire. The constitution of the participants was determined using TCM classification and determination standards. Subsequently, we analyzed the results of univariate analysis and multivariate regression and constructed a receiver operating characteristic (ROC) curve. Results: Participants who were diagnosed with sarcopenia had substantially lower original Neutral constitution scores (P < 0.050). In comparison to those without sarcopenia, individuals with sarcopenia exhibited notably elevated original Qi-deficiency, Yang-deficiency, Yin-deficiency, Blood-stagnation, and Qi-stagnation scores in contrast to those in the healthy group (P < 0.050). The identified risk factors associated with sarcopenia included the following: Neutral (OR = 0.903), Qi-deficiency (in males, OR = 1.126), Yang-deficiency (OR = 1.062), Phlegm-dampness (in males, OR = 0.833), and Blood-stagnation (in females, OR = 1.089). The highest area under the curve (AUC) was observed for the original neutral constitution score, followed by the Yang-deficiency and blood-stagnation scores (0.644, 0.613, and 0.611, respectively). Additionally, the AUC for the combined original scores of all nine constitutions among males reached 0.778. Conclusions: In this cross-sectional study of older people with higher original Qi-deficiency, Yin deficiency, Yang-deficiency, Blood-stagnation, and Qi-stagnation were associated with sarcopenia. Notably, various TCM constitutions are significantly linked to sarcopenia. There was a significant occurrence of various body constitution types among individuals diagnosed with sarcopenia. The mixture of the nine original constitution scores exhibited good diagnostic performance for sarcopenia in males.

Evaluation of the efficacy and quality of life in patients with temporomandibular joint disorders treated with Kovacs digital occlusal splint: a pilot study.

BACKGROUND: Few studies have been conducted on treating temporomandibular disorders (TMDs) with new digital occlusal splints, which has increasingly attracted wide attention. METHODS: To evaluate the clinical efficacy and quality of life (QoL) of Kovacs digital occlusal splint (KDOS) treatment in patients with TMD. MATERIALS AND METHODS: Eighty-nine patients with TMD who were treated using KDOS were analyzed. The patients were divided into three groups according to the Wilkes stage. The clinical symptoms and QoL scores of the patients in each group were recorded before and at least three months after treatment, and the data were statistically analyzed and compared. The relationships between the disease severity, sex, age, and level of QoL before treatment and improvement in the clinical symptoms were analyzed using binary logistic regression. RESULTS: The mean age and follow-up period of the patients were 28.0 ± 10.4 years and 4.9 ± 2.1 months, respectively. After KDOS treatment, the improvement rates of joint noise and pain were 80.4% and 69.8%, respectively. Additionally, the patients' maximum mouth opening and global QoL mean scores significantly improved compared to those before treatment (p < 0.001). Binary logistic regression analysis revealed that the factors affecting the improvement in the clinical symptoms were disease severity and level of QoL before treatment. CONCLUSIONS: KDOS can improve the clinical symptoms and QoL of patients with TMD. Moreover, patients without osteoarthritis and with low pretreatment QoL levels are more likely to demonstrate clinical improvement. TRIAL REGISTRATION: The trial was registered with Chinese Clinical Trial Registry (ChiCTR) (ID: ChiCTR2300076518) on 11/10/2023.

Kidney outcomes with SGLT2is for type 2 diabetes patients: does background treatment with metformin or RASis matter?

Introduction: There is a lack of real-world evidence regarding the impact of concomitant metformin and renin-angiotensin system inhibitors (RASis) on sodium-glucose cotransporter-2 inhibitor (SGLT2i)-associated kidney outcomes. This study was aimed to investigate whether SGLT2i-associated kidney outcomes were modified by the concomitant use of metformin or RASis in patients with type 2 diabetes. Methods: SGLT2i users were identified from three electronic health record databases during May 2016 and December 2017 and categorized into those with and without concomitant use of metformin or RASis. Propensity score matching was performed to minimize baseline differences between groups. Study outcomes were mean estimated glomerular filtration rate (eGFR) change and time to 30%, 40%, and 50% eGFR reductions. A meta-analysis was performed to combine the estimates across databases. Results: After matching, there were 6,625 and 3,260 SGLT2i users with and without metformin, and 6,654 and 2,746 SGLT2i users with and without RASis, respectively. The eGFR dip was similar in SGLT2i users with and without metformin therapy, but was greater in SGLT2i users with RASis compared to those without RASis. Neither metformin nor RASi use had a significant effect on SGLT2i-associated eGFR reductions, as evidenced by the hazard ratios (95% CIs) of 30% eGFR reductions for SGLT2is with versus without metformin/RASis, namely 1.02 (0.87-1.20)/1.09 (0.92-1.31). Such findings were also observed in the outcomes of 40% and 50% eGFR reductions. Conclusion: Using metformin or RASis did not modify SGLT2i-associated kidney outcomes in type 2 diabetes.

A Probabilistic Approach to Estimate the Temporal Order of Pathway Mutations Accounting for Intra-Tumor Heterogeneity.

The development of cancer involves the accumulation of somatic mutations in several essential biological pathways. Delineating the temporal order of pathway mutations during tumorigenesis is crucial for comprehending the biological mechanisms underlying cancer development and identifying potential targets for therapeutic intervention. Several computational and statistical methods have been introduced for estimating the order of somatic mutations based on mutation profile data from a cohort of patients. However, one major issue of current methods is that they do not take into account intra-tumor heterogeneity (ITH), which limits their ability to accurately discern the order of pathway mutations. To address this problem, we propose PATOPAI, a probabilistic approach to estimate the temporal order of mutations at the pathway level by incorporating ITH information as well as pathway and functional annotation information of mutations. PATOPAI uses a maximum likelihood approach to estimate the probability of pathway mutational events occurring in a specific sequence, wherein it focuses on the orders that are consistent with the phylogenetic structure of the tumors. Applications to whole exome sequencing data from The Cancer Genome Atlas (TCGA) illustrate our method's ability to recover the temporal order of pathway mutations in several cancer types.

Proteomics approach to discovering non-invasive diagnostic biomarkers and understanding the pathogenesis of endometriosis: a systematic review and meta-analysis.

BACKGROUND: Endometriosis is one of the most common gynaecological diseases, yet it lacks efficient biomarkers for early detection and unravels disease mechanisms. Proteomic profiling has revealed diverse patterns of protein changes in various clinical samples. Integrating and systematically analysing proteomics data can facilitate the development of biomarkers, expediting diagnosis and providing insights for potential clinical and therapeutic applications. Hence, this systematic review and meta-analysis aimed to explore potential non-invasive diagnostic biomarkers in various biological samples and therapeutic targets for endometriosis. METHODS: Online databases, including Scopus, PubMed, Web of Science, MEDLINE, Embase via Ovid, and Google Scholar, were searched using MeSH terms. Two independent authors screened the articles, extracted the data, and assessed the methodological quality of the included studies. GO and KEGG analyses were performed to identify the pathways that were significantly enriched. Protein­protein interaction and hub gene selection analyses were also conducted to identify biomarker networks for endometriosis. RESULTS: Twenty-six observational studies with a total of 2,486 participants were included. A total of 644 differentially expressed proteins (180 upregulated and 464 downregulated) were identified from 9 studies. Proteins in peripheral blood exhibited a sensitivity and specificity of 38-100% and 59-99%, respectively, for detecting endometriosis, while proteins in urine had a sensitivity of 58-91% and specificity of 76-93%. Alpha-1-antitrypsin, albumin, and vitamin D binding proteins were significantly DEPs in both serum and urine. Complement C3 is commonly expressed in serum, menstrual blood, and cervical mucus. Additionally, S100-A8 is commonly expressed in both menstrual blood and cervical mucus. Haptoglobin is commonly detected in both serum and plasma, whereas cathepsin G is found in urine, serum, and plasma. GO and KEGG enrichment analyses revealed that proteoglycans in cancer pathways, which regulate cell-to-cell interactions, modulate the extracellular matrix, and promote the proliferation and invasion of endometrial cells, are commonly enriched in serum and urine. CONCLUSION: This comprehensive study revealed potential proteomes that were significantly differentially expressed in women with endometriosis utilizing various non-invasive clinical samples. Exploring common differentially expressed proteins in various biological samples provides insights into the diagnosis and pathophysiology of endometriosis, as well as potential clinical and therapeutic applications.

Elevating PLK1 overcomes BETi resistance in prostate cancer via triggering BRD4 phosphorylation-dependent degradation in mitosis.

Bromodomain-containing protein 4 (BRD4) has emerged as a promising therapeutic target in prostate cancer (PCa). Understanding the mechanisms of BRD4 stability could enhance the clinical response to BRD4-targeted therapy. In this study, we report that BRD4 protein levels are significantly decreased during mitosis in a PLK1-dependent manner. Mechanistically, we show that BRD4 is primarily phosphorylated at T1186 by the CDK1/cyclin B complex, recruiting PLK1 to phosphorylate BRD4 at S24/S1100, which are recognized by the APC/CCdh1 complex for proteasome pathway degradation. We find that PLK1 overexpression lowers SPOP mutation-stabilized BRD4, consequently rendering PCa cells re-sensitized to BRD4 inhibitors. Intriguingly, we report that sequential treatment of docetaxel and JQ1 resulted in significant inhibition of PCa. Collectively, the results support that PLK1-phosphorylated BRD4 triggers its degradation at M phase. Sequential treatment of docetaxel and JQ1 overcomes BRD4 accumulation-associated bromodomain and extra-terminal inhibitor (BETi) resistance, which may shed light on the development of strategies to treat PCa.

IL-2, IL-17A and TNF-α hold potential as biomarkers for predicting acute mountain sickness prior to ascent.

BACKGROUND: Acute mountain sickness (AMS) is the most prevalent condition resulting from hypobaric hypoxia (HH) at high altitudes. Although evidence suggests the involvement of inflammatory cytokines in AMS development, there is currently a lack of reports on variations in cytokine levels between individuals susceptible to AMS and those resistant to AMS prior to ascending to high altitude. Thus our current study aims to assess the predictive capability for AMS occurrence by evaluating differences in cytokine levels at low altitudes. METHODS: The present study recruited 48 participants, who ascended from low altitude to middle high-altitude (3700 m) and further to extreme high-altitude (5000 m). Based on Lake Louise Score (LLS) at the two high altitudes, participants were categorized into severe AMS-susceptible (sAMS), moderate AMS-susceptible (mAMS), and non-AMS groups. The Bio-Plex MAGPIX System was employed to measure plasma levels of 11 inflammatory cytokines. Cytokines at low altitude and middle high-altitude were analyzed through receiver operating characteristic (ROC) analysis to obtain area under the ROC curve (AUROC), sensitivity, and specificity. RESULTS: Based on LLS at 3700 m, we initially categorized the study subjects into the sAMS group (n = 8) and the Non-AMS group (n = 40). Among individuals in the non-AMS group (n = 40) at the altitude of 3700 m, those who developed AMS at the altitude of 5000 m were assigned to the mAMS group (n = 17), whereas those who did not experience AMS were included into the non-AMS group (n = 23). The concentration of TNF-α at low altitude exhibited robust predictive performance for predicting AMS occurrence at the altitude of 3700 m. Among the non-AMS group at the altitude of 3700 m, we identified that the concentration of IL-2 and IL-17A demonstrated high efficacy in predicting the onset of AMS following ascent to 5000 m. In addition, differentially expressed cytokines including IL-17A, TNF-α and IL-2 at low altitude possessed discriminatory potential among the three groups at 5000 m.. CONCLUSION: We posited that the levels of TNF-α, IL-2, IL-17A in serum of low altitude could be considered as potential biomarkers to predict the occurrence of AMS at high altitude. NEW & NOTEWORTHY: Through the two comparisons at different two altitudes (baseline level and 3700 m), we provided a model to progressively screen individuals who are susceptible and resistant to different high altitudes (3700 m and 5000 m). TNF-α could firstly screen out the AMS susceptible individuals at the altitude of 3700 m. And through its combination with IL-2 and IL-17A, we could further screen out AMS susceptible individuals at the altitude of 5000 m.

Antibiotic use and risk of autism spectrum disorder and attention-deficit/hyperactivity disorder: a population-based cohort study.

BACKGROUND: The gut microbiota is believed to influence neurodevelopment through the gut-brain axis, but prior studies have shown inconsistent results regarding early childhood antibiotic exposure and subsequent risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). The purpose of this study was to evaluate the hypothesis that exposure to antibacterial agents in the first 2 years of life increases the risk of ASD and/or ADHD. METHODS: This was a retrospective cohort study using 2003-2019 data from the National Health Insurance Research Database in Taiwan. Livebirths born between 2004 and 2016 were identified and separated into singleton, full sibling, and exposure-discordant sibling pair cohorts. The exposure group included children who filled at least one prescription for antibacterial agents between 0 and 2 years old in outpatient settings. The outcome, ASD and/or ADHD, was defined by at least one inpatient or outpatient diagnosis. The maximum follow-up age was 15 years in this study. Potential neonatal, maternal and paternal confounders were adjusted for. Cox proportional hazards models were used to estimate the relative event risk. RESULTS: The final sample contained 946,581 children in the singleton cohort, 1,142,693 children in the full sibling cohort, and 352,612 children in the exposure-discordant sibling pair cohort. Antibiotic exposure marginally increased the risk of ASD and/or ADHD in the singleton cohort (adjusted hazard ratio [aHR]: 1.06, 95% confidence interval [CI]: 1.04-1.07) and in the full sibling cohort (aHR: 1.03, 95% CI: 1.01-1.04). A slight decrease in the risk of ASD and/or ADHD was observed in the exposure-discordant sibling pair cohort (aHR: 0.92, 95% CI: 0.90-0.94). CONCLUSIONS: The results suggest that early life antibiotic exposure has minimal impact on the risk of ASD and/or ADHD. Given that the estimated effects are marginal and close to null, concerns about ASD and/or ADHD risk increase should not postpone or deter timely and reasonable antibiotic use.

The Therapeutic Role of NPS-1034 in Pancreatic Ductal Adenocarcinoma as Monotherapy and in Combination with Chemotherapy.

Pancreatic ductal adenocarcinoma (PDAC) poses a significant challenge in terms of diagnosis and treatment, with limited therapeutic options and a poor prognosis. This study explored the potential therapeutic role of NPS-1034, a kinase inhibitor targeting MET and AXL, in PDAC. The investigation included monotherapy with NPS-1034 and its combination with the commonly prescribed chemotherapy agents, fluorouracil and oxaliplatin. Our study revealed that NPS-1034 induces cell death and reduces the viability and clonogenicity of PDAC cells in a dose-dependent manner. Furthermore, NPS-1034 inhibits the migration of PDAC cells by suppressing MET/PI3K/AKT axis-induced epithelial-to-mesenchymal transition (EMT). The combination of NPS-1034 with fluorouracil or oxaliplatin demonstrated a synergistic effect, significantly reducing cell viability and inducing tumor cell apoptosis compared to monotherapies. Mechanistic insights provided by next-generation sequencing indicated that NPS-1034 modulates immune responses by inducing type I interferon and tumor necrosis factor production in PDAC cells. This suggests a broader role for NPS-1034 beyond MET and AXL inhibition, positioning it as a potential immunity modulator. Overall, these findings highlight the anticancer potential of NPS-1034 in PDAC treatment in vitro, both as a monotherapy and in combination with traditional chemotherapy, offering a promising avenue for further in vivo investigation before clinical exploration.

Adaptation of risk prediction equations for cardiovascular outcomes among patients with type 2 diabetes in real-world settings: a cross-institutional study using common data model approach.

OBJECTIVE: To adapt risk prediction equations for myocardial infarction (MI), stroke, and heart failure (HF) among patients with type 2 diabetes in real-world settings using cross-institutional electronic health records (EHRs) in Taiwan. METHODS: The EHRs from two medical centers, National Cheng Kung University Hospital (NCKUH; 11,740 patients) and National Taiwan University Hospital (NTUH; 20,313 patients), were analyzed using the common data model approach. Risk equations for MI, stroke, and HF from UKPDS-OM2, RECODe, and CHIME models were adapted for external validation and recalibration. External validation was assessed by (1) discrimination, evaluated by the area under the receiver operating characteristic curve (AUROC) and (2) calibration, evaluated by calibration slopes and intercepts and the Greenwood-Nam-D'Agostino (GND) test. Recalibration was conducted for unsatisfactory calibration (p-value of GND test < 0.05) by adjusting the baseline hazards of original equations to address variations in patients' cardiovascular risks across institutions. RESULTS: The CHIME risk equations had acceptable discrimination (AUROC: 0.71-0.79) and better calibration than that for UKPDS-OM2 and RECODe, although the calibration remained unsatisfactory. After recalibration, the calibration slopes/intercepts of the CHIME-MI, CHIME-stroke, and CHIME-HF risk equations were 0.9848/- 0.0008, 1.1003/- 0.0046, and 0.9436/0.0063 in the NCKUH population and 1.1060/- 0.0011, 0.8714/0.0030, and 1.0476/- 0.0016 in the NTUH population, respectively. All the recalibrated risk equations showed satisfactory calibration (p-values of GND tests ≥ 0.05). CONCLUSIONS: We provide valid risk prediction equations for MI, stroke, and HF outcomes in Taiwanese type 2 diabetes populations. A framework for adapting risk equations across institutions is also proposed.

Kinetic investigation on the catalytic pyrolysis of plastic fractions of waste electrical and electronic equipment (WEEE): A mathematical deconvolution approach.

Waste electrical and electronic equipment (WEEE) has become a critical environmental problem. Catalytic pyrolysis is an ideal technique to treat and convert the plastic fraction of WEEE into chemicals and fuels. Unfortunately, research using real WEEE remains relatively limited. Furthermore, the complexity of WEEE complicates the analysis of its pyrolytic kinetics. This study applied the Fraser-Suzuki mathematical deconvolution method to obtain the pseudo reactions of the thermal degradation of two types of WEEE, using four different catalysts (Al2O3, HBeta, HZSM-5, and TiO2) or without a catalyst. The main contributor(s) to each pseudo reaction were identified by comparing them with the pyrolysis results of the pure plastics in WEEE. The nth order model was then applied to estimate the kinetic parameters of the obtained pseudo reactions. In the low-grade electronics pyrolysis, the pseudo-1 reaction using TiO2 as a catalyst achieved the lowest activation energy of 92.10 kJ/mol, while the pseudo-2 reaction using HZSM-5 resulted in the lowest activation energy of 101.35 kJ/mol among the four catalytic cases. For medium-grade electronics, pseudo-3 and pseudo-4 were the main reactions for thermal degradation, with HZSM-5 and TiO2 yielding the lowest pyrolytic activation energies of 75.24 and 226.39 kJ/mol, respectively. This effort will play a crucial role in comprehending the pyrolysis kinetic mechanism of WEEE and propelling this technology toward a brighter future.