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.

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.

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.

Predicting high-risk pre-capillary pulmonary hypertension: an echocardiographic multiparameter scoring index.

BACKGROUND: The risk stratification of pulmonary arterial hypertension proposed by the European Society of Cardiology /European Respiratory Society guidelines in 2015 and 2022 included two to three echocardiographic indicators. However, the specific value of echocardiography in risk stratification of pre-capillary pulmonary hypertension (pcPH) has not been efficiently demonstrated. Given the complex geometry of the right ventricular (RV) and influencing factors of echocardiographic parameter, there is no single echocardiographic parameter that reliably informs about PH status. We hypothesize that a multi-parameter comprehensive index can more accurately evaluate the severity of the pcPH. The purpose of this study was to develop and validate an echocardiographic risk score model to better assist clinical identifying high risk of pcPH during initial diagnosis and follow-up. METHODS: We studied 197 consecutive patients with pcPH. A multivariable echocardiographic model was constructed to predict the high risk of pcPH in the training set. Points were assigned to significant risk factors in the final model based on ß-coefficients. We validated the model internally and externally. RESULTS: The echocardiographic score was constructed by multivariable logistic regression, which showed that pericardial effusion, right atrial (RA) area, RV outflow tract proximal diameter (RVOT-Prox), the velocity time integral of the right ventricular outflow tract (TVIRVOT) and S' were predictors of high risk of pcPH. The area under curve (AUC) of the training set of the scoring model was 0.882 (95%CI: 0.809-0.956, p < 0.0001). External validation was tested in a test dataset of 77 patients. The AUC of the external validation set was 0.852. A 10-point score risk score was generated, with scores ranging from 0 to 10 in the training cohort. The estimate risk of high risk of pcPH ranged from 25.1 to 94.6%. CONCLUSIONS: The echocardiographic risk score using five echocardiographic parameters could be comprehensive and useful to predict the high risk of pcPH for initial assessment and follow-up.

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.

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.

Shallow groundwater table fluctuations promote the accumulation and loss of phosphorus from surface soil to deeper soil in croplands around plateau lakes in Southwest China.

The continuous excessive application of phosphorus (P) fertilizers in intensive agricultural production leads to a large accumulation of P in surface soils, increasing the risk of soil P loss by runoff and leaching. However, there are few studies on the accumulation and loss of P from surface soil to deep soil profiles driven by shallow groundwater table (SGT) fluctuations. This study used the intensive cropland around 7 plateau lakes in Yunnan Province as an example and conducted in situ monitoring of P storage in the soil profile and SGT during the rainy season (RS) and dry season (DS) as well as simulation experiments on soil P loss. The aim was to study the spatiotemporal variation in P accumulation in the soil profile of cropland driven by SGT fluctuations in the RS and DS and estimate the P loss in the soil profile driven by SGT fluctuations. The results showed that fluctuations in the SGT promoted P accumulation from the surface soil to deeper soil. The proportions of P stored in various forms in the 30-60 cm and 60-100 cm soil layers in the RS were greater than those in the DS, while the average proportion in the 0-30 cm soil layer in the DS was as high as 48%. Compared with those in the DS, the maximum decreases in the proportion of P stored as TP and Olsen-P in the 0-100 cm soil layer in the RS were 16% and 58%, respectively, due to the rise in the SGT (SGT <30 cm), while the soil TP storage decreased by only 1% when the SGT was maintained at 60-100 cm. The critical thresholds for soil Olsen-P and TP gradually decreased with increasing soil depth, and the risk of P loss in deeper soil increased. The loss of soil P was increased by fluctuations in the SGT. Based on the cropland area around the 7 plateau lakes, P storage, and SGT fluctuations, the average loss intensity and loss amount of TP in the 0-100 cm soil layer around the 7 plateau lakes were estimated to be 25 kg/ha and 56 t, respectively. Therefore, reducing exogenous P inputs, improving soil endogenous P utilization efficiency and maintaining deep soil P retention are the basic strategies for preventing and controlling P accumulation and loss in deep soil caused by SGT fluctuations.

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.

[Modular pharmacology: research progress and development of analysis platform].

Based on the systematic deconstruction of multi-dimensional and multi-target biological networks, modular pharmacology explains the complex mechanism of diseases and the interactions of multi-target drugs. It has made progress in the fields of pathogenesis of disease, biological basis of disease and traditional Chinese medicine(TCM) syndrome, pharmacological mechanism of multi-target herbs, compatibility of formulas, and discovery of new drug of TCM compound. However, the complexity of multi-omics data and biological networks brings challenges to the modular deconstruction and analysis of the drug networks. Here, we constructed the "Computing Platform for Modular Pharmacology" online analysis system, which can implement the function of network construction, module identification, module discriminant analysis, hub-module analysis, intra-module and inter-module relationship analysis, and topological visualization of network based on quantitative expression profiles and protein-protein interaction(PPI) data. This tool provides a powerful tool for the research on complex diseases and multi-target drug mechanisms by means of modular pharmacology. The platform may have broad range of application in disease modular identification and correlation mechanism, interpretation of scientific principles of TCM, analysis of complex mechanisms of TCM and formulas, and discovery of multi-target drugs.

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.

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.

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.

[Effect of Fallow on Nitrogen Accumulation in Soil Profile and Shallow Groundwater in Cropland Around Fuxian Lake].

Soil nitrogen accumulation in cropland and groundwater nitrogen pollution can be effectively alleviated by reducing exogenous nitrogen input, and fallow is an important measure for reducing exogenous nitrogen input. To explore the effects of fallow on nitrogen accumulation in the soil profile and shallow groundwater, the soil profile and shallow groundwater in cropland around Fuxian Lake were selected as research objects. The changes in nitrogen accumulation in the 0-100 cm soil profile and nitrogen concentration in shallow groundwater before (December 2017) and after (August 2020 and April 2021) fallow and their relationships were analyzed. The results showed that the content and storage of nitrogen in soil profiles were significantly reduced by fallow, and the contents of TN, ON, DTN, NO3--N, and NH4+-N in 0-30, 30-60, and 60-100 cm soil profiles after fallow decreased by 18.4 %-36.5 %, 16.1 %-26.8 %, 54.0 %-130.2 %, 59.5 %-90.8 %, and 60.1 %-110.6 %, respectively. The storages of TN, ON, DTN, NO3--N, and NH4+-N in 0-100 cm soil profiles before fallow were (17.20 ±0.97) t·hm-2, (15.50 ±1.23) t·hm-2, (0.68 ±0.06) t·hm-2, (266.8 ±31.17) kg·hm-2, and (18.7 ±3.04) kg·hm-2, respectively. However, their storages after fallow decreased by 25.5 %, 23.3 %, 44.7 %, 80.1 %, and 59.9 %, respectively. Fallow also changed the concentration and composition of different forms of nitrogen in shallow groundwater. The concentrations of TN, ON, NO3--N, and NH4+-N in groundwater after fallow decreased by 88.4 %, 82.7 %, 92.1 %, and 65.8 %, respectively, and ON/TN and NH4+-N/TN increased from 26 % and 6 % before fallow to 39 % and 17 % after fallow, respectively, whereas NO3--N/TN decreased from 61 % before fallow to 41 % after fallow. Changes in nitrogen concentrations and their forms in groundwater were closely related to DTN, NO3--N, and NH4+-N in the soil profile and pH, ORP, and DO in groundwater before and after fallow. Our study highlights that fallow effectively reduced nitrogen accumulation in cropland soil profiles, further alleviating nitrogen pollution in shallow groundwater, and was conducive to preventing the deterioration of water quality in plateau lakes.

Rapid reconstitution of ubiquitinated nucleosome using a non-denatured histone octamer ubiquitylation approach.

BACKGROUND: Histone ubiquitination modification is emerging as a critical epigenetic mechanism involved in a range of biological processes. In vitro reconstitution of ubiquitinated nucleosomes is pivotal for elucidating the influence of histone ubiquitination on chromatin dynamics. RESULTS: In this study, we introduce a Non-Denatured Histone Octamer Ubiquitylation (NDHOU) approach for generating ubiquitin or ubiquitin-like modified histone octamers. The method entails the co-expression and purification of histone octamers, followed by their chemical cross-linking to ubiquitin using 1,3-dibromoacetone. We demonstrate that nucleosomes reconstituted with these octamers display a high degree of homogeneity, rendering them highly compatible with in vitro biochemical assays. These ubiquitinated nucleosomes mimic physiological substrates in function and structure. Additionally, we have extended this method to cross-linking various histone octamers and three types of ubiquitin-like proteins. CONCLUSIONS: Overall, our findings offer an efficient strategy for producing ubiquitinated nucleosomes, advancing biochemical and biophysical studies in the field of chromatin biology.

Effectiveness of exercise programs to reduce low back pain among nurses and nursing assistants: A systematic review and meta-analysis.

INTRODUCTION: Nurses have a high prevalence of low back pain due to ergonomic hazards in healthcare workplaces. While exercise programs have been suggested as an intervention strategy, the effectiveness of low back pain programs has been inconsistent in the research literature. The purpose of study is to determine the effect of exercise programs to reduce low back pain among nursing staff. METHODS: A systematic review and meta-analysis was conducted with five databases and systematically searched. Following the PRISMA guidelines, included studies evaluated low back pain relief among nurses or nursing assistants and described the exercise program. Two reviewers independently appraised, extracted, and synthesized all available studies. The study protocol was registered in PROSPERO (CRD42022359511). RESULTS: A total of 296 articles with 1,355 nursing staff from nine countries were obtained. Nine randomized controlled trials with a moderate to low risk of bias quality were included. Exercise programs had a small but significant effect on low back pain of nursing staff (SMD = -0.48; 95% CI = -0.76 to -0.19; p = 0.03, I2 = 62%, p = 0.001). A subgroup analysis of nurses and nursing assistants showed moderate and small effects, respectively (I2 = 0% p < 0.0001, SMD -0.73 CI 95% [-0.97 to -0.48], p = 0.76, and I2 = 0% p = 0.002, SMD -0.23 CI 95% [-0.38 to -0.08], p < 0.88). Exercise for back and trunk exhibited a moderate effect on low back pain (SMD -0.56 CI 95% [-0.86 to -0.25], p = 0.01, I2 = 66%, p < 0.0004). A subgroup analysis comparing age, under 40 years old revealed a moderate effect size (SMD = -0.59; 95% CI = -0.83to -0.35; p = 0.06; I2 = 64%, p < 0.0001). CONCLUSIONS: Exercise programs are an effective treatment to reduce low back pain in nurses and nursing assistants, especially among younger staff. PRACTICAL APPLICATION: Back and trunk exercise programs should be recommended for nursing staff with low back pain.

Effects of methylation and transcription factor YY1 on ID2 expression in non-small cell lung carcinoma cells.

The inhibitor of DNA-binding 2 (ID2) plays a major role in tumor dedifferentiation in non-small cell lung cancer (NSCLC). Studies have indicated an inverse correlation between ID2 expression and NSCLC cell invasiveness. However, the mechanisms through which ID2 activation is regulated are currently unclear. We overexpressed ID2 in H1299 cells and extensively characterized their cellular behaviors. By employing a serial deletion approach combined with a reporter assay, we pinpointed the basal promoter region of ID2. We also examined the DNA methylation status of the ID2 promoter to elucidate the epigenetic mechanisms driving ID2 regulation. Our results revealed that ID2 overexpression effectively inhibited the migration, invasion, proliferation, and colony formation abilities of H1299 cells. The region from -243 to +202 played a major role in driving the transcriptional activity of ID2. Sequence analysis results indicated that the transcription factor Yin Yang 1 (YY1) might be crucial in the regulation of ID2 expression. The ectopically expressed YY1 activated both the expression levels of ID2 and the transcriptional activity of the ID2 promoter, potentially contributing to its repressive activity on cancer cell growth. Furthermore, site-directed mutagenesis and chromatin immunoprecipitation assays revealed that YY1 may target the -120 and -76 sites of the ID2 promoter, thereby activating its transcriptional activity. The ID2 promoter regions were also fully methylated in CL1-5 cells, and the methylation level was correlated with the expression levels of the ID2 promoter. Moreover, the YY1-induced suppression of colony formation was counteracted by ID2 knockdown, which suggests that YY1 represses cell colony growth through the regulation of ID2. Our results indicate that YY1 plays a role in transactivating ID2 expression and might also contribute to the repression of colony growth through the regulation of ID2.