Molecular Cloning, Tissue Distribution, and Pharmacological Characterization of GPR84 in Grass Carp (Ctenopharyngodon Idella).

The G-protein-coupled receptor GPR84, activated by medium-chain fatty acids, primarily expressed in macrophages and microglia, is involved in inflammatory responses and retinal development in mammals and amphibians. However, our understanding of its structure, function, tissue expression, and signaling pathways in fish is limited. In this study, we cloned and characterized the coding sequence of GPR84 (ciGPR84) in grass carp. A phylogenetic analysis revealed its close relationship with bony fishes. High expression levels of GPR84 were observed in the liver and spleen. The transfection of HEK293T cells with ciGPR84 demonstrated its responsiveness to medium-chain fatty acids and diindolylmethane (DIM). Capric acid, undecanoic acid, and lauric acid activated ERK and inhibited cAMP signaling. Lauric acid showed the highest efficiency in activating the ERK pathway, while capric acid was the most effective in inhibiting cAMP signaling. Notably, DIM did not activate GPR84 in grass carp, unlike in mammals. These findings provide valuable insights for mitigating chronic inflammation in grass carp farming and warrant further exploration of the role of medium-chain fatty acids in inflammation regulation in this species.

Identification of Mixtures of Two Types of Body Fluids Using the Multiplex Methylation System and Random Forest Models.

OBJECTIVE: Body fluid mixtures are complex biological samples that frequently occur in crime scenes, and can provide important clues for criminal case analysis. DNA methylation assay has been applied in the identification of human body fluids, and has exhibited excellent performance in predicting single-source body fluids. The present study aims to develop a methylation SNaPshot multiplex system for body fluid identification, and accurately predict the mixture samples. In addition, the value of DNA methylation in the prediction of body fluid mixtures was further explored. METHODS: In the present study, 420 samples of body fluid mixtures and 250 samples of single body fluids were tested using an optimized multiplex methylation system. Each kind of body fluid sample presented the specific methylation profiles of the 10 markers. RESULTS: Significant differences in methylation levels were observed between the mixtures and single body fluids. For all kinds of mixtures, the Spearman's correlation analysis revealed a significantly strong correlation between the methylation levels and component proportions (1:20, 1:10, 1:5, 1:1, 5:1, 10:1 and 20:1). Two random forest classification models were trained for the prediction of mixture types and the prediction of the mixture proportion of 2 components, based on the methylation levels of 10 markers. For the mixture prediction, Model-1 presented outstanding prediction accuracy, which reached up to 99.3% in 427 training samples, and had a remarkable accuracy of 100% in 243 independent test samples. For the mixture proportion prediction, Model-2 demonstrated an excellent accuracy of 98.8% in 252 training samples, and 98.2% in 168 independent test samples. The total prediction accuracy reached 99.3% for body fluid mixtures and 98.6% for the mixture proportions. CONCLUSION: These results indicate the excellent capability and powerful value of the multiplex methylation system in the identification of forensic body fluid mixtures.

Association of cardiovascular disease with health-related quality of life among older women with early-stage breast cancer undergoing adjuvant endocrine therapy.

INTRODUCTION: Due to the improved overall survival and life expectancy of older women with breast cancer, cardiovascular disease (CVD) arose as the primary cause of non-cancer-related deaths in this population. Therefore, assessing the health-related quality of life (HRQoL) of breast cancer patients with comorbid CVD is becoming increasingly vital. Our study aimed to evaluate the association between comorbid CVD and HRQoL among older women with early-stage breast cancer who are receiving adjuvant endocrine therapy (AET) in the United States. MATERIALS AND METHODS: We conducted a retrospective cohort study using the 2006-2017 Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey data. We identified female patients over the age of 65 who were diagnosed with stage I-III hormone receptor-positive breast cancer and treated with AET. HRQoL was assessed by the physical and mental component summary (PCS & MCS) in the health survey. CVD was defined as a history of acute myocardial infarction (AMI), congestive heart failure (CHF), angina, stroke, or other heart-related conditions. We performed multivariate linear regression models while controlling for covariates. RESULTS: Among 3,904 older women, a history of CHF [ß = -1.97, p = 0.025], stroke [ß = -3.00, p < 0.010], or other heart-related condition [ß = -1.10, p = 0.046] was significantly associated with lower PCS. However, no significant differences in PCS scores were found between women with a history of AMI or angina and those without these conditions. Having a history of CHF [ß = -1.72, p = 0.033] or stroke [ß = -1.48, p = 0.038] was significantly associated with lower MCS, whereas a history of angina, AMI, or other heart conditions was not associated with significant differences in MCS. Our study did not observe any significant differences in PCS and MCS between the two types AETs. DISCUSSION: The study found that older women with early-stage breast cancer who were being treated with AETs had a lower HRQoL if they had a history of CHF or stroke. These comorbidities were identified as strong predictors for decreased HRQoL. The findings highlight the significance of managing cardiovascular diseases in such patients for better HRQoL while they receive AET treatment.

Trinuclear Re(I)-Coordinated Organic Cage as the Supramolecular Photocatalyst for Visible-Light-Driven CO2 Reduction.

Photocatalytic reduction of excess CO2 in the atmosphere to value-added chemicals by visible light can be an effective solution to fuel shortage and global warming. Considering these issues, we designed and successfully synthesized a trinuclear Re(I)-coordinated organic cage (Re-C4R) as the supramolecular photocatalyst. Photophysical, electrochemical properties, and photocatalytic performance comparison of Re-C4R and its mononuclear analogue Re-bpy are discussed in detail. Notably, the covalent linkage of three Re(I) subunits in Re-C4R leads to TONCO = 691 (per Re(I) site in 4 h) more than three times as much as TONCO = 208 of Re-bpy. Compared to Re-bpy, higher current enhancement in the control CV experiments under CO2 was observed for Re-C4R. CO2 adsorption process can be promoted because of the cryptand structure and multiple amine groups of Re-C4R. Moreover, decay lifetimes of Re-C4R are shorter than those of Re-bpy in the ultrafast transient absorption (TA) and photoluminescence (PL) decay spectra, indicating that the trinuclear cryptate structure of Re-C4R could facilitate electron transfer efficiency during CO2 reduction.

One/Two-Photon-Excited ESIPT-Attributed Coordination Polymers with Wide Temperature Range and Color-Tunable Long Persistent Luminescence.

The multiple metastable excited states provided by excited-state intramolecular proton transfer (ESIPT) molecules are beneficial to bring temperature-dependent and color-tunable long persistent luminescence (LPL). Meanwhile, ESIPT molecules are intrinsically suitable to be modulated as D-π-A structure to obtain both one/two-photon excitation and LPL emission simultaneously. Herein, we report the rational design of a dynamic CdII coordination polymer (LIFM-106) from ESIPT ligand to achieve the above goals. By comparing LIFM-106 with the counterparts, we established a temperature-regulated competitive relationship between singlet excimer and triplet LPL emission. The optimization of ligand aggregation mode effectively boost the competitiveness of the latter. In result, LIFM-106 shows outstanding one/two-photon excited LPL performance with wide temperature range (100-380 K) and tunable color (green to red). The multichannel radiation process was further elucidated by transient absorption and theoretical calculations, benefiting for the application in anti-counterfeiting systems.

Use of machine learning to predict bladder cancer survival outcomes: a systematic literature review.

INTRODUCTION: The objective of this systematic review is to summarize the use of machine learning (ML) in predicting overall survival (OS) in patients with bladder cancer. METHODS: Search terms for bladder cancer, ML algorithms, and mortality were used to identify studies in PubMed and Web of Science as of February 2022. Notable inclusion/exclusion criteria contained the inclusion of studies that utilized patient-level datasets and exclusion of primary gene expression-related dataset studies. Study quality and bias were assessed using the International Journal of Medical Informatics (IJMEDI) checklist. RESULTS: Of the 14 included studies, the most common algorithms were artificial neural networks (n = 8) and logistic regression (n = 4). Nine articles described missing data handling, with five articles removing patients with missing data entirely. With respect to feature selection, the most common sociodemographic variables were age (n = 9), gender (n = 9), and smoking status (n = 3), with clinical variables most commonly including tumor stage (n = 8), grade (n = 7), and lymph node involvement (n = 6). Most studies (n = 10) were of medium IJMEDI quality, with common areas of improvement being the descriptions of data preparation and deployment. CONCLUSIONS: ML holds promise for optimizing bladder cancer care through accurate OS predictions, but challenges related to data processing, feature selection, and data source quality must be resolved to develop robust models. While this review is limited by its inability to compare models across studies, this systematic review will inform decision-making by various stakeholders to improve understanding of ML-based OS prediction in bladder cancer and foster interpretability of future models.

An analysis type known as machine learning has recently become popular to predict survival in bladder cancer patients. However, there is debate on how to best use this method, as well as how to report the results of studies. This review looks at recently published machine learning studies, comparing various model details. Most studies found used hospital data, were clear about model factors, and used a model type called artificial neural networks. While these studies may be better at prediction compared to previous methods, there are consistency and clarity issues. Future studies should ensure that models are explainable and relevant to healthcare leaders.

The Contribution of Epigenetics to Evolutionary Adaptation in Zingiber kawagoii Hayata (Zingiberaceae) Endemic to Taiwan.

We epigenotyped 211 individuals from 17 Zingiber kawagoii populations using methylation-sensitive amplification polymorphism (MSAP) and investigated the associations of methylated (mMSAP) and unmethylated (uMSAP) loci with 16 environmental variables. Data regarding genetic variation based on amplified fragment length polymorphism (AFLP) were obtained from an earlier study. We found a significant positive correlation between genetic and epigenetic variation. Significantly higher mean mMSAP and uMSAP uHE (unbiased expected heterozygosity: 0.223 and 0.131, respectively, p < 0.001) per locus than that estimated based on AFLP (uHE = 0.104) were found. Genome scans detected 10 mMSAP and 9 uMSAP FST outliers associated with various environmental variables. A significant linear fit for 11 and 12 environmental variables with outlier mMSAP and uMSAP ordination, respectively, generated using full model redundancy analysis (RDA) was found. When conditioned on geography, partial RDA revealed that five and six environmental variables, respectively, were the most important variables influencing outlier mMSAP and uMSAP variation. We found higher genetic (average FST = 0.298) than epigenetic (mMSAP and uMSAP average FST = 0.044 and 0.106, respectively) differentiation and higher genetic isolation-by-distance (IBD) than epigenetic IBD. Strong epigenetic isolation-by-environment (IBE) was found, particularly based on the outlier data, controlling either for geography (mMSAP and uMSAP ßE = 0.128 and 0.132, respectively, p = 0.001) or for genetic structure (mMSAP and uMSAP ßE = 0.105 and 0.136, respectively, p = 0.001). Our results suggest that epigenetic variants can be substrates for natural selection linked to environmental variables and complement genetic changes in the adaptive evolution of Z. kawagoii populations.

Interplay of Dual-Proton Transfer Relay to Achieve Full-Color Panel Luminescence in Excited-State Intramolecular Proton Transfer (ESIPT) Fluorophores.

A new design was applied for the facile synthesis of pure organic photoluminescent molecules with dual excited-state intramolecular proton transfer (ESIPT) sites. In this novel class of emitters, full-color panel emission from blue, green, and yellow to red, including white light, can be achieved in different solvents as modulated by the enol-keto(1st)-keto(2nd) tautomer emissions. A comprehensive transient photophysical study verifies that keto(1st) and keto(2nd) have a precursor (<0.8 ps)-successor (∼20 ps)-relayed absorbance relationship, and then a fast equilibrium between the two is established, resulting in dual emissions in the nanosecond scale (∼1900 ps). Through the research on copper ions' selective PL response, the dual-ESIPT mechanism was further verified; in addition, the study of solid-state PL changes upon the stimulus of organic vapor manifests the potential application sensitivity of the molecules as dual-ESIPT sensors. Theoretical results including reaction potential energy surface analyses manifest the fact that dual-proton transfer goes along a sequential route with a smaller energy barrier, firmly supporting the experimental results. An intrinsic system that undergoes intramolecular double proton relayed transfer is thus established for the achievement of much broadened optical responses and full-color display, providing reference for the design and application of advanced dual-ESIPT optical materials.

Risk of Cardiovascular Events with Cyclin-Dependent Kinases 4 and 6 (CDK 4/6) Inhibitors among Patients with Advanced Breast Cancer: A Systematic Review and Network Meta-Analysis.

Background: Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors have shown promising survival outcomes with additional treatments to the traditional endocrine therapy (ET) in patients with hormone receptor-positive (HR-positive) and human epidermal growth factor receptor type 2 negative (HER2-negative) advanced breast cancer (aBC). However, the head-to-head cardiovascular safety profile of these three agents (palbociclib, ribociclib, and abemaciclib) remains unclear. We summarized the incidence of major adverse cardiovascular events (MACE) and hypertension associated with the use of CDK4/6 inhibitor in randomized control trials (RCTs) and compared the risks of MACE and hypertension through network-meta analysis (NMA). Methods: A systematic search through PubMed and Cochrane Library was performed to identify phase III RCTs reporting cardiovascular safety data of CDK4/6 inhibitors in patients with aBC. We qualitatively synthesized the incidence of MACE and hypertension associated with CDK4/6 inhibitor use within on-treatment or placebo-controlled duration. A Bayesian NMA with random-effects models was performed, and pairwise comparisons between treatment options were presented by odds ratio (OR). The probability of each treatment arm's relative ranking was reported using surface under the cumulative ranking curve (SUCRA) scores. A sensitivity analysis was conducted using the Mantel-Haenszel (MH) method. Results: Nine RCTs with four unique treatment arms and event(s) in at least one arm were included in the NMA. A total of 5218 patients were analyzed for MACE outcomes. The overall incidence of MACE in the CDK4/6 inhibitors+ET arm was 0.8%, while the endocrine therapy alone group was 0.4%. Abemaciclib+ET ranked the best in reducing the risk of MACE (SUCRA = 0.90) as compared to ET alone (SUCRA = 0.67, OR = 0.45, 95% credible interval (CI) = 0.07-2.82), palbociclib+ET (SUCRA = 0.25, OR = 0.09, 95% CI = 0.00-2.39) and ribociclib+ET (SUCRA = 0.17, OR = 0.08, 95% CI = 0.00-1.18). The findings were similar in the MH network. However, abemaciclib+ET (OR = 0.11; 95% CI = 0.02-0.81) had a significantly lower risk of MACE than ribociclib+ET in the MH network. No statistically significant differences in hypertension were shown among all comparisons. Conclusions: Abemaciclib+ET may have a lower risk of MACE for the treatment of aBC, while palbociclib+ET may reduce the risk of hypertension in this population. Our findings suggest a comparative cardiovascular safety trend among the three CDK4/6 inhibitors, but further research on direct comparisons is needed to guide treatment choice.

Pattern of Adaptive Divergence in Zingiber kawagoii Hayata (Zingiberaceae) along a Narrow Latitudinal Range.

Ecological and evolutionary processes linking adaptation to environment are related to species' range shifts. In this study, we employed amplified-fragment-length-polymorphism-based genome scan methods to identify candidate loci among Zingiber kawagoii populations inhabiting varying environments distributed at low to middle elevations (143-1488 m) in a narrow latitudinal range (between 21.90 and 25.30° N). Here, we show evidence of selection driving the divergence of Z. kawagoii. Twenty-six FST outliers were detected, which were significantly correlated with various environmental variables. The allele frequencies of nine FST outliers were either positively or negatively correlated with the population mean FST. Using several independent approaches, we found environmental variables act in a combinatorial fashion, best explaining outlier genetic variation. Nonetheless, we found that adaptive divergence was affected mostly by annual temperature range, and it is significantly positively correlated with latitude and significantly negatively correlated with the population mean FST. This study addresses a latitudinal pattern of changes in annual temperature range (which ranged from 13.8 °C in the Lanyu population to 18.5 °C in the Wulai population) and emphasizes the pattern of latitudinal population divergence closely linked to the allele frequencies of adaptive loci, acting in a narrow latitudinal range. Our results also indicate environmentally dependent local adaptation for both leading- and trailing-edge populations.

Detection of Abnormal Spontaneous Brain Activity Patterns in Patients With Orbital Fractures Using Fractional Amplitude of Low Frequency Fluctuation.

Background: To date, no in-depth study has been conducted on the intrinsic pathological relationship between altered brain activity and related behavioral changes in patients with orbital fracture (OF). Purpose: The present research aimed to explore the potential functional network cerebrum activities in patients with OF using resting state functional magnetic resonance imaging-fractional amplitude of low-frequency fluctuation (rsfMRI-fALFF). This technique can reveal dynamic functional changes in specific cerebrum areas. Methods: Twenty patients with OF and 20 healthy controls (HCs) were included, closely matched in terms of gender, age, weight, and education level. To record spontaneous cerebral activity changes, the rsfMRI-fALFF tool was applied. Receiver operating characteristic (ROC) curves and Pearson's correlation analysis were used to analyze mean fALFF values in specific cerebrum regions and to explore changes of behavioral changes in patients with OF. The Hospital Depression and Anxiety scale was applied to reveal the relationship between emotional states and fALFF values of the right superior temporal gyrus in patients with OF. Results: In comparison with HCs, significantly lower fALFF values were detected in the left anterior cingulate gyrus (LACG) and right superior temporal gyrus (RSTG) in patients with OF. ROC curve analysis showed excellent accuracy. The mean fALFF values of the RSTG negatively correlated with the depression score as well as the anxiety score. Conclusion: The finding of abnormal spontaneous activities in cerebral regions may contribute to more comprehensive understanding of the potential neural network changes in patients with OF. The changes of fALFF value in patients with OF may help to gauge their emotional changes and clinical recovery levels.

Sphingosine-1-Phosphate Protects Against the Development of Cardiac Remodeling via Sphingosine Kinase 2 and the S1PR2/ERK Pathway.

OBJECTIVE: Cardiac remodeling is a common pathological change in various cardiovascular diseases and can ultimately result in heart failure. Thus, there is an urgent need for more effective strategies to aid in cardiac protection. Our previous work found that sphingosine-1-phosphate (S1P) could ameliorate cardiac hypertrophy. In this study, we aimed to investigate whether S1P could prevent cardiac fibrosis and the associated mechanisms in cardiac remodeling. METHODS: Eight-week-old male C57BL/6 mice were randomly divided into a sham, transverse aortic constriction (TAC) or a TAC+S1P treatment group. RESULTS: We found that S1P treatment improved cardiac function in TAC mice and that the cardiac fibrosis ratio in the TAC+S1P group was significantly lower and was accompanied by a decrease in α-smooth muscle actin (α-SMA) and collagen type I (COL I) expression compared with the TAC group. We also found that one of the key S1P enzymes, sphingosine kinase 2 (SphK2), which was mainly distributed in cytoblasts, was downregulated in the cardiac remodeling case and recovered after S1P treatment in vivo and in vitro. In addition, our in vitro results showed that S1P treatment activated extracellular regulated protein kinases (ERK) phosphorylation mainly through the S1P receptor 2 (S1PR2) and spurred p-ERK transposition from the cytoplasm to cytoblast in H9c2 cells exposed to phenylephrine. CONCLUSION: These findings suggest that SphK2 and the S1PR2/ERK pathway may participate in the anti-remodeling effect of S1P on the heart. This work therefore uncovers a novel potential therapy for the prevention of cardiac remodeling.

Patterns and predictors of oral antipsychotic prescribing in adult patients with schizophrenia.

Background: Evidence increasingly suggests minimal differences in efficacy between oral antipsychotics for the pharmacologic treatment of schizophrenia. As a result, newer treatment guidelines avoid an algorithmic approach to antipsychotic selection and recommend treatment be determined on a case-by-case basis. Objective: To determine patterns and predictors of oral antipsychotic prescribing for adults diagnosed with schizophrenia. Methods: This is a retrospective, cross-sectional study using data from the National Ambulatory Medical Survey (NAMCS) from 2005 to 2016 and 2018. Treatment options were defined as a first-generation antipsychotic (FGA), second-generation antipsychotic (SGA), or no antipsychotic. Multivariable logistic regression analysis was conducted to identify predictors of antipsychotic treatment, adjusting for predisposing, enabling, and need factors. Results: The final study sample consisted of visits by 38,403 adults (unweighted n = 1932; age ≥ 18) diagnosed with schizophrenia in the United States. Risperidone, olanzapine, and quetiapine were the most prescribed antipsychotics. Patients ≥65 years old were half as likely to be prescribed an SGA versus no antipsychotic (OR 0.44, 95% CI [0.31, 0.61]). Patients with a higher number of chronic conditions also had lower odds of being prescribed an SGA or FGA versus no antipsychotic (OR 0.98 [0.97, 0.99]; OR [0.96 [0.96, 0.99]), while patients prescribed a higher number of medications had higher odds of being prescribed an SGA versus no antipsychotic (OR 1.2, 95% CI [1.1, 1.4]). Conclusions: Multiple factors were associated with prescribing an SGA or FGA versus no antipsychotic, but no factors were associated with prescribing an SGA versus FGA. Future studies are needed to determine the reasoning behind differences in antipsychotic prescribing.

A systematic review of economic evaluations of tyrosine kinase inhibitors for non-small cell lung cancer (NSCLC).

INTRODUCTION: Although tyrosine kinase inhibitors (TKIs) have improved the efficacy of treatment for non-small cell lung cancer (NSCLC), the accessibility of TKIs is limited due to high costs. Despite the critical role of the cost-effectiveness of TKIs on decision-making, no systematic reviews have compared the cost-effectiveness of comparable TKIs. Therefore, we systemically reviewed the economic evaluation studies on various TKIs for NSCLC. AREAS COVERED: We searched PubMed and the Cochran Library to identify the published economic evaluation studies of TKIs in NSCLC patients that were published by January 2022. All of the included studies (n = 38) evaluated the cost-effectiveness of epidermal growth factor receptor (EGFR)-TKIs (n = 29) or anaplastic lymphocyte kinase (ALK)-TKIs (n = 9). The cost-effectiveness results were reported as the incremental cost-effectiveness ratio per quality-adjusted life-year, except for three studies. EXPERT OPINION: We found that the economic evaluation studies of the first and second generation of EGFR-TKIs and ALK-TKIs varied by the country and study settings, such as comparator and input parameters. In 12 studies, osimertinib (EGFR-TKI) was not cost-effective compared to other first/second EGFR-TKIs, regardless of the study settings. More evidence can be provided about cost-effectiveness of the third-generation TKIs in future research.

Adaptive Divergence without Distinct Species Relationships Indicate Early Stage Ecological Speciation in Species of the Rhododendronpseudochrysanthum Complex Endemic to Taiwan.

The testing association of environmental variables with genetic and epigenetic variation could be crucial to deciphering the effects of environmental factors playing roles as selective drivers in ecological speciation. Although ecological speciation may occur in closely related species, species boundaries may not be established over a short evolutionary timescale. Here, we investigated the genetic and epigenetic variations using amplified fragment length polymorphism (AFLP) and methylation-sensitive amplification polymorphism (MSAP), respectively, and tested their associations with environmental variables in populations of four closely related species in the R. pseudochrysanthum complex. No distinctive species relationships were found using genetic clustering analyses, neighbor-joining tree, and neighbor-net tree based on the total AFLP variation, which is suggestive of the incomplete lineage sorting of ancestral variation. Nonetheless, strong isolation-by-environment and adaptive divergence were revealed, despite the significant isolation-by-distance. Annual mean temperature, elevation, normalized difference vegetation index, and annual total potential evapotranspiration were found to be the most important environmental variables explaining outlier genetic and epigenetic variations. Our results suggest that the four closely related species of the R. pseudochrysanthum complex share the polymorphism of their ancestor, but reproductive isolation due to ecological speciation can occur if local environmental divergence persists over time.

Relaxin inhibits renal fibrosis and the epithelial-to-mesenchymal transition via the Wnt/ß-catenin signaling pathway.

Renal fibrosis is a common characteristic and the final pathological mechanism of chronic kidney disease (CKD). Although CKD remains incurable, inhibition of renal fibrosis is beneficial to inhibit the CKD process. Relaxin alleviates renal fibrosis in some experimental models, but its mechanism remains unclear. In the following, we studied the regulatory effect of relaxin on epithelial-mesenchymal transition (EMT) after unilateral ureteral obstruction (UUO). Our results demonstrate that relaxin could downregulate Wnt/ß-catenin signaling and decrease EMT, thus protecting against loss of transporters in tubular epithelial cells (TECs) and abrogate renal interstitial fibrosis following UUO. We confirmed that relaxin can downregulate Wnt/ß-catenin signaling and decrease EMT in NRK52E, thus abrogating G2 cell cycle arrest in vitro experiments. Therefore, a novel mechanism by which relaxin is antifibrotic is that relaxin regulates the EMT program of TECs via Wnt/ß-catenin signaling pathway. The inhibition of EMT contributes to protecting the functional capabilities of TECs and promoting the regeneration of TECs.

Economic Burden of Chronic Comorbidities Among Community-Dwelling Older Adults With Dementia: A Propensity Score Matched National-Level Study.

OBJECTIVE: This study examined the extent to which chronic comorbidities contribute to excess health care expenditures between older adults with dementia and propensity score (PS)-matched nondementia controls. METHODS: This was a retrospective, cross-sectional, PS-matched case (dementia): control (nondementia) study of older adults (65 y or above) using alternative years data from pooled 2005 to 2015 Medical Expenditure Panel Surveys (MEPS). Chronic comorbidities were identified based on Clinical Classifications System or ICD-9-CM codes. Ordinary least squares regression was utilized to quantify the impact of chronic comorbidities on the excess expenditures with logarithmic transformation. Expenditures were expressed as 2019 US dollars. All analyses accounted for the complex survey design of MEPS. RESULTS: The mean yearly home health care expenditures were particularly higher among older adults with dementia and co-occurring anemia, eye disorders, hyperlipidemia, and hypertension compared with PS-matched controls. Ordinary least squares regression models revealed that home health care expenditures were 131% higher (ß=0.837, P <0.001) among older adults with dementia compared with matched nondementia controls before adjusting for chronic comorbidities. When additionally adjusting for chronic comorbidities, the percentage increase, while still significant ( P <0.001) decreased from 131% to 102%. CONCLUSIONS: The excess home health care expenditures were partially explained by chronic comorbidities among community-dwelling older adults with dementia.

[Randomized controlled trials of acupuncture and moxibustion in China in past 45-year (1975-2019): hotspots and trends].

By searching the randomized controlled trials (RCTs) of acupuncture and moxibustion from CNKI since its inception date to december 31 of 2019, the development status and hot trend of RCTs of acupuncture and moxibustion in China were summarized. The CiteSpace and VOSviewer software were used to perform keyword co-occurrence analysis, clustering analysis, time-zone analysis and citation-burst analysis, and visual map was drawn. As a result, a total of 60 995 articles were included, which were published in 1027 academic journals with 1787 keywords. The publication date was from 1975 to 2019. During the past 45 years, the publications of RCTs on acupuncture and moxibustion had shown an overall growth trend with characteristics of the times. The RCTs of manual acupuncture ranked the top, and its proportion of publications every 5 years was stable in the past 30 years. Since 1994, the hot words such as electroacupuncture, warming needling, auricular point sticking and various acupoint therapies had emerged; meanwhile, the spectrum of diseases had broadened, and an evolutionary trend corresponding to therapies and disease systems had been formed. In recent decade, the RCTs using moxibustion therapy have increased significantly, and the hot words such as "sub-health" "winter diseases being treated in summer" and "acupoint application/ moxibustion during the dog days" had indicated that acupuncture clinical research was further inclined to the field of chronic disease prevention and health services, which was in line with social development and the needs of the times.

An aniline trimer-based multifunctional sensor for colorimetric Fe3+, Cu2+ and Ag+ detection, and its complex for fluorescent sensing of L-tryptophan.

The detection of metal ions and amino acids by the aniline oligomer-based receptor has not been reported yet, to the best of our knowledge. In this study, an efficient multifunctional cation-amino acid sensor (CAS) with aniline moiety and chiral thiourea binding site was synthesized by the reaction of aniline trimer and (S)-(+)-1-phenyl ethyl isothiocyanate. CAS can sense Fe3+, Cu2+, Ag+ ions, and L-tryptophan. These results can be recognized by the naked eye. The appropriate pH range for the quantitative analysis of Fe3+, Cu2+, and Ag+ by CAS in DMSO/water (30 vol% water) was evaluated. The interaction between CCS and metal ions was analyzed by 1H NMR titration. The detection limits of CAS for the Cu2+, Ag+, and Fe3+ were 0.214, 0.099, and 0.147 µM, respectively. Moreover, the CASCu2+ complex can act as a turn-on fluorescence sensor for L-tryptophan. On the contrary, there is no response upon the addition of other amino acids, such as L-histidine, L-proline, L-phenylalanine, L-threonine, L-methionine, L-tyrosine, and L-cystine to CASCu2+ complex.

Correction: Role of Caveolin-1 in Atrial Fibrillation as an Anti-Fibrotic Signaling Molecule in Human Atrial Fibroblasts.

[This corrects the article DOI: 10.1371/journal.pone.0085144.].