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BackgroundAt present, the available evidence regarding the relationship between duration of phenoxybenzamine use and postoperative delirium is inadequate in suspected adrenal pheochromocytoma.ObjectiveTo understand how changes in the duration of phenoxybenzamine use may affect postoperative delirium. The secondary objective of this study is to explore how the duration of phenoxybenzamine use may jointly influence postoperative delirium together with other interacting variables.MethodsWe conducted a retrospective cohort study involving 527 participants with a preoperative diagnosis of suspected pheochromocytoma. CT characteristics, preoperative preparation, intraoperative infusion, estimated bleeding, use of intraoperative vasoactive drugs, and outcomes were obtained from all participants. Logistic regression and interaction effects were utilized to substantiate the research objectives.ResultsA total of 108 (20.5%) developed postoperative delirium, which was seen in 37 (18.0%) in the pheochromocytoma group and 71 (22.0%) in the non-pheochromocytoma group. The incidence of postoperative delirium showed no statistically significant differences in the two groups. A positive association between the duration of phenoxybenzamine use and the risk of postoperative delirium was observed (OR = 1.05, 95%CI = 1.03–1.08, p

The study focuses on the critically endangered Dabry’s sturgeon (Acipenser dabryanus), a species on the brink of extinction in the wild. This research investigates the role of the Forkhead box protein L2 (foxl2) in the gonadal development and differentiation of this species. The foxl2 gene, known for its role in various physiological processes, including sexual maturation, is hypothesized to play a significant role in the sex differentiation of Dabry’s sturgeon. This study cloned the full-length cds sequence of the foxl2 gene and analyzed its expression across various tissues, focusing on its response to estradiol treatment. Our findings indicate that foxl2 is predominantly expressed in ovaries and shows a dose-dependent response to estradiol, suggesting its potential role in ovarian differentiation. This research underscores the importance of foxl2 in understanding reproductive biology and offers a foundation for future conservation strategies.

BackgroundBiliary stricture caused by malignant tumors is known as Malignant Biliary Stricture (MBS). MBS is challenging to differentiate clinically, and accurate diagnosis is crucial for patient prognosis and treatment. This study aims to identify the risk factors for malignancy in all patients diagnosed with biliary stricture by Endoscopic Retrograde Cholangiopancreatography (ERCP), and to develop an effective clinical predictive model to enhance diagnostic outcomes.MethodologyThrough a retrospective study, data from 398 patients diagnosed with biliary stricture using ERCP between January 2019 and January 2023 at two institutions: the First People’s Hospital affiliated with Jiangsu University and the Second People’s Hospital affiliated with Soochow University. The study began with a preliminary screening of risk factors using univariate regression. Lasso regression was then applied for feature selection. The dataset was divided into a training set and a validation set in an 8:2 ratio. We analyzed the selected features using seven machine learning algorithms. The best model was selected based on the Area Under the Receiver Operating Characteristic (ROC) Curve (AUROC) and other evaluation indicators. We further evaluated the model’s accuracy using calibration curves and confusion matrices. Additionally, we used the SHAP method for interpretability and visualization of the model’s predictions.ResultsRF model is the best model, achieved an AUROC of 0.988. Shap result indicate that age, stricture location, stricture length, carbohydrate antigen 199 (CA199), total bilirubin (TBil), alkaline phosphatase (ALP), (Direct Bilirubin) DBil/TBil, and CA199/C-Reactive Protein (CRP) were risk factors for MBS, and the CRP is a protective factor.ConclusionThe model’s effectiveness and stability were confirmed, accurately identifying high-risk patients to guide clinical decisions and improve patient prognosis.

BackgroundCircadian rhythms impact metabolism and the therapeutic effects of drugs. The purpose of this study was to determine the association between PER and CRY polymorphisms and caffeine citrate treatment response in infants with apnea of prematurity.MethodsA total of 221 preterm infants of gestational age 0.05). Infants in the non-response groups had a higher incidence of moderate and severe bronchopulmonary dysplasia (BPD) (P = 0.043), retinopathy of prematurity (ROP) (P = 0.035), and invasive ventilation (P = 0.027), and their duration of oxygen use (P = 0.041) was longer. When corrected for false discovery rate, the PER3 rs228669 recessive model (PFDR = 0.045) and the over-dominant model (PFDR = 0.045) were both associated with caffeine citrate treatment response. Preterm infants with the rs228669 CC genotype had a significantly lower rate of caffeine citrate non-response in the recessive model (OR = 0.28, 95% CI = 0.12–0.66), which was significantly higher in preterm infants with the CT genotype in the over-dominant model (OR = 4.18, 95% CI = 1.64–10.66). GMDR analysis revealed an interaction between the PER and CRY genes (P

BackgroundHyperglycemia in pregnancy (HGP) has generally been considered a risk factor associated with adverse outcomes in offspring, but its impact on the short-term outcomes of very preterm infants remains unclear.MethodsA secondary analysis was performed based on clinical data collected prospectively from 28 hospitals in seven regions of China from September 2019 to December 2020. According to maternal HGP, all infants were divided into the HGP group or the non-HGP group. A propensity score matching analysis was used to adjust for confounding factors, including gestational age, twin or multiple births, sex, antenatal steroid administration, delivery mode and hypertensive disorders of pregnancy. The main complications and the short-term growth status during hospitalization were evaluated in the HGP and non-HGP groups.ResultsA total of 2,514 infants were eligible for analysis. After matching, there were 437 infants in the HGP group and 874 infants in the non-HGP group. There was no significant difference between the two groups in main complications including respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, retinopathy of prematurity, patent ductus arteriosus, culture positive sepsis, intraventricular hemorrhage, periventricular leukomalacia, anemia, feeding intolerance, metabolic bone disease of prematurity, or parenteral nutrition-associated cholestasis. The incidences of extrauterine growth retardation and increased growth retardation for weight and head circumference in the non-HGP group were all higher than those in the HGP group after matching (P

Background and objectiveStent-assisted coil (SAC) embolization is a commonly used endovascular treatment for unruptured intracranial aneurysms (UIAs) but can be associated with symptomatic delayed intracerebral hemorrhage (DICH). Our study aimed to investigate the hemodynamic risk factors contributing to DICH following SAC embolization and to establish a classification for DICH predicated on hemodynamic profiles.MethodsThis retrospective study included patients with UIAs located in the internal carotid artery (ICA) treated with SAC embolization at our institution from January 2021 to January 2022. We focused on eight patients who developed postoperative DICH and matched them with sixteen control patients without DICH. Using computational fluid dynamics, we evaluated the hemodynamic changes in distal arteries [terminal ICA, the anterior cerebral artery (ACA), and middle cerebral artery (MCA)] pre-and post-embolization. We distinguished DICH-related arteries from unrelated ones (ACA or MCA) and compared their hemodynamic alterations. An imbalance index, quantifying the differential in flow velocity changes between ACA and MCA post-embolization, was employed to gauge the flow distribution in distal arteries was used to assess distal arterial flow distribution.ResultsWe identified two types of DICH based on postoperative flow alterations. In type 1, there was a significant lower in the mean velocity increase rate of the DICH-related artery compared to the unrelated artery (−47.25 ± 3.88% vs. 42.85 ± 3.03%; p

The HAP clade, mainly including Helichrysum Mill, Anaphalis DC., and Pseudognaphalium Kirp., is a major component of tribe Gnaphalieae (Asteraceae). In this clade, Anaphalis represents the largest genus of Asian Gnaphalieae. The intergeneric relationships among Anaphalis and its related genera and the infrageneric taxonomy of this genus are complex and remain controversial. However, there are few studies that have focused on these issues. Herein, based on the current most comprehensive sampling of the HAP clade, especially Anaphalis, we conducted phylogenetic analyses using chloroplast (cp) genome and nuclear ribosomal DNA (nrDNA) to evaluate the relationships within HAP clade, test the monophyly of Anaphalis, and examine the infrageneric taxonomy of this genus. Meanwhile, the morphological characters were verified to determine the circumscription and infrageneric taxonomy system of Anaphalis. Additionally, the biogeographical history, diversification processes, and evolution of crucial morphological characters were estimated and inferred. Our phylogenetic analyses suggested that Anaphalis is polyphyletic because it nested with Helichrysum and Pseudognaphalium. Two and four main clades of Anaphalis were identified in cp genome and nrDNA trees, respectively. Compared with nrDNA trees, the cp genome trees were more effective for phylogenetic resolution. After comprehensively analyzing morphological and phylogenetic evidence, it was concluded that the achene surface ornamentation and leaf base showed less homoplasy and supported the two Anaphalis lineages that were inferred from cp genome. Our biogeographical analyses based on cp genome indicated that HAP clade underwent rapid diversification from late Miocene to Pliocene. The two Anaphalis lineages appeared to have originated in Africa, then spread to Western and Southern Asia, and subsequently moved into Southwestern China forming a diversity center. The dispersal patterns of the two Anaphalis lineages were different. One dispersed around the world, except in Africa and South America. The other one dispersed to Eastern and Southeastern Asia from the ancestral origin region.

Introduction: Despite the clinical value of Chinese herbal medicine (CHM), restricted comprehension of its toxicity limits the secure and efficacious application. Previous studies primarily focused on exploring specific toxicities within CHM, without providing an overview of CHM’s toxicity. The absence of a quantitative assessment of focal points renders the future research trajectory ambiguous. Therefore, this study aimed to reveal research trends and areas of concern for the past decade.Methods: A cross-sectional study was conducted on publications related to CHM and toxicity over the past decade from Web of Science Core Collection database. The characteristics of the publication included publication year, journal, institution, funding, keywords, and citation counts were recorded. Co-occurrence analysis and trend topic analysis based on bibliometric analysis were conducted on keywords and citations.Results: A total of 3,225 publications were analyzed. Number of annal publications increased over the years, with the highest number observed in 2022 (n = 475). The Journal of Ethnopharmacology published the most publications (n = 425). The most frequently used toxicity classifications in keywords were hepatotoxicity (n = 119) or drug-induced liver injury (n = 48), and nephrotoxicity (n = 40). Co-occurrence analysis revealed relatively loose connections between CHM and toxicity, and their derivatives. Keywords emerging from trend topic analysis for the past 3 years (2019–2022) included ferroptosis, NLRP3 inflammasome, machine learning, network pharmacology, traditional uses, and pharmacology.Conclusion: Concerns about the toxicity of CHM have increased in the past decade. However, there remains insufficient studies that directly explore the intersection of CHM and toxicity. Hepatotoxicity and nephrotoxicity, as the most concerned toxicity classifications associated with CHM, warrant more in-depth investigations. Apoptosis was the most concerned toxicological mechanism. As a recent increase in attention, exploring the mechanisms of ferroptosis in nephrotoxicity and NLRP3 inflammasome in hepatotoxicity could provide valuable insights. Machine learning and network pharmacology are potential methods for future studies.

BackgroundThe objective of this study was to explore the association between the sarcopenia index and abnormal liver function in adult individuals in the United States.MethodologyThis study employed a rigorous cross-sectional analysis of data derived from the National Health and Nutrition Examination Survey (NHANES) conducted between 2017 and 2018. The primary objective was to investigate the correlation between the sarcopenia index and abnormal liver function. To achieve this, an advanced multivariate regression model was utilized, allowing for comprehensive analysis and meticulous adjustment of relevant variables. To ensure the robustness of the findings, a visually appealing smooth curve was constructed, and a two-stage regression model was applied for validation. Additionally, a detailed gender-stratified analysis was conducted to further explore the association between the sarcopenia index and abnormal liver function within distinct subgroups.ResultsThrough our rigorous participant selection process, a total of 1756 individuals were included in the study. The meticulously adjusted multivariate regression model revealed a significant negative association between the sarcopenia index and abnormal liver function, with an adjusted odds ratio (OR) of 0.73 and a 95% confidence interval (CI) ranging from 0.63 to 0.86. The robustness of this association was further supported by the visually appealing smooth curve plot. Moreover, in the gender-stratified subgroup analysis, after meticulous adjustment for confounding factors, notable differences in this association emerged (males: OR = 0.8, 95% CI: 0.66–0.98; females: OR = 0.61, 95% CI: 0.47–0.79).ConclusionThis cross-sectional study yields robust evidence indicating a negative correlation between the sarcopenia index and abnormal liver function, predominantly observed among females.

The objective of this experiment was to determine the effect of low crude protein (CP) diets containing increasing amounts of enzymolytic soybean meal (ESBM) on growth performance, economic benefit and organ development and the role of cecal fermentation and microbiota in broilers. A total of 360 one-day-old Arbor Acres chicks were randomly allocated into 6 groups with 6 replicates and 10 chicks each. The six dietary treatments consisted of a standard high-CP diet (PC), a low-CP diet (NC), and an NC diet with 0.5, 1.0, 1.5%, or 2.0% ESBM. The experiment lasted for 42 days. Compared to PC, NC showed decreased (p 0.05), while the cecal abundances of Bacteroides, Faecalibacterium and Clostridium IV increased (p

Due to the complicated transport and reactive behavior of organic contamination in groundwater, the development of mathematical models to aid field remediation planning and implementation attracts increasing attentions. In this study, the approach coupling response surface methodology (RSM), artificial neural networks (ANN), and kinetic models was implemented to model the degradation effects of nano-zero-valent iron (nZVI) activated persulfate (PS) systems on benzene, a common organic pollutant in groundwater. The proposed model was applied to optimize the process parameters in order to help predict the effects of multiple factors on benzene degradation rate. Meanwhile, the chemical oxidation kinetics was developed based on batch experiments under the optimized reaction conditions to predict the temporal degradation of benzene. The results indicated that benzene (0.25 mmol) would be theoretically completely oxidized in 1.45 mM PS with the PS/nZVI molar ratio of 4:1 at pH 3.9°C and 21.9 C. The RSM model predicted well the effects of the four factors on benzene degradation rate (R2 = 0.948), and the ANN with a hidden layer structure of [8-8] performed better compared to the RSM (R2 = 0.980). In addition, the involved benzene degradation systems fit well with the Type-2 and Type-3 pseudo-second order (PSO) kinetic models with R2 > 0.999. It suggested that the proposed statistical and kinetic-based modeling approach is promising support for predicting the chemical oxidation performance of organic contaminants in groundwater under the influence of multiple factors.

Curcumae Longae Rhizoma (turmeric), Curcumae Radix and Curcumae Rhizoma are derived from the Curcuma species, and have gradually become three of the most commonly used medicinal herbs in China due to their different origins, processing methods and medicinal part. These three herbs have certain similarities in morphology, chemical composition, and pharmacological effects. All three of these herbs contain curcuminoids and volatile oil compounds, which exhibit anti-inflammatory, anti-tumor, antioxidant, and neuroprotective properties, although modern clinical applications have their own requirements. At present, there is no systematic guidelines for the clinical application of these three of Curcuma species; consequently, there is a high risk of unwanted phenomena associated with the mixing and indiscriminate use of these herbs. In this review, we focus predominantly on morphology, chemical composition, and the pharmacological activity of these three Curcuma herbs and summarize the current status of research in this field. Our goal is to provide a better understanding of clinical value of these Curcuma species so that we can provide reference guidelines for their further development, utilization and rational clinical application.

The infrageneric taxonomy system, species delimitation, and interspecies systematic relationships of Leontopodium remain controversial and complex. However, only a few studies have focused on the molecular phylogeny of this genus. In this study, the characteristics of 43 chloroplast genomes of Leontopodium and its closely related genera were analyzed. Phylogenetic relationships were inferred based on chloroplast genomes and nuclear ribosomal DNA (nrDNA). Finally, together with the morphological characteristics, the relationships within Leontopodium were identified and discussed. The results showed that the chloroplast genomes of Filago, Gamochaeta, and Leontopodium were well-conserved in terms of gene number, gene order, and GC content. The most remarkable differences among the three genera were the length of the complete chloroplast genome, large single-copy region, small single-copy region, and inverted repeat region. In addition, the chloroplast genome structure of Leontopodium exhibited high consistency and was obviously different from that of Filago and Gamochaeta in some regions, such as matk, trnK (UUU)-rps16, petN-psbM, and trnE (UUC)-rpoB. All the phylogenetic trees indicated that Leontopodium was monophyletic. Except for the subgeneric level, our molecular phylogenetic results were inconsistent with the previous taxonomic system, which was based on morphological characteristics. Nevertheless, we found that the characteristics of the leaf base, stem types, and carpopodium base were phylogenetically correlated and may have potential value in the taxonomic study of Leontopodium. In the phylogenetic trees inferred using complete chloroplast genomes, the subgen. Leontopodium was divided into two clades (Clades 1 and 2), with most species in Clade 1 having herbaceous stems, amplexicaul, or sheathed leaves, and constricted carpopodium; most species in Clade 2 had woody stems, not amplexicaul and sheathed leaves, and not constricted carpopodium.

ObjectivesThe Kaiser scoring system for breast magnetic resonance imaging is a clinical decision-making tool for diagnosing breast lesions. However, the Kaiser score (KS) did not include the evaluation of breast vascularity. Therefore, this study aimed to use KS combined with breast vascular assessment, defined as KS*, and investigate the effectiveness of KS* in differentiating benign from malignant breast lesions.MethodsThis retrospective study included 223 patients with suspicious breast lesions and pathologically verified results. The histopathological diagnostic criteria were according to the fifth edition of the WHO classification of breast tumors. The KS* was obtained after a joint evaluation combining the original KS and breast vasculature assessment. The receiver operating characteristic (ROC) curve was used for comparing differences in the diagnostic performance between KS* and KS, and the area under the receiver operating characteristic (AUC) was compared.ResultsThere were 119 (53.4%) benign and 104 (46.6%) malignant lesions in total. The overall sensitivity, specificity, and accuracy of increased ipsilateral breast vascularity were 69.2%, 76.5%, and 73.1%, respectively. The overall sensitivity, specificity, and accuracy of AVS were 82.7%, 76.5%, and 79.4%, respectively. For all lesions included the AUC of KS* was greater than that of KS (0.877 vs. 0.858, P = 0.016). The largest difference in AUC was observed in the non-mass subgroup (0.793 vs. 0.725, P = 0.029).ConclusionIpsilaterally increased breast vascularity and a positive AVS sign were significantly associated with malignancy. KS combined with breast vascular assessment can effectively improve the diagnostic ability of KS for breast lesions, especially for non-mass lesions.

BackgroundThe shaping of an accurate and stable microcatheter plays a vital role in the successful embolization of intracranial aneurysms. Our study aimed to investigate the application and the role of AneuShape™ software in microcatheter shaping for intracranial aneurysm embolization.MethodsFrom January 2021 to June 2022, 105 patients with single unruptured intracranial aneurysms were retrospectively analyzed with or without AneuShape™ software to assist in microcatheter shaping. The rates of microcatheter accessibility, accurate positioning, and stability for shaping were analyzed. During the operation, fluoroscopy duration, radiation dose, immediate postoperative angiography, and procedure-related complications were evaluated.ResultsCompared to the manual group, aneurysm-coiling procedures involving the AneuShape™ software exhibited superior results. The use of the software resulted in a lower rate of reshaping microcatheters (21.82 vs. 44.00%, p = 0.015) and higher rates of accessibility (81.82 vs. 58.00%, p = 0.008), better positioning (85.45 vs. 64.00%, p = 0.011), and higher stability (83.64 vs. 62.00%, p = 0.012). The software group also required more coils for both small (

BackgroundTime-restricted feeding (TRF) has become a popular weight loss method in recent years. It is widely used in the nutritional treatment of normal obese people and obese people with chronic diseases such as diabetes mellitus and hypertension, and has shown many benefits. However, most TRF studies have excluded chronic kidney disease (CKD) patients, resulting in a lack of sufficient evidence-based practice for the efficacy and safety of TRF therapy for CKD. Therefore, we explore the efficacy and safety of TRF in overweight and obese patients with moderate-to-severe stage CKD through this pilot study, and observe patient compliance to assess the feasibility of the therapy.MethodsThis is a prospective, non-randomized controlled short-term clinical trial. We recruited overweight and obese patients with CKD stages 3-4 from an outpatient clinic and assigned them to either a TRF group or a control diet (CD) group according to their preferences. Changes in renal function, other biochemical data, anthropometric parameters, gut microbiota, and adverse events were measured before the intervention and after 12 weeks.ResultsThe change in estimated glomerular filtration rate (eGFR) before and after intervention in the TRF group (Δ = 3.1 ± 5.3 ml/min/1.73m2) showed significant improvement compared with the CD group (Δ = -0.8 ± 4.4 ml/min/1.73m2). Furthermore, the TRF group had a significant decrease in uric acid (Δ = -70.8 ± 124.2 μmol/L), but an increase in total protein (Δ = 1.7 ± 2.5 g/L), while the changes were inconsistent for inflammatory factors. In addition, the TRF group showed a significant decrease in body weight (Δ = -2.8 ± 2.9 kg) compared to the CD group, and body composition indicated the same decrease in body fat mass, fat free mass and body water. Additionally, TRF shifted the gut microbiota in a positive direction.ConclusionPreliminary studies suggest that overweight and obese patients with moderate-to-severe CKD with weight loss needs, and who were under strict medical supervision by healthcare professionals, performed TRF with good compliance. They did so without apparent adverse events, and showed efficacy in protecting renal function. These results may be due to changes in body composition and alterations in gut microbiota.

The outcomes of patients with diffuse large B-cell lymphoma (DLBCL) vary widely, and about 40% of them could not be cured by the standard first-line treatment, R-CHOP, which could be due to the high heterogeneity of DLBCL. Here, we aim to construct a prognostic model based on the genetic signature of metabolic heterogeneity of DLBCL to explore therapeutic strategies for DLBCL patients. Clinical and transcriptomic data of one training and four validation cohorts of DLBCL were obtained from the GEO database. Metabolic subtypes were identified by PAM clustering of 1,916 metabolic genes in the 7 major metabolic pathways in the training cohort. DEGs among the metabolic clusters were then analyzed. In total, 108 prognosis-related DEGs were identified. Through univariable Cox and LASSO regression analyses, 15 DEGs were used to construct a risk score model. The overall survival (OS) and progression-free survival (PFS) of patients with high risk were significantly worse than those with low risk (OS: HR 2.86, 95%CI 2.04–4.01, p < 0.001; PFS: HR 2.42, 95% CI 1.77–3.31, p < 0.001). This model was also associated with OS in the four independent validation datasets (GSE10846: HR 1.65, p = 0.002; GSE53786: HR 2.05, p = 0.02; GSE87371: HR 1.85, p = 0.027; GSE23051: HR 6.16, p = 0.007) and PFS in the two validation datasets (GSE87371: HR 1.67, p = 0.033; GSE23051: HR 2.74, p = 0.049). Multivariable Cox analysis showed that in all datasets, the risk model could predict OS independent of clinical prognosis factors (p < 0.05). Compared with the high-risk group, patients in the low-risk group predictively respond to R-CHOP (p = 0.0042), PI3K inhibitor (p < 0.05), and proteasome inhibitor (p < 0.05). Therefore, in this study, we developed a signature model of 15 DEGs among 3 metabolic subtypes, which could predict survival and drug sensitivity in DLBCL patients.

ObjectivesThe aim of this study was to evaluate the shape of the dose-response relationship between body mass index (BMI) and atrial fibrillation (AF) recurrence in patients who have undergone radiofrequency ablation.MethodsStudies investigating BMI and AF recurrence in patients with AF after ablation were identified through electronic searches in the PubMed, EMBASE, and Cochrane Library databases. The potential non-linear relationship was fitted using robust error meta-regression. Our study was registered with PROSPERO (CRD42019121373).ResultsTwenty-six cohort studies with 7,878 cases/26,450 individuals were included, and a linear dose-response relationship between BMI and AF recurrence (Pnon–linearity = 0.12) was found. The risk of AF recurrence in patients with a BMI over 28 was significantly increased. Specifically, for each 5 kg/m2 increase in BMI, the risk of AF recurrence increased by 15% (95% CI: 1.08–1.22) with moderate heterogeneity (I2 = 53%). Subgroup analyses showed that the pooled risk ratio was not significantly changed in subgroup analysis adjustment for the following important potential intermediate factors: left atrial diameter and obstructive sleep apnea.ConclusionThis study showed that there is a borderline positive linear association between BMI and AF recurrence post ablation. Overweight and obesity are significantly associated with AF recurrence.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42019128770.

Photoplethysmography (PPG) signal is potentially suitable in atrial fibrillation (AF) detection for its convenience in use and similarity in physiological origin to electrocardiogram (ECG). There are a few preceding studies that have shown the possibility of using the peak-to-peak interval of the PPG signal (PPIp) in AF detection. However, as a generalized model, the accuracy of an AF detector should be pursued on the one hand; on the other hand, its generalizability should be paid attention to in view of the individual differences in PPG manifestation of even the same arrhythmia and the existence of sub-types. Moreover, a binary classifier for atrial fibrillation and normal sinus rhythm is not convincing enough for the similarity between AF and ectopic beats. In this study, we project the atrial fibrillation detection as a multiple-class classification and try to propose a training pipeline that is advantageous both to the accuracy and generalizability of the classifier by designing and determining the configurable options of the pipeline, in terms of input format, deep learning model (with hyperparameter optimization), and scheme of transfer learning. With a rigorous comparison of the possible combinations of the configurable components in the pipeline, we confirmed that first-order difference of heartbeat sequence as the input format, a 2-layer CNN–1-layer Transformer hybridR model as the learning model and the whole model fine-tuning as the implementing scheme of transfer learning is the best combination for the pipeline (F1 value: 0.80, overall accuracy: 0.87)R.

ObjectiveTo investigate the protective effect of high-proportion breast milk feeding (>50%) on intraventricular hemorrhage (IVH) in very preterm infants (VPIs).MethodsThis was a retrospective secondary analysis of a prospective multi-center study, which included 604 VPIs from six hospitals in eastern China between September 2019 and December 2020. The 604 VPIs were divided into two groups according to whether IVH occurred. High-proportion breast milk feeding was defined as breast milk accounting for 51–100% of the total feeding amount both within 7 days and throughout the hospitalization. The IVH grades and the rate of high-proportion breast milk feeding were analyzed. Furthermore, to explore the relationship between high-proportion breast milk feeding and IVH grading, the VPIs' general information, perinatal factors, growth, and nutritional status during hospitalization, and related complications were compared between the two groups.ResultsHigh-proportion breast milk feeding was reported in 63.41% of the VPIs. Furthermore, IVH grades I–II and III–IV were noted in 39.73% (240/604) and 1.66% (10/604) of the VPIs, respectively. Univariate analysis revealed that IVH occurrence in VPIs is influenced by perinatal factors, invasive respiratory therapy, high-proportion breast milk feeding, start feeding with breast milk, the cumulative amount of early parenteral nutrition, postnatal complications, physical growth, and other factors (P < 0.05). After adjustments for gestational age, birth weight, and possible influencing factors through binary logistic regression analysis, the results revealed that high-proportion breast milk feeding and and start feeding with breast milk were associated with a lower total incidence of IVH. Further stratification showed that high-proportion breast milk feeding was associated with a lower incidence of grade I–II IVH. Similarly, after adjusting for the same factors, breast milk feeding >50% in the 1st week was associated with a decreased incidence of total IVH and further stratification showed that it was associated with a lower incidence of grade I–II IVH.ConclusionHigh-proportion breast milk feeding and breast milk feeding more than 50% of total intake during the 1st week might be protective factors for IVH grade I–II in VPIs, which further verified the neuroprotective effect of breast milk. In clinical practice, the construction of breast milk banks should be strengthened, breast milk feeding should be encouraged in neonatal intensive care units, and efforts should be made to increase breast milk feeding rates to improve the outcomes of VPIs.

ObjectiveThe aim of the present study was to examine the value of high-density lipoprotein (HDL) subfractions for predicting cardiovascular events (CVEs) in untreated type 2 diabetes mellitus (T2DM) patients with stable coronary artery disease (SCAD) using an age- and gender-matched case-control study.MethodsIn total, 185 SCAD patients and 185 T2DM patients with SCAD were enrolled and subjected to a clinical follow-up of CVEs. HDL subfractions were analyzed using the Quantimetrix Lipoprint System. The relationship between HDL subfractions and CVEs in T2DM patients with SCAD was evaluated by Kaplan–Meier analysis and Cox proportional hazard models.ResultsDuring a median 37.7-month follow-up, T2DM patients with SCAD had a higher percentage of CVEs compared to SCAD patients (p=0.039). The concentration of the combined intermediate and small HDL-C subfraction (defined as the mixed HDL subfraction) was related to the event incidence in T2DM patients with SCAD (p=0.004), and it was positively associated with increased CVEs even after adjustment in three models. Kaplan-Meier curve analysis indicated that T2DM patients with SCAD in the high mixed HDL subfraction group (>28 mg/dL) had lower event-free survival rates (p=0.008).ConclusionsElevated concentration of the mixed HDL subfraction predicts events in T2DM patients with SCAD.

BackgroundAn increasing number of innovations have been discovered for treating hepatocellular carcinoma (HCC or commonly called HCC) therapy, Ferroptosis and mitochondrial metabolism are essential mechanisms of cell death. These pathways may act as functional molecular biomarkers that could have important clinical significance for determining individual differences and the prognosis of HCC. The aim of this study was to construct a stable and reliable comprehensive model of genetic features and clinical factors associated with HCC prognosis.MethodsIn this study, we used RNA-sequencing (fragments per kilobase of exon model per million reads mapped value) data from the Cancer Genome Atlas (TCGA) database to establish a prognostic model. We enrolled 104 patients for further validation. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analyses (KEGG) analysis were used for the functional study of differentially expressed genes. Pan-cancer analysis was performed to evaluate the function of the Differentially Expressed Genes (DEGs). Thirteen genes were identified by univariate and least absolute contraction and selection operation (LASSO) Cox regression analysis. The prognostic model was visualized using a nomogram.ResultsWe found that eight genes, namely EZH2, GRPEL2, PIGU, PPM1G, SF3B4, TUBG1, TXNRD1 and NDRG1, were hub genes for HCC and differentially expressed in most types of cancer. EZH2, GRPEL2 and NDRG1 may indicate a poor prognosis of HCC as verified by tissue samples. Furthermore, a gene set variation analysis algorithm was created to analyze the relationship between these eight genes and oxidative phosphorylation, mitophagy, and FeS-containing proteins, and it showed that ferroptosis might affect inflammatory-related pathways in HCC.ConclusionEZH2, GRPEL2, NDRG1, and the clinical factor of tumor size, were included in a nomogram for visualizing a prognostic model of HCC. This nomogram based on a functional study and verification by clinical samples, shows a reliable performance of patients with HCC.

Education for sustainable development (ESD) is an important guideline for United Nations Sustainable Development Goals. Students' creative thinking can be applied to various disciplines, promoting sustainable learning. Most of Taiwan's beauty and hairdressing technical education teachers mainly teach students to imitate, and students' works lack creativity and thinking. A total of 43 higher vocational college students participated, 23 of whom were in the experimental group using the creative thinking teaching method and 20 of whom were in the control group using the traditional teaching method. The results show that the creative thinking teaching method can effectively improve students' learning outcomes in the multimedia material creation course, including breaking through the limitation of thinking, putting forward different ideas and answers, and constantly innovating, to make the presented results more creative and meaningful. The creative thinking teaching methods solve students' trouble in creative problem solving, enhance students' problem solving and critical thinking skills, and improve students' involvement in the study.

Liposome is a conventional drug delivery system which has been widely used in the pharmacy field. However, its applications are greatly restricted in clinical practice by the disadvantages of cholesterol and nonselective distribution. Herein, a novel platform for anti-tumor drug delivery was developed by incorporating an amphiphilic stachydrine-octadecane conjugate (SS) as the mitochondria-targeting molecule onto the triptolide-liposome surfaces (SS-TP LPs). The polyethylene glycol (PEG) and the suitable particle size (about 133 nm) of liposomes facilitated their stabilities, the long half-life in blood and the escape from the rapid elimination. The SS-TP LPs were internalized and accumulated into the mitochondria of cancer cells in a time-dependent manner, followed by triggering permeabilization of the mitochondrial outer membrane by inhibiting Bcl-2, and then further caused greater cancer cell death via releasing cytochrome C and initiating a cascade of caspase 3 reactions. In the Pan02 tumor-bearing mice, the SS-TP LPs showed significant efficacy in inhibiting tumor growth and reducing tumor size but synchronously exhibited specific mitochondria-targeting and much lower subacute toxicity compared with the free TP and TP LPs. Our study suggests that SS-TP LPs can be a promising anticancer drug delivery system for mitochondria-targeted therapy in pancreatic cancer.

Background: RNA modification is one of the epigenetic mechanisms that regulates post-transcriptional gene expression, and abnormal RNA modifications have been reported to play important roles in tumorigenesis. N7-methylguanosine (m7G) is an essential modification at the 5′ cap of human mRNA. However, a systematic and pan-cancer analysis of the clinical relevance of m7G related regulatory genes is still lacking.Methods: We used univariate Cox model and Kaplan-Meier analysis to generate the forest plot of OS, PFI, DSS and identified the correlation between the altered expression of m7G regulators and patient survival in 33 cancer types from the TCGA and GTEx databases. Then, the “estimate” R-package, ssGSEA and CIBERSORT were used to depict the pan-cancer immune landscape. Through Spearman’s correlation test, we analyzed the correlation between m7G regulators and the tumor microenvironment (TME), immune subtype, and drug sensitivity of the tumors, which was further validated in NSCLC. We also assessed the changes in the expression of m7G related regulatory genes in NSCLC with regards to the genetic and transcriptional aspects and evaluated the correlation of METTL1 and WDR4 expression with TMB, MSI and immunotherapy in pan-cancer.Results: High expression of most of the m7G regulators was significantly associated with worse prognosis. Correlation analyses revealed that the expression of majority of the m7G regulators was correlated with tumor immune infiltration and tumor stem cell scores. Drug sensitivity analysis showed that the expression of CYFP1,2 was closely related to drug sensitivity for various anticancer agents (p < 0.001). Analysis of the pan-cancer immune subtype revealed significant differences in the expression of m7G regulators between different immune subtypes (p < 0.001). Additionally, the types and proportions of mutations in METTL1 and WDR4 and their relevance to immunotherapy were further described.Conclusion: Our study is the first to evaluate the correlation between the altered expression of m7G regulators and patient survival, the degree of immune infiltration, TME and drug sensitivity in pan-cancer datasets.

ObjectiveTo investigate the incidence and related factors of extrauterine growth retardation (EUGR) and “true EUGR” in very preterm infants (VPI) from different regions of China.Materials and methodsClinical data of VPI were prospectively collected from 28 hospitals in seven different regions of China from September 2019 to December 2020. The infants were divided into a small for gestational age (SGA) group or non-SGA group at birth, with non-SGA infants at 36 weeks of gestation or at discharge being further divided into a EUGR group or a non-EUGR group. Infants in the EUGR and non-SGA group were defined as “true EUGR.” The general information of VPI, such as maternal complications during pregnancy, use of enteral nutrition and parenteral nutrition, and complications during hospitalization were compared between the groups.ResultsAmong the 2,514 VPI included in this study, 47.3, 41.5, and 33.3% of VPI were below the 10th percentile, and 22.6, 22.4, and 16.0% of VPI were below the 3rd percentile for weight, height, and head circumference at 36 weeks of gestation or at discharge, respectively, by the percentile on the 2013 Fenton curve. The incidences of EUGR and “true EUGR” evaluated by weight were 47.3 and 44.5%, respectively. Univariate analysis showed that there were statistically significant differences in the aspects of perinatal and nutritional characteristics, treatment, and complications between the groups. Multivariate analysis showed that in non-SGA infants, the cumulative caloric intake during the first week was a protective factor for “true EUGR,” while days to reach total enteral nutrition, late initiation of human milk fortifier, and moderate to severe bronchopulmonary dysplasia were independent risk factors for “true EUGR.”ConclusionMore attention should be paid to the nutritional management of VPI to prevent “true EUGR.” Cumulative caloric intake should be ensured and increased during the first week, total enteral nutrition should be achieved as early as possible, human milk fortifier should be added early, and moderate to severe bronchopulmonary dysplasia should be prevented. These strategies are very important for reducing the incidence of “true EUGR” in VPI.

The lantern exhibition at the Lantern Festival is an important traditional festival in Taiwan. Visitors play an important role in the promotion and sustainable development of intangible cultural heritage (ICH). In recent years, the involvement of digital technology in traditional lantern design and shows has contributed to the protection, inheritance, and promotion of ICH, there remains less research on using augmented reality (AR) with ICH tourism. In this study, AR is used for ICH lantern exhibition to discuss the learning experience in lantern tourism and the relationship between technology acceptance and satisfaction from the perspective of visitors, as well as evaluate what AR has on improving visitors’ awareness and learning experience. Then, primary variables of the technology acceptance model (TAM) are combined with generic learning outcomes (GLOs) to integrate ICH, education, and technology to expand TAM, building a new model to study the ICH learning experience. A questionnaire and observation are used. Respondents are visitors participating in the AR lantern exhibition in Taiwan, which is designed by the author. There is a total of 200 questionnaires collected in the end. The result shows that knowledge and understanding (KU), attitudes and values (AV), activity, behavior, and progression (ABP), and enjoyment, inspiration, and creativity (EIC) from GLOs have a positive effect on technology acceptance and actual use (AU). Therefore, visitors are satisfied with innovative and interesting technology learning experiences, enhancing learning interest and results. Besides, the interaction of the AR system improves visitors’ learning motivation, which shows the combination of AR technology with ICH tourism helps improve cultural awareness.

Phenotypic variation of morphological and physiological traits is assumed to be generated from spatial heterogeneity in environments, and it has been regarded as an important concern domain in evolutionary biology. Organs display markedly size variation among populations along environmental gradients and this variation is associated with changes in oxygen supply and energy demands. Here, we investigated geographical variation in the relative size of organs (i.e., brain, heart, lung, gallbladder, livers, spleen, kidneys, and digestive tract) among 14 populations of Andrew’s toad (Bufo andrewsi) transcending an elevational range from 864 to 2,367 m, and spanning 8° latitude. We found that although the relative sizes of the eight specific organs varied significantly among populations, none organ size was affected by altitude and latitude. However, based on the combined the new data and published data we found a negative relationship between the relative size of the heart and latitude, contrasting to the Hesse’s rule. We also found that the relative size of livers was positively linked to latitude, suggesting that more energy demands and intakes due to slower metabolism in high latitude shaped the evolution of larger livers.

The long-distance transport of iron (Fe) in the xylem is critical for maintaining systemic Fe homeostasis in plants. The loading form of Fe(II) into the xylem and the long-distance translocation form of Fe(III)–citrate have been identified, but how Fe(II) is oxidized to Fe(III) in the xylem remains unknown. Here, we showed that the cell wall-resided ferroxidases LPR1 and LPR2 (LPRs) were both specifically expressed in the vascular tissues of Arabidopsis thaliana, while disruption of both of them increased Fe(II) in the xylem sap and caused excessive Fe deposition in the xylem vessel wall under Fe-sufficient conditions. As a result, a large amount of Fe accumulated in both roots and shoots, hindering plant growth. Moreover, under low-Fe conditions, LPRs were preferentially induced in old leaves, but the loss of LPRs increased Fe deposition in the vasculature of older leaves and impeded Fe allocation to younger leaves. Therefore, disruption of both LPRs resulted in severer chlorosis in young leaves under Fe-deficient conditions. Taken together, the oxidation of Fe(II) to Fe(III) by LPRs in the cell wall of vasculature plays an important role in xylem Fe allocation, ensuring healthy Fe homeostasis for normal plant growth.

Cancer becomes one of the main causes of human deaths in the world due to the high incidence and mortality rate and produces serious economic burdens. With more and more attention is paid on cancer, its therapies are getting more of a concern. Previous research has shown that the occurrence, progression, and treatment prognosis of malignant tumors are closely related to genetic and gene mutation. CRISPR/Cas9 has emerged as a powerful method for making changes to the genome, which has extensively been applied in various cell lines. Establishing the cell and animal models by CRISPR/Cas9 laid the foundation for the clinical trials which possibly treated the tumor. CRISPR-Cas9-mediated genome editing technology brings a great promise for inhibiting migration, invasion, and even treatment of tumor. However, the potential off-target effect limits its clinical application, and the effective ethical review is necessary. The article reviews the molecular mechanisms of CRISPR/Cas9 and discusses the research and the limitation related to cancer clinical trials.

Airway epithelium plays critical roles in regulating airway surface liquid (ASL), the alteration of which causes mucus stasis symptoms. Allicin is a compound released from garlic and harbors the capacity of lung-protection. However, the potential regulatory effects of allicin on airway epithelium remain elusive. This study aimed to investigate the effects of allicin on ion transport across airway epithelium and evaluate its potential as an expectorant. Application of allicin induced Cl− secretion across airway epithelium in a concentration-dependent manner. Blockade of cystic fibrosis transmembrane conductance regulator (CFTR) or inhibition of adenylate cyclase-cAMP signaling pathway attenuated allicin-induced Cl− secretion in airway epithelial cells. The in vivo study showed that inhaled allicin significantly increased the ASL secretion in mice. These results suggest that allicin induces Cl− and fluid secretion across airway epithelium via activation of CFTR, which might provide therapeutic strategies for the treatment of chronic pulmonary diseases associated with ASL dehydration.

Dopa-responsive dystonia (DRD) is a group of movement disorders with genetic and clinical heterogeneity. Dramatic response to levodopa is the hallmark of DRD. Therefore, DRD cases with poor response to levodopa are rarely reported. In addition, the clinical outcomes from deep brain stimulation (DBS) in levodopa-resistant patients remain unclear. Here, we described the clinical outcome of pallidal stimulation in a DRD patient having a poor response to levodopa. The patient was a 25-year-old man and had a 7-year history of cervical dystonia. A novel frameshift mutation in the GCH1 gene was found in the patient as well as his elder sister and mother. Unfortunately, he had no response to a large dosage of levodopa/benserazide (600/150 mg per day) and onabotulinumtoxin A injection. Therefore, bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) was performed. With parameter adjustments, the severity of his torticollis was gradually improved and relieved substantially in the 8-month follow-up visit. Our current report highlights that GPi-DBS therapy leads to promising clinical outcomes for levodopa-resistant DRD.

Endometrial carcinoma (EC) is a common cause of cancer death in women, and having an early accurate prediction model to identify this disease is crucial. The aim of this study was to develop a new machine learning (ML) model-based diagnostic prediction model for EC. We collected data from consecutive patients between November 2012 and January 2021 at tertiary hospitals in central China. Inclusion criteria included women undergoing endometrial biopsy, dilation and curettage, or hysterectomy. A total of 9 features, including patient demographics, vital signs, and laboratory and ultrasound results, were selected in the final analysis. This new model was combined with three top optimal ML methods, namely, logistic regression, gradient-boosted decision tree, and random forest. A total of 1,922 patients were eligible for final analysis and modeling. The ensemble model, called TJHPEC, was validated in an internal validation cohort and two external validation cohorts. The results showed that the AUC values were 0.9346, 0.8341, and 0.8649 for the prediction of total EC and 0.9347, 0.8073, and 0.871 for prediction of stage I EC. Nine clinical features were confirmed to be highly related to the prediction of EC in TJHPEC. In conclusion, our new model may be accurate for identifying EC, especially in the early stage, in the general population of central China.

Touch as a modality in social communication has been getting more attention with recent developments in wearable technology and an increase in awareness of how limited physical contact can lead to touch starvation and feelings of depression. Although several mediated touch methods have been developed for conveying emotional support, the transfer of emotion through mediated touch has not been widely studied. This work addresses this need by exploring emotional communication through a novel wearable haptic system. The system records physical touch patterns through an array of force sensors, processes the recordings using novel gesture-based algorithms to create actuator control signals, and generates mediated social touch through an array of voice coil actuators. We conducted a human subject study (N = 20) to understand the perception and emotional components of this mediated social touch for common social touch gestures, including poking, patting, massaging, squeezing, and stroking. Our results show that the speed of the virtual gesture significantly alters the participants' ratings of valence, arousal, realism, and comfort of these gestures with increased speed producing negative emotions and decreased realism. The findings from the study will allow us to better recognize generic patterns from human mediated touch perception and determine how mediated social touch can be used to convey emotion. Our system design, signal processing methods, and results can provide guidance in future mediated social touch design.

Purpose: Endometrial thickness is one of the most important indicators in endometrial disease screening and diagnosis. Herein, we propose a method for automated measurement of endometrial thickness from transvaginal ultrasound images.Methods: Accurate automated measurement of endometrial thickness relies on endometrium segmentation from transvaginal ultrasound images that usually have ambiguous boundaries and heterogeneous textures. Therefore, a two-step method was developed for automated measurement of endometrial thickness. First, a semantic segmentation method was developed based on deep learning, to segment the endometrium from 2D transvaginal ultrasound images. Second, we estimated endometrial thickness from the segmented results, using a largest inscribed circle searching method. Overall, 8,119 images (size: 852 × 1136 pixels) from 467 cases were used to train and validate the proposed method.Results: We achieved an average Dice coefficient of 0.82 for endometrium segmentation using a validation dataset of 1,059 images from 71 cases. With validation using 3,210 images from 214 cases, 89.3% of endometrial thickness errors were within the clinically accepted range of ±2 mm.Conclusion: Endometrial thickness can be automatically and accurately estimated from transvaginal ultrasound images for clinical screening and diagnosis.

Coleanthus subtilis (Tratt.) Seidel (Poaceae) is an ephemeral grass from the monotypic genus Coleanthus Seidl, which grows on wet muddy areas such as fishponds or reservoirs. As a rare species with strict habitat requirements, it is protected at international and national levels. In this study, we sequenced its whole chloroplast genome for the first time using the next-generation sequencing (NGS) technology on the Illumina platform, and performed a comparative and phylogenetic analysis with the related species in Poaceae. The complete chloroplast genome of C. subtilis is 135,915 bp in length, with a quadripartite structure having two 21,529 bp inverted repeat regions (IRs) dividing the entire circular genome into a large single copy region (LSC) of 80,100 bp and a small single copy region (SSC) of 12,757 bp. The overall GC content is 38.3%, while the GC contents in LSC, SSC, and IR regions are 36.3%, 32.4%, and 43.9%, respectively. A total of 129 genes were annotated in the chloroplast genome, including 83 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. The accD gene and the introns of both clpP and rpoC1 genes were missing. In addition, the ycf1, ycf2, ycf15, and ycf68 were pseudogenes. Although the chloroplast genome structure of C. subtilis was found to be conserved and stable in general, 26 SSRs and 13 highly variable loci were detected, these regions have the potential to be developed as important molecular markers for the subfamily Pooideae. Phylogenetic analysis with species in Poaceae indicated that Coleanthus and Phippsia were sister groups, and provided new insights into the relationship between Coleanthus, Zingeria, and Colpodium. This study presents the initial chloroplast genome report of C. subtilis, which provides an essential data reference for further research on its origin.

Objective: To describe the clinical presentation and novel mutation in the coxsackie and adenovirus receptor-like membrane protein (CLMP) gene in a Chinese family with congenital short bowel syndrome (CSBS).Methods: We collected clinical data from a Chinese family with inherited CSBS, and performed whole exon sequencing of the children and their parents. The pathogenic sites of candidate genes were targeted, and the detected exon deletions were verified by quantitative PCR.Results: Two siblings in this family presented with bilious vomiting, and were diagnosed with CSBS on laparotomy. Two siblings and their parents underwent complete exome sequencing of the peripheral blood. Both children had CLMP gene exons 3–5 homozygous deletion mutation, while the parents had a heterozygous mutation.Conclusion: This study identified a novel mutation of the CLMP gene in a Chinese family with CSBS. Identification of this mutation can help with genetic counseling and prenatal diagnosis of CSBS.

Three-dimensional (3D) topological insulator (TI) has emerged as a unique state of quantum matter and generated enormous interests in condensed matter physics. The surfaces of a 3D TI consist of a massless Dirac cone, which is characterized by the Z2 topological invariant. Introduction of magnetism on the surface of a TI is essential to realize the quantum anomalous Hall effect and other novel magneto-electric phenomena. Here, by using a combination of first-principles calculations, magneto-transport and angle-resolved photoemission spectroscopy (ARPES), we study the electronic properties of gadolinium (Gd)-doped Sb2Te3. Our study shows that Gd doped Sb2Te3 is a spin-orbit-induced bulk band-gap material, whose surface is characterized by a single topological surface state. Our results provide a new platform to investigate the interactions between dilute magnetism and topology in magnetic doped topological materials.

Quinones and quinone-containing organics have potential of activating persulfate to produce sulfate radical. In this work, the optimal condition for quinone activation of persulfate was investigated. It was found representative monoaromatics were degraded fastest in alkaline environment (pH 10.0), but excessive alkalinity restrained the reaction instead. The mechanisms to explain this phenomenon were speculated. The effect of initial quinone concentration on persulfate oxidation was also investigated at pH 10.0. In addition, a quantitative structure-activity relationship model was established with 15 kinds of monoaromatics, which revealed the most negative atomic net charges on carbon atom played an important role on degradation rates. Chemicals with a smaller qC- were easier oxidized in quinone-activate system. This finding helps further exploration of effective activator in alkaline environment.

Electron correlations play a central role in iron-based superconductors. In these systems, multiple Fe 3d-orbitals are active in the low-energy physics, and they are not all degenerate. For these reasons, the role of orbital-selective correlations has been an active topic in the study of the iron-based systems. In this article, we survey the recent developments on the subject. For the normal state, we emphasize the orbital-selective Mott physics that has been extensively studied, especially in the iron chalcogenides, in the case of electron filling n∼6. In addition, the interplay between orbital selectivity and electronic nematicity is addressed. For the superconducting state, we summarize the initial ideas for orbital-selective pairing and discuss the recent explosive activities along this direction. We close with some perspectives on several emerging topics. These include the evolution of the orbital-selective correlations, magnetic and nematic orders, and superconductivity as the electron filling factor is reduced from 6 to 5, as well as the interplay between electron correlations and topological band structure in iron-based superconductors.

Bacterial quorum sensing (QS) is a chemical communication that allows bacteria to coordinate their population and gene regulation in response to threshold concentrations of QS signals. Here, we study the effect of QS inhibitor 2(5H)-furanone (FUR) on the formation of Pseudoalteromonas marina ECSMB14103 biofilms and the effect of these biofilms on the settlement of plantigrades of the mussel Mytilus coruscus. FUR was added during biofilm formation of P. marina ECSMB14103 or in the settlement bioassay. FUR at 10–4 M added during biofilm formation significantly (p < 0.05) reduced the settlement of plantigrades, and it was associated with a significant (p < 0.05) reduction of bacterial density. The visualization of individual substances in biofilms shows that β-polysaccharides are the major components in the biofilm matrix. The decreased settlement rate may be attributed to the reduction of the biovolume of α-polysaccharides and β-polysaccharides in biofilms. The transcriptome of biofilms treated with 10–4 M FUR shows 61 genes are differentially expressed. Aspartate kinase and the flagellar assembly protein fliH gene are significantly affected after exposure to 10–4 M FUR (p < 0.05). They are involved in the synthesis of the bacterial cell wall and the mobility of bacteria, respectively. Exposure to 10–4 M FUR also significantly changes the carbapenem biosynthesis pathway, which is regulated by the QS system in bacteria (p < 0.05). These data suggest that FUR directly affects biofilm formation by altering extracellular polymeric substances (EPS) components and metabolic processes, which, in turn, indirectly reduce the settlement of plantigrades. The present study provides new insights into the molecular mechanisms of controlling biofouling.

The branched-chain amino acids (BCAAs) play a key role in the energy metabolism of the muscle tissue and the Krüppel-like factor 15 (KLF15) as a transcription factor, which is a key regulator of BCAA metabolism in the skeletal muscle. This study assessed the effect of starvation for 0, 3, 7, and 15 days on BCAA metabolism in the skeletal muscle of Nile tilapia. The results showed that the expression of KLF15 showed a trend of increasing first and then decreasing during starvation, as well as the expression and activity of branched-chain aminotransferase 2 (BCAT2) and alanine aminotransferase (ALT). On the other hand, the content of BCAA was at first decreased and then upregulated, and it reached the lowest level after starvation for 3 days. In addition, through dual-luciferase reporter assay and injection experiments, it was found that KLF15 is the target gene of miR-125a-3p, which further verified that miR-125a-3p can regulate the BCAA metabolism by targeting KLF15 in the skeletal muscle. Thus, our work investigated the possible mechanisms of BCAA metabolism adapting to nutritional deficiency in the skeletal muscle of Nile tilapia and illustrated the regulation of BCAA metabolism through the miR-125a-3p-KLF15-BCAA pathway in the skeletal muscle.

The microtubule-associated protein tau is closely correlated with hypometabolism in Alzheimer’s disease (AD). α-lipoic acid (LA), which is a naturally occurring cofactor in mitochondrial, has been shown to have properties that can inhibit the tau pathology and neuronal damage in our previous research. However, if LA affects glucose metabolism when it reverses tau pathology remains unclear, especially concerning the potential mechanism. Therefore, we make a further study using the P301S mouse model (a tauopathy and AD mouse model which overexpressing fibrillary tau) to gain a clear idea of the aforementioned problems. Here, we found chronic LA administration significantly increased glucose availability by elevating glucose transporter 3 (GLUT3), GLUT4, vascular endothelial growth factor (VEGF) protein and mRNA level, and heme oxygenase-1 (HO-1) protein level in P301S mouse brains. Meanwhile, we found that LA also promoted glycolysis by directly upregulating hexokinase (HK) activity, indirectly by increasing proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and DNA repair enzymes (OGG1/2 and MTH1). Further, we found the underlying mechanism of restored glucose metabolism might involve in the activation of brain-derived neurotrophic factor (BDNF)/tyrosine Kinase receptor B (TrkB)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway by LA treatment.

Isolated cerebral mucormycosis is a clinical type of mucormycosis that is estimated to account for 8% of all mucormycosis cases. The clinical symptoms of isolated cerebral mucormycosis are elusive, and thus conventional techniques often lake sensitivity and specificity. Moreover, cultures are often negative, even when direct microscopy examination is positive. Although histopathology will probably remain the gold standard for the diagnosis of mucormycosis, obtaining a biopsy specimen is not always feasible in most vulnerable populations. Thus, molecular approaches are currently used as an advantageous assistant examination method to improve the early identification of the causative agent and subsequently guide therapy to improve the prognosis of patients. Here, we report a case of isolated cerebral mucormycosis caused by Rhizopus microspores in a healthy young adult that was identified using next-generation sequencing technology.

Ischemic heart disease (IHD), caused predominantly by atherosclerosis, is a leading cause of global mortality. Our previous studies showed that Shenlian extract (SL) could prevent the formation of atherosclerosis and enhance the stability of atherosclerotic plaques. To further investigate the protective effects of SL on myocardial ischemic injury and its possible mechanisms, anesthetized dogs, ex vivo rat hearts, and H9c2 cardiomyocytes were used as models. The results showed that SL had a significant protective effect on the anesthetized dog ligating coronary artery model, reduced the degree of myocardial ischemia (Σ-ST), and reduced the scope of myocardial ischemia (N-ST). Meanwhile, SL alleviated ischemic reperfusion damage in ex vivo rat hearts with improved LVEDP and ± dp/dtmax values of the left ventricle. SL reduced the pathological changes of LDH, IL-1β, MDA, and NO contents, all of which are related to the expression of NF-κB. Further analysis by Bio-Plex array and signal pathway blocker revealed that the phosphorylation of IκB was a key factor for SL to inhibit myocardial ischemic injury, and the regulation of SL on IκB was primarily related to degradation of the IκB protein. These results provided dependable evidence that SL could protect against myocardial ischemic injury through the NF-κB signaling pathway.

Background: Lung adenocarcinoma is a common respiratory malignancy, however urethral metastasis of lung adenocarcinoma has not yet been reported. This study aims to present a rare case of isolated urethral metastasis in a male patient with a history of primary lung adenocarcinoma.Case Presentation: A 69 year-old male patient was admitted complaining of dysuria and nocturia for 3 months, with a history of lung adenocarcinoma after surgery. The patient was diagnosed as benign prostatic hyperplasia (BPH) and received holmium laser enucleation of the prostate, an effective transurethral procedure to treat bladder outflow obstruction due to BPH. Four months after surgery for BPH, the patient had no improvement in symptoms and continued to complain of dysuria and perineum pain. An MRI of the pelvis indicated posterior urethral mass without any regional lymphadenopathy or other sites of lesion. Urethrocystoscopy found the mass in the membranous urethra near the verumontanum, and pathology combined with immunohistochemical staining confirmed the isolated urethral metastasis of lung adenocarcinoma. The further therapeutic regimen consisting of chemotherapy (pemetrexed combined with nedaplatin) and bevacizumab was well-tolerated, and obviously relieved the patient from dysuria and perineum pain.Conclusion: This study reported the first case of isolated rare urethral metastasis from primary lung adenocarcinoma and underlined the necessity for clinicians to remain vigilant to metastasis during follow-up of primary cancer.

Background: Different proportions of Gleason pattern 3 and Gleason pattern 4 lead to various prognosis of prostate cancer with Gleason score 7. The objective of this study was to compare the survival outcomes of Gleason score 3+4 and 4+3 based on data from the Surveillance, Epidemiology, and End Results cancer registry database, and to investigate independent prognosis-associated factors and develop nomograms for predicting survival in Gleason score 7 prostate cancer patients.Methods: A retrospective study was conducted on 69,116 cases diagnosed as prostate adenocarcinoma with Gleason score 7 between 2004 and 2009. Prognosis-associated factors were evaluated using univariate and multivariate Cox regression analysis, and a 1:1 ratio paired cohort by propensity score matching with the statistical software IBM SPSS, to evaluate prognostic differences between Gleason score 3+4 and 4+3. The primary cohort was randomly divided into training set (n = 48,384) and validation set (n = 20,732). Based on the independent factors of prognosis, nomograms for prognosis were established by the training group and validated by the validation group using R version 3.5.0.Results: After propensity score matching, Cox regression analysis showed that Gleason 4+3 had an increased mortality risk both for overall survival (HR: 1.235, 95% CI: 1.179–1.294, P < 0.001) and cancer-specific survival (HR: 1.606, 95% CI: 1.468–1.762, P < 0.001). Nomograms for overall survival and cancer-specific survival were established with C-index 0.786 and 0.842, respectively. The calibration plot indicated an optimal agreement between the actual observation and nomogram prediction for overall survival and cancer-specific survival probability at 5 or 10 year.Conclusions: Prostate cancer with Gleason score 4+3 had worse overall survival and cancer-specific survival than Gleason score 3+4. Nomograms were formulated to predict 5-year and 10-year OS and CSS in patients with prostate cancer of Gleason score 7.

The Sino-Japanese Floristic Region (SJFR) is a key area for plant phylogeographical research, due to its very high species diversity and disjunct distributions of a large number of species and genera. At present, the root cause and temporal origin of the discontinuous distribution of many plants in the Sino-Japanese flora are still unclear. Diabelia (Caprifoliaceae; Linnaeoideae) is a genus endemic to Asia, mostly in Japan, but two recent discoveries in China raised questions over the role of the East China Sea (ECS) in these species' disjunctions. Chloroplast DNA sequence data were generated from 402 population samples for two regions (rpl32-trnL, and trnH-psbA) and 11 nuclear microsatellite loci were screened for 549 individuals. Haplotype, population-level structure, combined analyses of ecological niche modeling, and reconstruction of ancestral state in phylogenies were also performed. During the Last Glacial Maximum (LGM) period after the Tertiary, Diabelia was potentially widely distributed in southeastern China, the continental shelf of the East China Sea and Japan (excluding Hokkaido). After LGM, all populations in China have disappeared except those in Zhejiang which may represent a Glacial refuge. Populations of Diabelia in Japan have not experienced significant bottleneck effects, and populations have maintained a relatively stable state. The observed discontinuous distribution of Diabelia species between China and Japan are interpreted as the result of relatively ancient divergence. The phylogenetic tree of chloroplast fragments shows the characteristics of multi-origin evolution (except for D. sanguinea). STRUCTURE analysis of nuclear Simple Sequence Repeat (nSSR) showed that the plants of the Diabelia were divided into five gene pools: D. serrata, D. spathulata, D. sanguinea, D. ionostachya (D. spathulata var. spathulata-Korea), and populations of D. ionostachya var. ionostachya in Yamagata prefecture, northern Japan. Molecular evidence provides new insights of Diabelia into biogeography, a potential glacial refuge, and population-level genetic structure within species. In the process of species differentiation, ECS acts as a corridor for two-way migration of animals and plants between China and Japan during glacial maxima, providing the possibility of secondary contact for discontinuously distributed species between China and Japan, or as a filter (creating isolation) during glacial minima. The influence of the ECS in speciation and biogeography of Diabelia in the Tertiary remains unresolved in this study. Understanding origins, evolutionary histories, and speciation will provide a framework for the conservation and cultivation of Diabelia.

As a novel gasotransmitter, hydrogen sulfide (H2S) elicits various physiological actions including smooth muscle relaxation and promotion of transepithelial ion transport. However, the pro-secretory function of H2S in the male reproductive system remains largely unclear. The aim of this study is to elucidate the possible roles of H2S in modulating rat epididymal intraluminal ionic microenvironment essential for sperm storage. The results revealed that endogenous H2S-generating enzymes cystathionine β-synthetase (CBS) and cystathionine γ-lyase (CSE) were both expressed in rat epididymis. CBS located predominantly in epithelial cells whilst CSE expressed primarily in smooth muscle cells. The relative expression level of CBS and CSE escalated from caput to cauda regions of epididymis, which was paralleled to the progressively increasing production of endogenous H2S. The effect of H2S on epididymal epithelial ion transportation was investigated using short-circuit current (ISC), measurement of intracellular ion concentration and in vivo rat epididymal microperfusion. Our data showed that H2S induced transepithelial K+ secretion via adenosine triphosphate-sensitive K+ (KATP) channel and large conductance Ca2+-activated K+ (BKCa) channel. Transient receptor potential vanilloid 4 (TRPV4) channel-mediated Ca2+ influx was implicated in the activation of BKCa channel. In vivo studies further demonstrated that H2S promoted K+ secretion in rat epididymal epithelium. Inhibition of endogenous H2S synthesis caused a significant decrease in K+ concentration of cauda epididymal intraluminal fluid. Moreover, our data demonstrated that high extracellular K+ concentration actively depressed the motility of cauda epididymal sperm in a pH-independent manner. Collectively, the present study demonstrated that H2S was vital to the formation of high K+ concentration in epididymal intraluminal fluid by promoting the transepithelial K+ secretion, which might contribute to the maintenance of the cauda epididymal sperm in quiescent dormant state before ejaculation.