Single nucleus DNA sequencing of flow sorted archived frozen and formalin fixed paraffin embedded solid tumors.

BACKGROUND: Archived samples, including frozen and formalin fixed paraffin embedded (FFPE) tissues, are a vast resource of clinically annotated materials for the application of high-definition genomics to improve patient management and provide a molecular basis for the delivery of personalized cancer therapeutics. Notably, FFPE tissues are stable, provide repeat sampling of tissues of interest, and can be stored indefinitely at ambient temperature. The development of single cell DNA sequencing (scDNA-seq) technologies provides an unparalleled opportunity for the study of tumor heterogeneity and the identification of often rare subclonal cell populations that drive tumor evolution and progression to advanced therapy resistant disease. However, major limitations to the use of archived tissues for scDNA-seq include the low yields of intact cells in the presence of high levels of subcellular debris in biopsies, and the highly variable quantity and quality of the DNA extracted from samples of interest. The latter is of high significance for the use of FFPE tissues due to the presence of DNA-protein crosslinks. In addition, many samples, notably tumors arising in solid tissues, contain admixtures of reactive stroma, inflammatory cells, and necrosis in immediate contact with tumor cells. RESULTS: To expand their use for translational studies, we optimized flow sorting and sequencing of single nuclei from archived fresh frozen (FF) and FFPE tumor tissues. Our methods, which include isolation of intact nuclei suitable for library preparations, quality control (QC) metrics for each step, and a single cell sequencing bioinformatic processing and analysis pipeline, were validated with flow sorted nuclei from matching FF and FFPE ovarian cancer surgical samples and a sequencing panel of 553 amplicons targeting single nucleotide and copy number variants in genes of interest. CONCLUSIONS: Our flow sorting based protocol provides intact nuclei suitable for snDNA-seq from archival FF and FFPE tissues. Furthermore, we have developed QC steps that optimize the preparation and selection of samples for deep single cell clonal profiling. Our data processing pipeline captures rare subclones in tumors with highly variable genomes based on variants in genes of interest.

Noise-Aware Active Learning to Develop High-Temperature Shape Memory Alloys with Large Latent Heat.

Shape memory alloys (SMAs) with large latent heat absorbed/released during phase transformation at elevated temperatures benefit their potential application on thermal energy storage (TES) in high temperature environment like power plants, etc. The desired alloys can be designed quickly by searching the vast component space of doped NiTi-based SMAs via data-driven method, while be challenging with the noisy experimental data. A noise-aware active learning strategy is proposed to accelerate the design of SMAs with large latent heat at elevated phase transformation temperatures based on noisy data. The optimal noise level is estimated by minimizing the model error with incorporation of a range of noise levels as noise hyper-parameters into the noise-aware Kriging model. The employment of this strategy leads to the discovery of the alloy with latent heat of -36.08 J g-1, 9.2% larger than the best value (-33.04 J g-1) in the original training dataset within another four experiments. Additionally, the alloy represents high austenite finish temperature (481.71°C) and relatively small hysteresis. This promotes the latent heat TES application of SMAs in high temperature circumstance. It is expected that the noise-aware approach can be convenient for the accelerated materials design via the data-driven method with noisy data.

Comparative genomic analysis of Acanthamoeba from different sources and horizontal transfer events of antimicrobial resistance genes.

Acanthamoeba species are among the most common free-living amoeba and ubiquitous protozoa, mainly distributed in water and soil, and cause Acanthamoeba keratitis (AK) and severe visual impairment in patients. Although several studies have reported genomic characteristics of Acanthamoeba, limited sample sizes and sources have resulted in an incomplete understanding of the genetic diversity of Acanthamoeba from different sources. While endosymbionts exert a significant influence on the phenotypes of Acanthamoeba, including pathogenicity, virulence, and drug resistance, the species diversity and functional characterization remain largely unexplored. Herein, our study sequenced and analyzed the whole genomes of 19 Acanthamoeba pathogenic strains that cause AK, and by integrating publicly available genomes, we sampled 29 Acanthamoeba strains from ocular, environmental, and other sources. Combined pan-genomic and comparative functional analyses revealed genetic differences and evolutionary relationships among the different sources of Acanthamoeba, as well as classification into multiple functional groups, with ocular isolates in particular showing significant differences that may account for differences in pathogenicity. Phylogenetic and rhizome gene mosaic analyses of ocular Acanthamoeba strains suggested that genomic exchanges between Acanthamoeba and endosymbionts, particularly potential antimicrobial resistance genes trafficking including the adeF, amrA, and amrB genes exchange events, potentially contribute to Acanthamoeba drug resistance. In conclusion, this study elucidated the adaptation of Acanthamoeba to different ecological niches and the influence of gene exchange on the evolution of ocular Acanthamoeba genome, guiding the clinical diagnosis and treatment of AK and laying a theoretical groundwork for developing novel therapeutic approaches. IMPORTANCE: Acanthamoeba causes a serious blinding keratopathy, Acanthamoeba keratitis, which is currently under-recognized by clinicians. In this study, we analyzed 48 strains of Acanthamoeba using a whole-genome approach, revealing differences in pathogenicity and function between strains of different origins. Horizontal transfer events of antimicrobial resistance genes can help provide guidance as potential biomarkers for the treatment of specific Acanthamoeba keratitis cases.

The balance between alleviating copper damage and maintaining root function during root pruning with excessive copper.

Coating high concentrations of copper (Cu) on the inner wall of containers can efficiently inhibit root entanglement of container-grown seedlings. However, how the protective and defensive responses of roots maintain root structure and function during Cu-root pruning is still unclear. Here, Duranta erecta seedlings were planted in the containers coated with 40 (T1), 80 (T2), 100 (T3), 120 (T4), 140 (T5), and 160 (T6) g L-1 Cu(OH)2 with containers without Cu(OH)2 as the control. Although T5 and T6 produced the best inhibitory effect on root entanglement, root anatomy structure was damaged. T1 and T2 not only failed to completely control root circling, but also led to decreased root activity and stunted growth. Cu(OH)2 treatments significantly increased lignin concentration of roots with the highest values at T3 and T4. Compared with T3, seedlings at T4 had higher height, biomass, and root activity and no significant root entanglement. Excessive Cu accumulation in Cu(OH)2 treatments changed the absorption of other mineral nutrients and their allocation in the roots, stems, and leaves. Overall, Ca was decreased while Mg, Mn, Fe, and K were increased, especially K and Mn at T4 which is related to defense capacity. The results indicate that there is a Cu threshold to balance root entanglement control, defense capacity, and nutrient uptake function under excessive Cu for container-grown D. erecta seedlings.

A nomogram-based prediction model for dysphagia in patients with chronic obstructive pulmonary disease: A cross-sectional study.

AIM AND OBJECTIVES: To investigate the prevalence of dysphagia in patients with COPD, identify the risk factors for dysphagia, develop a visual clinical prediction model and quantitatively predict the probability of developing dysphagia. BACKGROUND: Patients with COPD are at high risk of dysphagia, which is strongly linked to the acute exacerbation of their condition. The use of effective tools to predict its risk may contribute to the early identification and treatment of dysphagia in patients with COPD. DESIGN: A cross-sectional design. METHODS: From July 2021 to April 2023, we enrolled 405 patients with COPD for this study. The clinical prediction model was constructed according to the results of a univariate analysis and a logistic regression analysis, evaluated by discrimination, calibration and decision curve analysis and visualized by a nomogram. This study was reported using the TRIPOD checklist. RESULTS: In total, 405 patients with COPD experienced dysphagia with a prevalence of 59.01%. A visual prediction model was constructed based on age, whether combined with cerebrovascular disease, chronic pulmonary heart disease, acute exacerbation of COPD, home noninvasive positive pressure ventilation, dyspnoea level and xerostomia level. The model exhibited excellent discrimination at an AUC of .879. Calibration curve analysis indicated a good agreement between experimental and predicted values, and the decision curve analysis showed a high clinical utility. CONCLUSION: The model we devised may be used in clinical settings to predict the occurrence of dysphagia in patients with COPD at an early stage. RELEVANCE TO CLINICAL PRACTICE: The model can help nursing staff to calculate the risk probability of dysphagia in patients with COPD, formulate personalized preventive care measures for high-risk groups as soon as possible to achieve early prevention or delay of dysphagia and its related complications and improve the prognosis. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Genomic landscape of diploid and aneuploid microsatellite stable early onset colorectal cancer.

Although colorectal cancer (CRC) remains the second leading cause of cancer-related death in the United States, the overall incidence and mortality from the disease have declined in recent decades. In contrast, there has been a steady increase in the incidence of CRC in individuals under 50 years of age. Hereditary syndromes contribute disproportionately to early onset CRC (EOCRC). These include microsatellite instability high (MSI+) tumors arising in patients with Lynch Syndrome. However, most EOCRCs are not associated with familial syndromes or MSI+ genotypes. Comprehensive genomic profiling has provided the basis of improved more personalized treatments for older CRC patients. However, less is known about the basis of sporadic EOCRC. To define the genomic landscape of EOCRC we used DNA content flow sorting to isolate diploid and aneuploid tumor fractions from 21 non-hereditary cases. We then generated whole exome mutational profiles for each case and whole genome copy number, telomere length, and EGFR immunohistochemistry (IHC) analyses on subsets of samples. These results discriminate the molecular features of diploid and aneuploid EOCRC and provide a basis for larger population-based studies and the development of effective strategies to monitor and treat this emerging disease.

The Safety and Efficacy of Remimazolam Compared to Dexmedetomidine for Awake Tracheal Intubation by Flexible Bronchoscopy: A Randomized, Double-Blind, Controlled Trial.

Background: Remimazolam is a novel ultra-short-acting benzodiazepine sedative that has the potential to be an alternative for procedural sedation due to its rapid sedation and recovery, no accumulation effect, stable hemodynamics, minimal respiratory depression, anterograde amnesia effect, and specific antagonist. Here, we aimed to compare the safety and efficacy of remimazolam with dexmedetomidine for awake tracheal intubation by flexible bronchoscopy (ATI-FB). Methods: Ninety patients scheduled for ATI-FB were randomly divided into three groups, each consisting of 30 cases: dexmedetomidine 0.6 µg/kg + sufentanil (group DS), remimazolam 0.073 mg/kg + sufentanil (group R1S), or remimazolam 0.093 mg/kg + sufentanil (group R2S). The primary outcome was the success rate of sedation. Secondary outcomes were MOAA/S scores, hemodynamic and respiratory parameters, intubation conditions, intubation time, tracheal intubation amnesia, and adverse events. Results: The success rates of sedation in groups R2S and DS were higher than that in group R1S (93.3%, 86.7%, respectively, vs 58.6%; P = 0.002), and intubation conditions were better than those in group R1S (P < 0.05). Group R2S had shorter intubation times than groups R1S and DS (P = 0.003), and a higher incidence of tracheal intubation amnesia than group DS (P = 0.006). No patient in the three groups developed hypoxemia or hypotension, and there were no significant differences in oligopnea, PetCO2, or bradycardia (P > 0.05). Conclusion: In conclusion, both DS and R2S had higher success rates of sedation, better intubation conditions, and minor respiratory depression, but R2S, with its shorter intubation time, higher incidence of anterograde amnesia, and ability to be antagonized by specific antagonists, may be a good alternative sedation regimen for patients undergoing ATI-FB.

Validity and reliability of the toxic leadership behaviors of nurse managers scale among Chinese nurses.

Objectives: Toxic leadership is increasingly becoming common in the nursing field, but the measurement tools are lacking. Therefore, this study aimed to translate the toxic leadership behaviors of nurse managers (ToxBH-NM) scale into Chinese and test its psychometric properties among Chinese nurses. Methods: The data for this study were obtained from a cross-sectional survey of 1,195 nurses. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to examine the structural validity of the ToxBH-NM. The following psychometric properties of the scale were assessed: content validity, criterion validity, internal consistency reliability, and test-retest reliability. Results: The Chinese version of the ToxBH-NM (C-ToxBH-NM) scale had two dimensions and 30 items. The correlation coefficients between the scores of each item and the total scores were 0762-0.922 (p < 0.001), and the range of the CR determination values of all the items were 8.610-18.998, with statistical significance (p < 0.001). The total content validity index (CVI) was 0.996, the average CVI was 0.996, and the item-level CVI was 0.875-1.000. Two common factors were identified in the EFA, and 81.074% of the variation was explained cumulatively. The CFA showed that all the fitting indexes reached the standard, and the model fit degree was good. When the Chinese version of the Destructive Leadership Scale was used as calibration, the correlation coefficient was 0.378 (p < 0.001). The Cronbach's alpha coefficients of the overall scale were 0.989 and of the two dimensions were 0.969 and 0.987, respectively, with a split-half reliability of 0.966 and test-retest reliability of 0.978. Conclusion: The research results show that the C-ToxBH-NM scale has good reliability and validity and can be used to evaluate the severity of toxic leadership behavior among nursing managers.

Patient-Derived Tumor Xenograft Study with CDK4/6 Inhibitor Plus AKT Inhibitor for the Management of Metastatic Castration-Resistant Prostate Cancer.

Metastatic castration-resistant prostate cancer (mCRPC) is an aggressive malignancy with poor outcomes. To investigate novel therapeutic strategies, we characterized three new metastatic prostate cancer patient derived-tumor xenograft (PDTX) models and developed 3D spheroids from each to investigate molecular targeted therapy combinations including CDK4/6 inhibitors (CDK4/6i) with AKT inhibitors (ATKi). Metastatic prostate cancer tissue was collected and three PDTX models were established and characterized using whole-exome sequencing. PDTX 3D spheroids were developed from these three PDTXs to show resistance patterns and test novel molecular-targeted therapies. CDK4/6i's were combined with AKTi's to assess synergistic antitumor response to prove our hypothesis that blockade of AKT overcomes drug resistance to CDK4/6i. This combination was evaluated in PDTX three-dimensional (3D) spheroids and in vivo experiments with responses measured by tumor volumes, PSA, and Ga-68 PSMA-11 PET-CT imaging. We demonstrated CDK4/6i's with AKTi's possess synergistic antitumor activity in three mCRPC PDTX models. These models have multiple unique pathogenic and deleterious genomic alterations with resistance to single-agent CDK4/6i's. Despite this, combination therapy with AKTi's was able to overcome resistance mechanisms. The IHC and Western blot analysis confirmed on target effects, whereas tumor volume, serum PSA ELISA, and radionuclide imaging demonstrated response to therapy with statistically significant SUV differences seen with Ga-68 PSMA-11 PET-CT. These preclinical data demonstrating antitumor synergy by overcoming single-agent CDK 4/6i as well as AKTi drug resistance provide the rational for a clinical trial combining a CDK4/6i with an AKTi in patients with mCRPC whose tumor expresses wild-type retinoblastoma 1.

IGF-1 Regulates Skeletal Muscle Degradation and Remolding in Ventilator-Induced Diaphragmatic Dysfunction by Mediating FOXO1 Expression.

BACKGROUND: Mechanical ventilation (MV) sustains life in critically ill patients by providing adequate alveolar ventilation. However, prolonged MV could induce inspiratory muscle atrophy known as ventilator-induced diaphragmatic dysfunction (VIDD). Insulin-like growth factor (IGF)-1 has been proven to play crucial roles in regulating skeletal muscle size and function. Meanwhile, the forkhead box protein O1 (FOXO1) has been linked to muscle atrophy. This study aimed to explore the effect of IGF-1 on muscle degradation and remodeling in VIDD and delved into the association of the underlying mechanism involving FOXO1. METHODS: VIDD models were established by treating rats with MV. Adeno-associated virus (AAV) was used for transfection to construct IGF-1 and/or FOXO1 overexpressed rats. There were four groups in this study: normal rats (NC), normal rats with MV treatment (MV), IGF-1-overexpressed rats with MV treatment (MV+IGF-1), and rats overexpressing both IGF-1 and FOXO1 with MV treatment (MV+IGF-1+FOXO1). Protein levels were measured by western blot or enzyme-linked immunosorbent assay (ELISA), and mRNA levels were detected by real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). IGF-1 and FOXO1 expression were validated by detecting mRNA and protein levels. Diaphragmatic muscle contractility and morphometry were tested using stimulating electrodes in conjunction with hematoxylin and eosin (H&E) staining. Interleukin (IL)-6 and carbonylated protein were used for evaluating muscle atrophy and oxidation, respectively. Protein degradation was determined by troponin-I level and tyrosine release. Apoptosis was assessed using the terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate (UTP) nick-end labeling (TUNEL) assay, alongside markers like Bax, B-cell lymphoma 2 (BCL-2), and Cleaved Caspase-3. Atrogin-1, muscle RING finger 1 (MURF1), neuronally expressed developmentally downregulated 4 (NEDD4), muscle ubiquitin ligase of SCF complex in atrophy-1 (MUSA1), and ubiquitinated protein was used to determine proteolysis. Additionally, protein synthesis was measured by assessing the rates of mixed muscle protein (MMP) and myosin heavy chain (MHC). RESULTS: MV treatment caused IGF-1 downregulation (p < 0.01) and FOXO1 upregulation (p < 0.01). The IGF-1 upregulation downregulated FOXO1 in the MV+IGF-1 group (p < 0.001) while IGF-1 and FOXO1 were both upregulated in the MV+IGF-1+FOXO1 group (p < 0.001). The treatment of MV decreased muscle contractility and cross-sectional areas of diaphragm muscle fibers (p < 0.01). Additionally, IL-6, troponin-1, tyrosine release, carbonylated protein, TUNEL positive nuclei, Bax, Cleaved Caspase-3, Atrogin-1, MURF1, neuronally expressed developmentally downregulated 4 (NEDD4), MUSA1, and ubiquitinated protein levels increased significantly in MV group (p < 0.001) while levels of BCL-2, fractional synthetic rate of MMP and MHC, and type I and type II MHC protein mRNA expression decreased in MV group (p < 0.001). All of these alterations were reversed in the MV+IGF-1 group (p < 0.01), while the IGF-1-induced reversion was disrupted in the MV+IGF-1+FOXO1 group (p < 0.01). CONCLUSIONS: IGF-1 may protect diaphragmatic muscles from VIDD-induced structural damage and function loss by downregulating FOXO1. This action suppresses muscle breakdown and facilitates muscle remodeling in diaphragmatic muscles affected by VIDD.

Event-triggered impulsive quasi-synchronization for BAM neural networks with reliable redundant channel.

This work addresses the quasi-synchronization of delay master-slave BAM neural networks. To improve the utilization of channel bandwidth, a dynamic event-triggered impulsive mechanism is employed, in which data is transmitted only when a preset event-triggered mechanism or a forced impulse interval is satisfied. In addition, to guarantee the reliability of information transmission, a reliable redundant channel for BAM neural networks is adopted, whose transmission scheduling strategy is designed on the basis of the packet dropouts rate of the main communication channels. Further, an algorithm is employed to reduce the quasi-synchronization range of the error systems and the controllers are obtained. At last, a simulation result is shown to illustrate the effectiveness of the presented strategy.

Screening the optimal housekeeping genes (HKGs) of placenta tissues by RNA-sequence and qRT-PCR throughout gestation in goat (Capra Hircus).

Selection of stable housekeeping genes (HKGs) is very important for accurate calculation of relative expression levels of target genes by quantitative real-time polymerase chain reaction (qRT-PCR). At present, the appropriate HKGs have not been identified in placental tissues throughout the pregnancy of the goat. In our study, 20 HKGs were tentatively selected from RNA-seq data and previous reports. The cycle threshold (Ct) of HKGs was determined by qRT-PCR in trophoblast membrane and cotyledon villus collected from 38 Dazu Black goats on gestation days of 20, 25, 30, 45, 60, 90, 120, and 150 (birth). The expression stability of the HKGs was analyzed by geNorm, Normfinder, Bestkeeper and Delta Ct algorithms, and comprehensively evaluated by ReFinder and ComprFinder. In addition, the optimal HKGs were further verified by placenta-specific genes (SPP1, VEGFA and PAG6). The 16 candidate HKGs (except POP4, TBP, RNF10, UBC) showed a qualified Ct value, less than 28. Among them, YWHAZ, EIF3K and PPIB showed the most stable expression in placental tissues during early, mid-late pregnancy and postpartum, but the least stable expression was B2M at early and mid-late stage, and PPIB at postpartum. After comprehensive analysis, RPLP0, EIF3K and YWHAZ were found to be the most stable placental HKGs throughout pregnancy. The classical HKGs, ACTB, GAPDH and 18S RNA have unstable expressions and even ranked at the bottom of the list from comprehensive index, suggesting an inappropriate for target gene normalization. Taken together, our study confirmed that YWHAZ, EIF3K, HMBS and RPLP0 may be the optimal HKGs in goat placenta at different stage of pregnancy, which provided a valuable reference of HKGs on functional gene expression detection for further research on placenta development and growth in ruminants.

Fecal microbiota as a predictor of acupuncture responses in patients with postpartum depressive disorder.

Background: There are several clinical and molecular predictors of responses to antidepressant therapy. However, these markers are either too subjective or complex for clinical use. The gut microbiota could provide an easily accessible set of biomarkers to predict therapeutic efficacy, but its value in predicting therapy responses to acupuncture in patients with depression is unknown. Here we analyzed the predictive value of the gut microbiota in patients with postpartum depressive disorder (PPD) treated with acupuncture. Methods: Seventy-nine PPD patients were enrolled: 55 were treated with acupuncture and 24 did not received any treatment. The 17-item Hamilton depression rating scale (HAMD-17) was used to assess patients at baseline and after eight weeks. Patients receiving acupuncture treatment were divided into an acupuncture-responsive group or non-responsive group according to HAMD-17 scores changes. Baseline fecal samples were obtained from the patients receiving acupuncture and were analyzed by high-throughput 16S ribosomal RNA sequencing to characterize the gut microbiome. Results: 47.27% patients responded to acupuncture treatment and 12.5% patients with no treatment recovered after 8-week follow-up. There was no significant difference in α-diversity between responders and non-responders. The ß-diversity of non-responders was significantly higher than responders. Paraprevotella and Desulfovibrio spp. were significantly enriched in acupuncture responders, and these organisms had an area under the curve of 0.76 and 0.66 for predicting responder patients, respectively. Conclusions: Paraprevotella and Desulfovibrioare may be useful predictive biomarkers to predict PPD patients likely to respond to acupuncture. Larger studies and validation in independent cohorts are now needed to validate our findings.

Peripheral Blood Inflammatory Cytokine Factors Expressions are Associated with Response to Acupuncture Therapy in Postpartum Depression Patients.

Background: Increasing evidences demonstrate that immune dysregulation can result in depression, and it is reported that persistent inflammatory response is related to the unresponsiveness of antidepressant treatment. Purpose: This study aimed to explore the reason why some responded but some not responded to acupuncture in treating postpartum depression (PPD), and whether it related to the levels of inflammatory cytokines. Patients and Methods: Women diagnosed with PPD were recruited in to accept 8-week acupuncture. All subjects were assessed the 17-item Hamilton Depression Rating Scale (HDRS17) at baseline, week 1, week 2, week 4 and week 8 during the treatment. A panel of 9 cytokines was measured at baseline and 8 weeks. Results: Of the 121 participants, 96 completed the 8-week assessment and 46 completed the blood sample collection. HDRS17 scores of 96 subjects showed significant statistical reduction since the first week (P = 0.002) and reached to 5.31 (P < 0.000) at the end of therapy. And we divided the 46 subjects into responders and non-responders according to the response rate of HDRS17 scores. Responders and non-responders did not differ significantly between-group in changes in the 9 cytokines. In responders, IL-6, IL-10 and IFN-γ levels were statistically lower (P = 0.006; P = 0.033; P = 0.024), while TGF-ß1 was statistically higher after 8 weeks treatment (P < 0.000). In non-responders, the levels of IL-5, TNF-α and TGF-ß1 were statistically higher (P = 0.018; P < 0.000; P < 0.000), while IFN-γ was statistically lower (P = 0.005). Conclusion: Acupuncture could alleviate depressive symptoms of patients with PPD and might through adjusting peripheral inflammatory response by up-regulating anti-inflammatory cytokines and down-regulating pro-inflammatory cytokines.

Impact of carotid hemodynamics on carotid plaque location: Age difference.

PURPOSE: This study was aimed to investigate the influence of carotid hemodynamics in common carotid artery (CCA) and internal carotid artery (ICA) on carotid plaque location. METHODS: A total of 4444 participants from Anhui Maanshan People's Hospital were selected from December 2013 to December 2018. Doppler ultrasound was used to measure the location of carotid plaque. Patients were divided into four groups according to plaque location: LEFT, RIGHT, BOTH, and NONE. Multiple logistic regression and smooth curve were applied to determine the relationship of carotid plaque location and hemodynamic indexes. RESULTS: Compared with the NONE group, the ratio of artery systolic and diastolic blood flow velocity in right internal carotid (RICA S/D) was a risk factor for LEFT group (OR=1.548) after adjustment; artery systolic and diastolic blood flow velocity ratio of left common carotid artery (LCCA S/D) was a risk factor for RIGHT group (OR=1.250); resistance index of right internal carotid (RICA RI) was a protective factor for BOTH group (OR=0.097), while LCCA S/D and RICA S/D were risk factors for BOTH group (OR=1.201, OR=1.457). Compared with the RIGHT group, artery systolic and diastolic blood flow velocity ratio of right common carotid (RCCA S/D) was the risk factor for the LEFT group (OR=1.463), LCCA S/D and RICA S/D were the risk factors for BOTH group (OR=1.706, OR=2.111). After age stratification, resistance index of right common carotid artery (RCCA RI) and resistance index of left internal carotid artery (LICA RI) were protective factors for BOTH group (OR=0.046, OR=0.042) in group younger than 52. RCCA S/D and RICA S/D were risk factors for BOTH group (OR=1.557, OR=1.843). Resistance index of left common carotid artery (LCCA RI) was a protective factor in the LEFT group compared with the RIGHT group (OR=0.476). In group older than 52, RICA S/D was a risk factor for LEFT group (OR=1.388). LCCA S/D was a risk factor for RIGHT group (OR=1.575). LCCA S/D and RICA S/D were risk factors for BOTH group (OR=1.348, OR=1.311). RICA S/D and RCCA S/D were protective factors in the LEFT group compared with the RIGHT group (OR=0.567, OR=0.680).

Beaded CoSe2-C Nanofibers for High-Performance Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries are regarded as highly promising energy storage devices due to their high theoretical specific capacity and high energy density. Nevertheless, the commercial application of Li-S batteries is still restricted by poor electrochemical performance. Herein, beaded nanofibers (BNFs) consisting of carbon and CoSe2 nanoparticles (CoSe2/C BNFs) were prepared by electrospinning combined with carbonization and selenization. Benefitting from the synergistic effect of physical adsorption and chemical catalysis, the CoSe2/C BNFs can effectively inhibit the shuttle effect of lithium polysulfides and improve the rate performance and cycle stability of Li-S batteries. The three-dimensional conductive network provides a fast electron and ion transport pathway as well as sufficient space for alleviating the volume change. CoSe2 can not only effectively adsorb the lithium polysulfides but also accelerate their conversion reaction. The CoSe2/C BNFs-S cathode has a high reversible discharge specific capacity of 919.2 mAh g-1 at 0.1 C and presents excellent cycle stability with a low-capacity decay rate of 0.05% per cycle for 600 cycles at 1 C. The combination of the beaded carbon nanofibers and polar metal selenides sheds light on designing high-performance sulfur-based cathodes.

Structural and functional improvement of amygdala sub-regions in postpartum depression after acupuncture.

Objective: This study aimed to analyze the changes in structure and function in amygdala sub-regions in patients with postpartum depression (PPD) before and after acupuncture. Methods: A total of 52 patients with PPD (All-PPD group) were included in this trial, 22 of which completed 8 weeks of acupuncture treatment (Acu-PPD group). An age-matched control group of 24 healthy postpartum women (HPW) from the hospital and community were also included. Results from the 17-Hamilton Depression Scale (17-HAMD) and the Edinburgh Postnatal Depression Scale (EPDS) were evaluated, and resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed at baseline and after the acupuncture treatment. Sub-regions of the amygdala were used as seed regions to measure gray matter volume (GMV) and analyzed for resting-state functional connectivity (RSFC) values separately. Finally, correlation analyses were performed on all patients with PPD to evaluate association values between the clinical scale scores, GMV, and RSFC values, while controlling for age and education. Pearson's correlation analyses were conducted to investigate the relevance between GMV and RSFC values of brain regions that differed before and after acupuncture treatment and clinical scale scores in Acu-PPD patients. Results: The HAMD scores for Acu-PPD were reduced after acupuncture treatment (P < 0.05), suggesting the positive effects of acupuncture on depression symptoms. Structurally, the All-PPD group showed significantly decreased GMV in the left lateral part of the amygdala (lAMG.L) and the right lateral part of the amygdala (lAMG.R) compared to the HPW group (P < 0.05). In addition, the GMV of lAMG.R was marginally increased in the Acu-PPD group after acupuncture (P < 0.05). Functionally, the Acu-PPD group showed a significantly enhanced RSFC between the left medial part of the amygdala (mAMG.L) and the left vermis_6, an increased RSFC between the right medial part of the amygdala (mAMG.R) and left vermis_6, and an increased RSFC between the lAMG.R and left cerebelum_crus1 (P < 0.05). Moreover, correlation studies revealed that the GMV in the lAMG.R was significantly related to the EPDS scores in the All-PPD group (P < 0.05). Conclusion: Our findings demonstrated that the structure of amygdala sub-regions is impaired in patients with PPD. Acupuncture may improve depressive symptoms in patients with PPD, and the mechanism may be attributed to changes in the amygdala sub-region structure and the functional connections of brain areas linked to the processing of negative emotions. The fMRI-based technique can provide comprehensive neuroimaging evidence to visualize the central mechanism of action of acupuncture in PPD.

Screening of Candidate Housekeeping Genes in Uterus Caruncle by RNA-Sequence and qPCR Analyses in Different Stages of Goat (Capra hircus).

The uterus is a critical pregnancy organ for mammals. The normal growth and development of ruminant uterus caruncles are crucial to maintain gestation and fetal health in goats. Quantitative real-time polymerase chain reaction (qRT-PCR) is a reliable tool to study gene expression profiling for exploring the intrinsic mechanism underlying the conversion process of uterus caruncle tissue. However, the candidate housekeeping genes (HKGs) are required for normalizing the expression of function genes. In our study, 22 HKGs were selected from analyzing transcriptome data at non-pregnancy and pregnancy processes and previous reports about HKGs in goat tissues. We assessed them for expression suitability in 24 samples from uterus tissues at 15 non-pregnant days (Stage 1), early (Stage 2), and medium-later pregnant days (Stage 3). The expression stability of these genes was evaluated by using geNorm, Normfinder, Bestkeeper, and Delta Ct algorithms and, comprehensively, by ReFinder. In addition, the most and least stable HKGs were used to normalize the target genes expression of SPP1, VEGFA, and PAG8. It was found that traditional reference genes, such as ACTB and GAPDH, were not suitable for target gene normalization. In contrast, PPIB selected from RNA sequencing data and EIF3K selected from previous references showed the least variation and were recommended as the best HKGs during the nonpregnant stage and the whole stages of goat uterus caruncle tissue, respectively. It is the first time the HKGs genes in uterus during the non-pregnant day and throughout the total pregnancy have been explored. These findings found suitable HKGs in uterus caruncle tissues at various stages of non-pregnancy and pregnancy; these can be useful for gene expression studies to reveal the molecular mechanisms of uterus development in goats.

Consistent functional abnormalities in patients with postpartum depression.

Postpartum depression (PPD) is a common public health concern. A wide range of functional abnormalities in various brain regions have been reported in fMRI studies on PPD, however, a consistent functional changing pattern is still lacking. Herein, we obtained functional Magnetic Resonance Imaging (fMRI) data from 52 patients with PPD and 24 healthy postpartum women (HPW). Functional indexes (low-frequency fluctuation, degree centrality, and regional homogeneity) were calculated and compared among these groups to explore the functional changing patterns of PPD. Then, correlation analyses were performed to investigate the relationship between changed functional indexes and clinical measurements in the PPD. Finally, support vector machine (SVM) was performed to test whether these abnormal features can be used to distinguish PPD from HPW. As a result, we identified significantly and consistently functional changing pattern characterizing by increased functional activity in the left inferior occipital gyrus and decreased functional activity right anterior cingulate cortex in the PPD as compared to HPW. These functional values in the right anterior cingulate cortex were significantly correlated with depression symptoms in the PPD, and can be used as features to distinguish PPD from HPW. In conclusion, our results suggested that the right anterior cingulate cortex could be served as a functional neuro-imaging biomarker for PPD, which might be used as a potential target for neuro-modulation.

Effects of freeze-thaw dynamics and microplastics on the distribution of antibiotic resistance genes in soil aggregates.

This is the first study investigating the effects of freeze-thaw (FT) and microplastics (MPs) on the distribution of antibiotic resistance genes (ARGs) in soil aggregates (i.e., soil basic constituent and functional unit) via microcosm experiments. The results showed that FT significantly increased the total relative abundance of target ARGs in different aggregates due to the increase in intI1 and ARG host bacteria. However, polyethylene MPs (PE-MPs) hindered the increase in ARG abundance caused by FT. The host bacteria carrying ARGs and intI1 varied with aggregate size, and the highest number of hosts was observed in micro-aggregates (<0.25 mm). FT and MPs altered host bacteria abundance by affecting aggregate physicochemical properties and bacterial community and enhanced multiple antibiotic resistance via vertical gene transfer. Although the dominant factors affecting ARGs varied with aggregate size, intI1 was a co-dominant factor in various-sized aggregates. Furthermore, other than ARGs, FT, PE-MPs, and their integration promoted the proliferation of human pathogenic bacteria in aggregates. These findings suggested that FT and its integration with MPs significantly affected ARG distribution in soil aggregates. They amplified antibiotic resistance environmental risks, contributing to a profound understanding of soil antibiotic resistance in the boreal region.