Rigorous benchmarking of T-cell receptor repertoire profiling methods for cancer RNA sequencing.

The ability to identify and track T-cell receptor (TCR) sequences from patient samples is becoming central to the field of cancer research and immunotherapy. Tracking genetically engineered T cells expressing TCRs that target specific tumor antigens is important to determine the persistence of these cells and quantify tumor responses. The available high-throughput method to profile TCR repertoires is generally referred to as TCR sequencing (TCR-Seq). However, the available TCR-Seq data are limited compared with RNA sequencing (RNA-Seq). In this paper, we have benchmarked the ability of RNA-Seq-based methods to profile TCR repertoires by examining 19 bulk RNA-Seq samples across 4 cancer cohorts including both T-cell-rich and T-cell-poor tissue types. We have performed a comprehensive evaluation of the existing RNA-Seq-based repertoire profiling methods using targeted TCR-Seq as the gold standard. We also highlighted scenarios under which the RNA-Seq approach is suitable and can provide comparable accuracy to the TCR-Seq approach. Our results show that RNA-Seq-based methods are able to effectively capture the clonotypes and estimate the diversity of TCR repertoires, as well as provide relative frequencies of clonotypes in T-cell-rich tissues and low-diversity repertoires. However, RNA-Seq-based TCR profiling methods have limited power in T-cell-poor tissues, especially in highly diverse repertoires of T-cell-poor tissues. The results of our benchmarking provide an additional appealing argument to incorporate RNA-Seq into the immune repertoire screening of cancer patients as it offers broader knowledge into the transcriptomic changes that exceed the limited information provided by TCR-Seq.

[Identification and functional analysis of jasmonic acid signaling repressor McJAZ8 gene in Mentha canadensis].

Mentha canadensis, as a plant with medicinal and culinary uses, holds significant economic value. Jasmonic acid signaling repressor JAZ protein has a crucial role in regulating plant response to adversity stresses. The M. canadensis McJAZ8 gene is cloned and analyzed for protein characterization, protein interactions, and expression patterns, so as to provide genetic resources for molecular breeding of M. canadensis for stress tolerance. This experiment will analyze the protein structural characteristics, subcellular localization, protein interactions, and gene expression of McJAZ8 using bioinformatics, yeast two-hybrid(Y2H), transient expression in tobacco leaves, qRT-PCR, and other technologies. The results show that:(1)The full length of the McJAZ8 gene is 543 bp, encoding 180 amino acids. The McJAZ8 protein contains conserved TIFY and Jas domains and exhibits high homology with Arabidopsis thaliana AtJAZ1 and AtJAZ2.(2)The McJAZ8 protein is localized in the nucleus and cytoplasm.(3)The Y2H results show that McJAZ8 interacts with itself or McJAZ1/3/4/5 proteins to form homologous or heterologous dimers.(4)McJAZ8 is expressed in different tissue, with the highest expression level in young leaves. In terms of leaf sequence, McJAZ8 shows the highest expression level in the fourth leaf and the lowest expression level in the second leaf.(5) In leaves and roots, the expression of McJAZ8 is upregulated to varying degrees under methyl jasmonate(MeJA), drought, and NaCl treatments. The expression of McJAZ8 shows an initial upregulation followed by a downregulation pattern under CdCl_2 treatment. In leaves, the expression of McJAZ8 tends to gradually decrease under CuCl_2 treatment, while in roots, it initially decreases and then increases before decreasing again. In both leaves and roots, the expression of McJAZ8 is downregulated to varying degrees under AlCl_(3 )treatment. This study has enriched the research on jasmonic acid signaling repressor JAZ genes in M. canadensis and provided genetic resources for the molecular breeding of M. canadensis.

[Cloning and expression pattern analysis of abscisic acid receptor gene McPYL4 in Mentha canadensis].

Mentha canadensis is a traditional Chinese herb with great medicinal and economic value. Abscisic acid(ABA) receptor PYLs have important roles in plant growth and development and response to adversity. The M. canadensis McPYL4 gene was cloned, and its protein characteristics, gene expression, and protein interactions were analyzed, so as to provide genetic resources for genetic improvement and molecular design breeding for M. canadensis resistance. Therefore, the protein characteristics, subcellular localization, gene expression pattern, and protein interactions of McPYL4 were analyzed by bioinformatics analysis, transient expression of tobacco leaves, RT-qPCR, and yeast two-hybrid(Y2H) techniques. The results showed that the McPYL4 gene was 621 bp in length, encoding 206 amino acids, and its protein had the conserved structural domain of SRPBCC and was highly homologous with Salvia miltiorrhiza SmPYL4. McPYL4 protein was localized to the cell membrane and nucleus. The McPYL4 gene was expressed in all tissue of M. canadensis, with the highest expression in roots, followed by leaves, and it showed a pattern of up-regulation followed by down-regulation in leaves 1-8. In both leaves and roots, the McPYL4 gene responded to the exogenous hormones ABA, MeJA, and the treatments of drought, AlCl_3, NaCl, CdCl_2, and CuCl_2. Moreover, McPYL4 was up-regulated for expression in both leaves and roots under the MeJA treatment, as well as in leaves treated with AlCl_3 stress for 1 h, whereas McPYL4 showed a tendency to be down-regulated in both leaves and roots under other treatments. Protein interactions showed that McPYL4 interacted with AtABI proteins in an ABA-independent manner. This study demonstrated that McPYL4 responded to ABA, JA, and several abiotic stress treatments, and McPYL4 was involved in ABA signaling in M. canadensis and thus in the regulation of leaf development and various abiotic stresses in M. canadensis.

Line-Features-Based Pose Estimation Method for the Disc Cutter Holder of Shield Machine.

To achieve automatic disc cutter replacement of shield machines, measuring the accurate pose of the disc cutter holder by machine vision is crucial. However, under polluted and restricted illumination conditions, achieving pose estimation by vision is a great challenge. This paper proposes a line-features-based pose estimation method for the disc cutter holder of the shield machine by using a monocular camera. For the blurring effect of rounded corners on the image edge, a rounded edge model is established to obtain edge points that better match the 3D model of the workpiece. To obtain the edge search box corresponding to each edge, a contour separation method based on an adaptive threshold region growing method is proposed. By preprocesses on the edge points of each edge, the efficiency and the accuracy of RANSAC linear fitting are improved. The experimental result shows that the proposed pose estimation method is highly reliable and can meet the measurement accuracy requirements in practical engineering applications.

Iodine-Modified Ag NPs for Highly Sensitive SERS Detection of Deltamethrin Residues on Surfaces.

It is essential to estimate the indoor pesticides/insecticides exposure risk since reports show that 80% of human exposure to pesticides occurs indoors. As one of the three major contamination sources, surface collected pesticides contributed significantly to this risk. Here, a highly sensitive liquid freestanding membrane (FSM) SERS method based on iodide modified silver nanoparticles (Ag NPs) was developed for quantitative detection of insecticide deltamethrin (DM) residues in solution phase samples and on surfaces with good accuracy and high sensitivity. The DM SERS spectrum from 500 to 2500 cm-1 resembled the normal Raman counterpart of solid DM. Similar bands at 563, 1000, 1165, 1207, 1735, and 2253 cm-1 were observed as in the literature. For the quantitative analysis, the strongest peak at 1000 cm-1 that was assigned to the stretching mode of the benzene ring and the deformation mode of C-C was selected. The peak intensity at 1000 cm-1 and the concentration of DM showed excellent linearity from 39 to 5000 ppb with a regression equation I = 649.428 + 1.327 C (correlation coefficient R2 = 0.991). The limit of detection (LOD) of the DM was found to be as low as 11 ppb. Statistical comparison between the proposed and the HPLC methods for the analysis of insecticide deltamethrin (DM) residues in solution phase samples showed no significant difference. DM residue analysis on the surface was mimicked by dropping DM pesticide on the glass surface. It is found that DM exhibited high residue levels up to one week after exposure. This proposed SERS method could find application in the household pesticide residues analysis.

Targeting TGF-ß signal transduction for fibrosis and cancer therapy.

Transforming growth factor ß (TGF-ß) has long been identified with its intensive involvement in early embryonic development and organogenesis, immune supervision, tissue repair, and adult homeostasis. The role of TGF-ß in fibrosis and cancer is complex and sometimes even contradictory, exhibiting either inhibitory or promoting effects depending on the stage of the disease. Under pathological conditions, overexpressed TGF-ß causes epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) deposition, cancer-associated fibroblast (CAF) formation, which leads to fibrotic disease, and cancer. Given the critical role of TGF-ß and its downstream molecules in the progression of fibrosis and cancers, therapeutics targeting TGF-ß signaling appears to be a promising strategy. However, due to potential systemic cytotoxicity, the development of TGF-ß therapeutics has lagged. In this review, we summarized the biological process of TGF-ß, with its dual role in fibrosis and tumorigenesis, and the clinical application of TGF-ß-targeting therapies.

Ameliorating SERS Sensitivity for Pesticide Malathion Detection with Synergistic Boosting Effect by Hydrogen Cations and Chloride Anions.

Although SERS has been widely recognized as one of the highly sensitive analytical methods that can be deployed in the field with high sensitivity and short analysis time, reports regarding the fast determination of malathion at low concentrations are still scarce. Here, in this work, the solution pH and various halogen co-adsorbates were explored to promote the SERS signal of malathion using the citrate-reduced Ag NPs. It was found that chloride anions were the most efficient signal booster among the three halogen ions screened. Further examination of the SERS profile of the malathion in the presence of different halogen species found that the stretching mode of the P-S bond shifted to a lower frequency with Cl-, which may imply closer (and stronger) binding of malathion to the Ag NPs. This concurs with literature reports that halogen ions could facilitate the adsorption of a certain analyte onto the SERS substrate. In addition, hydrogen ions showed a synergistic effect on SERS signal enhancement when combined with chloride anions. At optimum conditions, the malathion could be detected with a limit of detection (LOD) of 3 ppb. Malathion-spiked cherry tomatoes and oranges were analyzed, and the recovery rates were found to be within 85-100%.

Pose Determination of the Disc Cutter Holder of Shield Machine Based on Monocular Vision.

The visual measurement system plays a vital role in the disc cutter changing robot of the shield machine, and its accuracy directly determines the success rate of the disc cutter grasping. However, the actual industrial environment with strong noise brings a great challenge to the pose measurement methods. The existing methods are difficult to meet the required accuracy of pose measurement based on machine vision under the disc cutter changing conditions. To solve this problem, we propose a monocular visual pose measurement method consisting of the high precision optimal solution to the PnP problem (OPnP) method and the highly robust distance matching (DM) method. First, the OPnP method is used to calculate the rough pose of the shield machine's cutter holder, and then the DM method is used to measure its pose accurately. Simulation results show that the proposed monocular measurement method has better accuracy and robustness than the several mainstream PnP methods. The experimental results also show that the maximum error of the proposed method is 0.28° in the direction of rotation and 0.32 mm in the direction of translation, which can meet the measurement accuracy requirement of the vision system of the disc cutter changing robot in practical engineering application.

P53 suppresses the progression of hepatocellular carcinoma via miR-15a by decreasing OGT expression and EZH2 stabilization.

Existing literature has highlighted the tumour suppressive capacity of microRNA-15a (miR-15a); however, its role in hepatocellular carcinoma (HCC) remains relatively unknown. This study aimed to investigate the role of miR-15a in HCC and the associated underlying mechanism. Initially, RT-qPCR was performed to detect the expression of miR-15a in HCC tissues and cells. Bioinformatics analysis, Pearson correlation coefficient, dual-luciferase reporter assay, and molecular approaches were all conducted to ascertain the interaction between miR-15a and O-linked N-acetylglucosamine (GlcNAc) transferase (OGT). PUGNAc treatment and cycloheximide (CHX) assay were performed to evaluate O-GlcNAc and the stabilization of the enhancer of zeste homolog 2 (EZH2). Finally, gain- and loss-of-function studies were employed to elucidate the role of P53 and the miR-15a/OGT/EZH2 axis in the progression of HCC, followed by in vivo experiments based on tumour-bearing nude mice. Our results demonstrated that the miR-15a expression was decreased in the HCC tissues and cells. P53 upregulated miR-15a expression, which inhibited the proliferation, migration and invasion of HCC cells, while inducing apoptosis and triggering a G0/G1 cell cycle phase arrest. OGT stabilized EZH2 via catalysing O-GlcNAc, which reversed the effect of P53 and miR-15a. The results of our in vivo study provided evidence demonstrating that P53 could suppress the development of HCC via the miR-15a/OGT/EZH2 axis. P53 was found to inhibit the OGT expression by promoting the expression of miR-15a, which destabilized EZH2 and suppressed the development of HCC. The key findings of our study highlight a promising novel therapeutic strategy for the treatment of HCC.

Short communication: The lag response of daily milk yield to heat stress in dairy cows.

Previous studies suggest that there exists a lag relationship between daily milk yield and heat stress. The values of heat stress indicators (e.g., temperature-humidity index and ambient temperature) before test day have a simple correlation with daily milk yield on test day. However, the simple correlation might not be the best description because daily milk yield and heat stress indicators have a nature of time series in common, and their correlations are cross correlations that could be affected by autocorrelations. We hope to give a more reliable estimation on the lag relationship of daily milk yield via excluding autocorrelations with transfer function modeling. In this study, we found a lag relationship between daily milk yield and heat stress indicators based on transfer function modeling. Heat stress indicators included ambient temperature and temperature-humidity index. The daily milk yield data from 123 cows were obtained during a consecutive 63-d period (July 10-September 10, 2016). The mean daily milk yield (MY) and the maximum daily ambient temperature (TA_max) satisfied the stationary hypothesis, and the cross correlation between them was calculated. Before excluding autocorrelation, MY at 0 to 4 d after test day had significant cross correlations with TA_max on test day. After excluding the influence of autocorrelations, MY at 1 to 3 d after the test day had significant cross correlations with TA_max on test day. This result suggested that MY would respond to TA_max 1 d after the test day. In addition, the strength of cross correlations between MY and TA_max decreased from 1 to 3 d in sequence, implying a declining lag response of MY that would last for 3 d. The transfer function model for MY and TA_max is written as: MYt = 16.90 + 0.74MYt- 1 - 0.25TA_maxt- 1 + Nt, where Nt is white noise. This model can be used to track and predict the dynamic response of MY to TA_max.

Predicting rectal temperature and respiration rate responses in lactating dairy cows exposed to heat stress.

Milk production and time effects are considered related to heat stress but they have not yet been combined in predictive models. In two parts, this study aimed to develop new models to predict heat stress (rectal temperature and respiration rate) of lactating dairy cows by inputting predictors, including ambient temperature (Ta), relative humidity (RH), wind speed (WS), milk yield (MY), and time blocks. In the first part of the study, we built the quantitative foundation for the second part, including the regression relation between respiration rate and rectal temperature (to convert predicted respiration rate to predicted body temperature), as well as between rectal temperature and respiration rate when heat stress was triggered (to recognize whether herds were under stress). In the second part, we built models that combined the abovementioned predictors to predict respiration rate. In part I, data were obtained from 45 high-producing Holstein cows within a Ta range of 9.5 to 30.8°C. We found a very strong correlation between mean respiration rate (MRR) and mean rectal temperature (MRT), where MRT = 0.021 × MRR + 37.6 (R2 = 0.925), suggesting that for each 4.8 breaths per minute (bpm) increase of MRR, MRT would be expected to increase by 0.1°C. Rectal temperature was determined to be 38.6°C when heat stress was triggered, which corresponded to a respiration rate of 48 bpm. In part II, data were obtained in 3 stalls within a Ta range of 6.9 to 33.3°C over 3 time blocks, all of which were the 90 min preceding milking (0630-0800, 1230-1400, and 1830-2000 h). We found a nonlinear response of MRR to Ta, which could be linearized by the quadratic term of Ta. The response of MRR was the highest in the 0630-0800 h block, followed by 1230-1400 h, and finally 1830-2000 h. We proposed a model combining 3 time blocks (R2 = 0.836): MRR in 0630-0800 h was determined to 56.28 + (-3.40 + 0.11 × Ta + 0.02 × RH) × Ta - 0.21 × RH - 2.82 × WS + 0.62 × MY; MRR in 1230-1400 h and 1830-2000 h were 4.6 and 10.3 bpm lower than that in 0630-0800 h, respectively (reducing the intercept of the expression in 0630-0800 h). Compared with temperature-humidity index equations, the proposed model performed better at suppressing prediction error, and had better sensitivity and accuracy in recognizing whether heat stress was triggered.

Study on FcγRn Electrochemical Receptor Sensor and Its Kinetics.

Neonatal γ-immunoglobulin (IgG) Fc receptor (FcγRn) is a receptor that transports IgG across the intestinal mucosa, placenta, and mammary gland, ensuring the balance of IgG and albumin in the body. These functions of FcγRn depend on the intracellular signal transduction and activation caused by the combination of its extracellular domain and IgG Fc domain. Nevertheless, there are still no kinetic studies on this interaction. Consequently, in the present study, we successfully constructed the human FcγRn (hFcγRn) electrochemical receptor sensor. The signal amplification system formed by chitosan nanogold-hFcγRn protein and horseradish peroxidase was used to simulate the cell signal amplification system in vivo, and the kinetic effects between seven IgG and hFcγRn receptors from different species were quantitatively measured. The results showed that the interaction of these seven IgGs with hFcγRn was similar to the catalytic kinetics of enzyme and substrate, and there was a ligand-receptor saturation effect. The order of the interconnect allosteric constants (Ka), which is similar to the Michaelis constant (Km), was human IgG < bovine IgG < horse IgG < rabbit IgG < sheep IgG < donkey IgG < quail IgY. The results showed that hFcγRn had the strongest ability to transport human IgG, which was consistent with the evolution of the system. Therefore, our hFcγRn electrochemical receptor sensor can be used to measure and evaluate the interconnected allosteric network. It is also an essential parameter of the interaction between hFcγRn and different IgGs and, thus, provides a new detection and evaluation method for immunoemulsion, therapeutic monoclonal antibody therapy, heteroantibody treatment, and half-life research.

[Parents' antibiotic use for children in Ningbo: knowledge, behaviors and influencing factors].

OBJECTIVE: To survey the knowledge and behaviors of antibiotic use for children among parents in Ningbo and to explore the influencing factors. METHODS: One kindergarten and one primary school were randomly selected in Yinzhou and Beilun District of Ningbo using stratified random cluster sampling method, respectively. A survey on the knowledge and behaviors of antibiotics use for children was conducted with a self-designed questionnaire among parents of children aged 2 to 14 years in the sampled kindergarten and school. RESULTS: The scores of antibiotic use knowledge were 0-4 in 36.6%(1028/2806) of parents. In the past month, 56.6%(556/983) of parents self-medicated their children, including 20.3%(113/556) medicated with antibiotics. In the past year, 48.5%(1361/2806) of parents stored antibiotics for children at home. Multivariate logistic regression analysis showed that mother, and parents with city residence, higher education level, higher household income, medical background, male children and younger children had higher antibiotic use knowledge scores(P<0.05 or P<0.01); parents with city residence, higher education level and medical background were more likely to store antibiotics at home (all P<0.01); parents with city residence and those store antibiotics at home were more likely to self-medicate their children with antibiotics (P<0.05 or P<0.01). CONCLUSIONS: sPoor knowledge and massive antibiotic missuse for children among parents are of great concern in Ningbo. Tailored health education programs are needed to improve the knowledge and behaviors of rational antibiotic use among parents and reduce storage of antibiotics at home.

Clones of FeSOD, MDHAR, DHAR Genes from White Clover and Gene Expression Analysis of ROS-Scavenging Enzymes during Abiotic Stress and Hormone Treatments.

Increased transcriptional levels of genes encoding antioxidant enzymes play important protective roles in coping with excessive accumulation of reactive oxygen species (ROS) in plants exposed to various abiotic stresses. To fully elucidate different evolutions and functions of ROS-scavenging enzymatic genes, we isolated iron superoxide dismutase (FeSOD), dehydroascorbate reductase (DHAR) and monodehydroascorbate reductase (MDHAR) from white clover for the first time and subsequently tested dynamic expression profiles of these genes together with previously identified other antioxidant enzyme genes including copper zinc superoxide dismutase (Cu/ZnSOD), manganese superoxide dismutase (MnSOD), glutathione reductase (GR), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) in response to cold, drought, salinity, cadmium stress and exogenous abscisic acid (ABA) or spermidine (Spd) treatment. The cloned fragments of FeSOD, DHAR and MDHAR genes were 630, 471 and 669 bp nucleotide sequences encoding 210, 157 and 223 amino acids, respectively. Phylogenetic analysis indicated that both amino acid and nucleotide sequences of these three genes are highly conservative. In addition, the analysis of genes expression showed the transcription of GR, POD, MDHAR, DHAR and Cu/ZnSOD were rapidly activated with relatively high abundance during cold stress. Differently, CAT, APX, FeSOD, Cu/ZnSOD and MnSOD exhibited more abundant transcripts compared to others under drought stress. Under salt stress, CAT was induced preferentially (3-12 h) compared to GR which was induced later (12-72 h). Cadmium stress mainly up-regulated Cu/ZnSOD, DHAR and MDHAR. Interestingly, most of genes expression induced by ABA or Spd happened prior to various abiotic stresses. The particular expression patterns and different response time of these genes indicated that white clover differentially activates genes encoding antioxidant enzymes to mitigate the damage of ROS during various environmental stresses.

Evaluating ARG-estimation methods in the context of estimating population-mean polygenic score histories.

Scalable methods for estimating marginal coalescent trees across the genome present new opportunities for studying evolution and have generated considerable excitement, with new methods extending scalability to thousands of samples. Benchmarking of the available methods has revealed general tradeoffs between accuracy and scalability, but performance in downstream applications has not always been easily predictable from general performance measures, suggesting that specific features of the ARG may be important for specific downstream applications of estimated ARGs. To exemplify this point, we benchmark ARG estimation methods with respect to a specific set of methods for estimating the historical time course of a population-mean polygenic score (PGS) using the marginal coalescent trees encoded by the ancestral recombination graph (ARG). Here we examine the performance in simulation of six ARG estimation methods: ARGweaver, RENT+, Relate, tsinfer+tsdate, ARG-Needle/ASMC-clust , and SINGER , using their estimated coalescent trees and examining bias, mean squared error (MSE), confidence interval coverage, and Type I and II error rates of the downstream methods. Although it does not scale to the sample sizes attainable by other new methods, SINGER produced the most accurate estimated PGS histories in many instances, even when Relate, tsinfer+tsdate , and ARG-Needle/ASMC-clust used samples ten times as large as those used by SINGER. In general, the best choice of method depends on the number of samples available and the historical time period of interest. In particular, the unprecedented sample sizes allowed by Relate, tsinfer+tsdate , and ARG-Needle/ASMC-clust are of greatest importance when the recent past is of interest-further back in time, most of the tree has coalesced, and differences in contemporary sample size are less salient.

Evaluating the mechanism of soybean meal protein for boosting the laccase-catalyzed of thymol onto lignosulfonate via restraining non-specific adsorption.

The control of laccase-catalyzed efficiency often relies on the utilization of modifying enzyme molecules and shielding agents. However, their elevated costs or carcinogenicity led to the inability for large-scale application. To address this concern, we found that a low-cost protein from soybean meal can reduce lignin's ineffective adsorption onto enzymes for improving the efficiency of thymol grafting to lignosulfonate. The results demonstrated that by adding 0.5 mg/mL of additional soybean meal protein, the thymol reaction ratio of the modified lignosulfonate (L-0.5 S) significantly boosted from 18.1 % to 35.0 %, with the minimal inhibitory concentrations of the L-0.5 S against Aspergillus niger dramatically improved from 12.5 mg/mL to 3.1 mg/mL. Multiple characterization methods were employed to better understand the benefit of the modification under the addition of the soybean meal protein. The CO and R1-O group content increased from 20.5 % to 37.8 % and from 65.1 % to 75.5 %, respectively. The proposed potential reaction mechanism was further substantiated by the physicochemical properties. The incorporation of soybean meal effectively mitigated the non-specific adsorption of lignosulfonate, resulting in a reduction of the surface area of lignin from 235.0 to 139.2 m2/g. The utilization of soybean meal as a cost-effective and efficient shielding agent significantly enhanced the efficiency of subsequent enzyme catalysis. Consequently, the application of soybean meal in commercial enzyme catalysis holds considerable appeal and amplifies the relevance of this study in preservative industries.

Clinical and cardiac characteristics of primary bilateral macronodular adrenal hyperplasia.

Background: Cardiovascular disease is the leading cause of death in Cushingzs syndrome (CS). Primary bilateral macro-nodular adrenal hyperplasia (PBMAH), is a rare cause of CS that is clinically distinct from the other common types of CS, but cardiac characteristics have been poorly studied. Methods: The clinical data, steroid hormones and echocardiographic variables of 17 patients with PBMAH were collected. Twenty-one CS patients with cortisol-producing adenoma (CPA) were collected as controls. The similarities and differences of clinical and cardiac features between the two groups were compared.

Spermidine or spermine pretreatment regulates organic metabolites and ions homeostasis in favor of white clover seed germination against salt toxicity.

White clover is widely cultivated as a leguminous forage or ground cover plant worldwide. However, soil salinization decreases its yield and quality. Aims of the present experiment were to elucidate the impact of seed pretreatment with spermidine (Spd) or spermine (Spm) on amylolysis, Na+/K+ accumulation, and metabolic homeostasis during germination. Seed was soaked in distilled water (control), Spd or Spm solution and then germinated under optimal or salt stress conditions for 7 days. Results showed that germination vigor, germination percentage, or seed vigour index of seeds pretreatment with Spd increased by 7%, 11%, or 70% when compared with water-pretreated seeds under salt stress, respectively. Germination percentage or seed vigour index of seeds pretreatment with Spm increased by 17% or 78% than water-pretreated seeds under saline condition, respectively. In response to salt stress, accelerated amylolysis via activation of ß-amylase activity was induced by Spd or Spm pretreatment. Spd or Spm pretreatment also significantly enhanced accumulation of diverse amino acids, organic acids, sugars, and other metabolites (putrescine, myo-inositol, sorbitol, daidzein etc.) associated with enhanced osmotic adjustment, antioxidant capacity, and energy supply during germination under salt stress. In addition, Spd or Spm pretreatment not only significantly reduced salt-induced K+ loss and overaccumulation of Na+, but also improved the ratio of K+ to Na+, contributing to Na+ and K+ balance in seedlings. In response to salt stress, seeds pretreatment with Spd or Spm up-regulated transcription level of NHX2 related to enhancement in compartmentation of Na+ from cytoplasm to vacuole, thus reducing Na+ toxicity in cytoplasm. Spm priming also uniquely up-regulated transcription levels of SKOR, HKT1, and HAL2 associated with K+ and Na + homeostasis and decline in cytotoxicity under salt stress.

Five new flavonoids and their pharmacological activities from Iris tenuifolia Pall.

Five new components including two new isoflavones, 5, 7, 2', 3'-tetrahydroxy-6-methoxyisoflavone (1), 5, 7, 2', 3'-tetrahydroxy-8-methoxyisoflavone (2), one flavonol 3, 5, 3', 4'-tetrahydroxy-7, 2'-dimethoxyflavonol (3), one flavanone (2S)-5, 7, 3'-trihydroxy-2'-methoxyflavanone (4), and one flavanonol (2R, 3R)-3, 5, 3', 4'-tetrahydroxy-7, 2'-dimethoxyflavanonol (5), along with nine known flavonoids (6-14) were isolated from under ground parts of Iris tenuifolia Pall. Their structures were elucidated by NMR and HRESIMS data and by comparison of CD spectra with compounds having similar structure. The separated compounds were evaluated for in vitro antioxidant activities by DPPH and ABTS. The α-glucosidase inhibitory activity of the compounds were evaluated with the pNPG method, the results indicated flavonoids were potential inhibitors of α-glucosidase. Moreover, in vitro anti-oxidative assay using flow cytometry indicated that compounds 1-5 showed strong oxidation resistance ability on C8D1A cells without affecting the cell viability.

A bimodal feature fusion convolutional neural network for detecting obstructive sleep apnea/hypopnea from nasal airflow and oximetry signals.

The most prevalent sleep-disordered breathing condition is Obstructive Sleep Apnea (OSA), which has been linked to various health consequences, including cardiovascular disease (CVD) and even sudden death. Therefore, early detection of OSA can effectively help patients prevent the diseases induced by it. However, many existing methods have low accuracy in detecting hypopnea events or even ignore them altogether. According to the guidelines provided by the American Academy of Sleep Medicine (AASM), two modal signals, namely nasal pressure airflow and pulse oxygen saturation (SpO2), offer significant advantages in detecting OSA, particularly hypopnea events. Inspired by this notion, we propose a bimodal feature fusion CNN model that primarily comprises of a dual-branch CNN module and a feature fusion module for the classification of 10-second-long segments of nasal pressure airflow and SpO2. Additionally, an Efficient Channel Attention mechanism (ECA) is incorporated into the second module to adaptively weight feature map of each channel for improving classification accuracy. Furthermore, we design an OSA Severity Assessment Framework (OSAF) to aid physicians in effectively diagnosing OSA severity. The performance of both the bimodal feature fusion CNN model and OSAF is demonstrated to be excellent through per-segment and per-patient experimental results, based on the evaluation of our method using two real-world datasets consisting of polysomnography (PSG) recordings from 450 subjects.