Inactivation of a Wheat Ribosomal Silencing Factor Gene TaRsfS Confers Resistance to Both Powdery Mildew and Stripe Rust.

Powdery mildew and stripe rust are major diseases on wheat worldwide that cause significant reductions in wheat production. The ribosomal silencing factor (RsfS) has been proven to regulate protein biosynthesis by inhibiting the translation process in bacterial response to stress. However, the role of RsfS in plant resistance to biotic stresses remains unclear. In this study, the RsfS homolog, TaRsfS was isolated from wheat. Overexpression of TaRsfS (TaRsfS-OE) reduces wheat resistance to powdery mildew and stripe rust and TaRsfS knockout (TaRsfS-KO) increases wheat resistance to both diseases without affecting key agronomic traits. The interaction protein of TaRsfS, 12-oxo-phytodienoic acid reductase 1 (TaOPR1), a key enzyme in the biosynthesis of jasmonic acid (JA), was screened and identified. Knocking-down and overexpression of TaOPR1 indicated that TaOPR1 positively regulates wheat resistance to powdery mildew and stripe rust. TaRsfS may regulate TaOPR1 at upstream, bind to the enzyme activity pocket of TaOPR1 and affect TaOPR1 enzyme activity, resulting in a reduced JA biosynthesis and wheat susceptible to powdery mildew and stripe rust. Collectively, TaRsfS is a susceptibility gene and negatively regulates wheat resistance to powdery mildew and stripe rust, and it has good potential for improving wheat resistance by genetic modifications.

Diosmin ameliorates inflammation, apoptosis and activates PI3K/AKT pathway in Alzheimer's disease rats.

Alzheimer's disease (AD), a prevalent cognitive disorder among the elderly, is frequently linked to the abnormal accumulation of myloid-ß (Aß), which is mainly as a result of neuronal death and inflammation. Diosmin, a flavonoid, is considered a potential drug for the treatment of AD. Our study aimed to uncover the molecular mechanism of diosmin in AD therapy. Here, rats were randomly divided into three groups: control, Aß25-35, and Aß25-35 + diosmin groups. AD model rats were induced by Aß25-35 intraventricular injection, meanwhile 50 mg/kg diosmin was orally administered for 6-week intervention. Morris water maze test assessed learning and memory abilities. Hippocampal neuronal damage was determined by HE, Nissl, and TUNEL staining. These assays indicate that diosmin improves cognitive dysfunction and reduces hippocampal neuronal loss and apoptosis. Western blot showed that diosmin reduced Bax (1.21 ± 0.12) and cleaved caspase-3 (1.27 ± 0.12) expression, and increased Bcl-2 (0.70 ± 0.06), p-PI3K (0.71 ± 0.08), and p-AKT (0.96 ± 0.10) in the hippocampus. ELISA indicated diosmin reduces IL-1ß, IL-6, and TNF-α levels, suggesting anti-inflammation effect. These results suggest that diosmin inhibits neuronal apoptosis and neuroinflammatory responses to improve cognitive dysfunction in AD rats, possibly related to upregulation of the PI3K/AKT pathway, providing a scientific basis for its use in AD treatment.

A method of motion estimation of segmental ventricular wall with tracking of ultrasonic echocardiogram.

BACKGROUND: Ultrasonic echocardiography is commonly used for monitoring myocardial dysfunction. However, it has limitations such as poor quality of echocardiography images and subjective judgment of doctors. METHODS: In this paper, a calculation model based on optical flow tracking of echocardiogram is proposed for the quantitative estimation motion of the segmental wall. To improve the accuracy of optical flow estimation, a method based on confidence-optimized multiresolution(COM) optical flow model is proposed to reduce the estimation errors caused by the large amplitude of myocardial motion and the presence of "shadows" and other image quality problems. In addition, motion vector decomposition and dynamic tracking of the ventricular region of interest are used to extract information regarding the myocardial segmental motion. The proposed method was validated using simulation images and 50 clinical cases (25 patients and 25 healthy volunteers) for myocardial motion analysis. RESULTS: The results demonstrated that the proposed method could track the motion information of myocardial segments well and reduce the estimation errors of optical flow caused due to the use of low-quality echocardiogram images. CONCLUSIONS: The proposed method improves the accuracy of motion estimation for the cardiac ventricular wall.

DNA2 mutation causing multisystemic disorder with impaired mitochondrial DNA maintenance.

PURPOSE: To describe a novel DNA2 variant contributing to defects in mtDNA maintenance and mtDNA depletion syndrome (MDS), and the clinical and histological findings associated with this variation. METHODS: Herein, we describe the case of a patient who presented with hearing loss and myopathy, given the family history of similar findings in the father, was evaluated by sequencing of the deafness gene panel, mitochondrial genome, and the exome. Furthermore, tissue staining, mtDNA copy number detection, mtDNA sequencing, and long-range polymerase chain reaction tests were also conducted on the muscle biopsy specimen. In vitro experiments, including analyses of the mtDNA copy number; levels of ATP, ATPase, and reactive oxygen species (ROS); and the membrane potential, were performed. RESULTS: The DNA2 heterozygous truncating variant c. 2368C > T (p.Q790X) was identified and verified as the cause of an mtDNA copy number decrement in both functional experiments and muscle tissue analyses. These changes were accompanied by reductions in ATP, ATPase, and ROS levels. CONCLUSION: The DNA2 variant was a likely cause of MDS in this patient. These findings expand the mutational spectrum of MDS and improve our understanding of the functions of DNA2 by revealing its novel role in mtDNA maintenance.

Molecular Mapping of a Recessive Powdery Mildew Resistance Gene in Wheat Cultivar Tian Xuan 45 Using Bulked Segregant Analysis with Polymorphic Single Nucleotide Polymorphism Relative Ratio Distribution.

Powdery mildew is a destructive foliar disease of wheat worldwide. Wheat cultivar Tian Xuan 45 exhibits resistance to the highly virulent isolate HY5. Genetic analysis of the F2 and F2:3 populations of a cultivar Ming Xian 169/Tian Xuan 45 cross revealed that the resistance to HY5 was controlled by a single recessive gene, temporarily designated as PmTx45. A Manhattan plot with the relative frequency distribution of single nucleotide polymorphisms (SNPs) was used to rapidly narrow down the possible chromosomal regions of the associated genes. This microarray-based bulked segregant analysis (BSA) largely improved traditional analytical methods. PmTx45 was located in chromosomal bin 4BL5-0.86-1.00 and was flanked by SNP marker AX-110673642 and intron length polymorphism (ILP) marker ILP-4B01G269900 with genetic distances of 3.0 and 2.6 cM, respectively. Molecular detection in a panel of wheat cultivars using the markers linked to PmTx45 showed that the presence of PmTx45 in commercial wheat cultivars was rare. Resistance spectrum and chromosomal position analyses indicated that PmTx45 may be a novel recessive gene with moderate powdery mildew resistance. This new microarray-based BSA method is feasible and effective and has the potential application for mapping genes in wheat in marker-assisted breeding.

Crocin ameliorates neuroinflammation and cognitive impairment in mice with Alzheimer's disease by activating PI3K/AKT pathway.

BACKGROUND: Crocin has a good prospect in the treatment of Alzheimer's disease (AD), but the mechanisms underlying its neuroprotective effects remain elusive. This study aimed to investigate the neuroprotective effects of Crocin and its underlying mechanisms in AD. METHODS: AD mice were set up by injecting Aß25-35 solution into the hippocampus. Then, the AD mice were injected intraperitoneally with 40 mg/kg/day of Crocin for 14 days. Following the completion of Crocin treatment, an open-field test, Y-maze test and Morris water maze test were conducted to evaluate the impact of Crocin on spatial learning and memory deficiency in mice. The effects of Crocin on hippocampal neuron injury, proinflammatory cytokine expressions (IL-1ß, IL-6, and TNF-α), and PI3K/AKT signaling-related protein expressions were measured using hematoxylin and eosin staining, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) experiments, respectively. RESULTS: Crocin attenuated Aß25-35-induced spatial learning and memory deficiency and hippocampal neuron injury. Furthermore, the Western blot and qRT-PCR results showed that Crocin effectively suppressed inflammation and activated the PI3K/AKT pathway in Aß25-35-induced mice. CONCLUSION: Crocin restrained neuroinflammation via the activation of the PI3K/AKT pathway, thereby ameliorating the cognitive dysfunction of AD mice.

Mechanically robust and electrically conductive nanofiber composites with enhanced interfacial interaction for strain sensing.

Electrically conductive fiberfibre/fabric composites (ECFCs) are competitive candidates for use in wearable electronics. Therefore, it is essential to develop mechanically robust ECFC strain sensors with sensing performance. In this study, MXene assembly and hot-pressing were combined to prepare strong yet breathable ECFCs for strain and temperature sensing. Hydrogen bonding between MXene and polyurethane (PU) and ultrasonication-induced interfacial sintering were responsible for MXene nanosheets assembly on the PU nanofibers. MXene decoration made PU nanofibers electrically conductive, resulting in a conductive network. Hot-pressing improved interface adhesion among the conductive nanofibers. Thus, the mechanical properties of the nanofiber composites, including tensile strength, toughness and fracture energy, were enhanced. The nanofiber composites exhibited surface stability and durability. When the nanofiber composites were used as strain sensors, they showed breathability with a linear resistance response ranging from 1 % to 100 % and cycling stability. In addition, they produced stable sensing signals over 1000 cycles when a notch was present. They could also monitor temperature variations with a negative temperature coefficient (-0.146 %/°C). This study provides an interfacial regulation method for the preparation of multi-functional nanofiber composites with potential applications in flexible and wearable electronics.

Unveiling the hidden risk: paternal smoking and alcohol exposure prior to conception as independent factors for allergic rhinitis in children.

Introduction: Limited knowledge exists regarding the impact of paternal smoking and alcohol exposure on the development of allergic rhinitis in offspring. Our study aimed to investigate the potential association between preconception paternal smoking and alcohol exposure and the likelihood of children allergic rhinitis. Methods: A retrospective case-control study of 556 prepubertal children aged 3-12 years was performed. The participants were 278 children with allergic rhinitis and 278 healthy controls matched for age and gender. Self-administered questionnaires were distributed and collected on-site, focusing on various factors related to the children's fathers, mothers, and the children themselves during the first year of life and the past 12 months, from March to October 2022. Results: Multivariate analysis demonstrated that paternal smoking, paternal alcohol consumption prior to conception, paternal allergic diseases, children with a family history of allergies, maternal allergic diseases and pregnancy complications were identified as independent risk factors for allergic rhinitis in their offspring. Moreover, after considering confounding factors, it was observed that paternal smoking exceeding 5 cigarettes per day in the year preceding pregnancy and exceeding 11 years significantly elevated the likelihood of allergic rhinitis in children (OR = 2.009 and 2.479, respectively). Furthermore, the consumption of alcohol by the father at intervals of less than one month in the year prior to pregnancy and a duration of alcohol consumption exceeding 11 years prior to pregnancy are both associated with a significantly increased risk of allergic rhinitis in children (OR = 2.005 and 3.149, respectively). Conclusions: Paternal smoking and alcohol consumption prior to conception contribute to an increased risk of allergic rhinitis in children, with the risk being dependent on the dosage and duration of exposure. Therefore, it is important to not only focus on personal and maternal environmental exposures when considering the occurrence risk of allergic rhinitis in children, but also to consider paternal detrimental exposures prior to conception.

Ginsenoside Rg2 alleviates neurovascular damage in 3xTg-AD mice with Alzheimer's disease through the MAPK-ERK pathway.

Alzheimer's disease (AD) is the most common form of dementia, and ginsenoside Rg2 (Rg2) is proven to inhibit AD's progression. This study investigates the potential benefits of Rg2 treatment on 3xTg-AD mice. Following 6 weeks of gavage treatment, Rg2-treated 3xTg-AD mice exhibited improved spatial recognition memory behaviors, regional cerebral blood flow, and histopathological injury of the hippocampus, which were observed through a Y-maze test, laser Doppler flowmetry, and hematoxylin-eosin staining. Additionally, Rg2 treatment caused a decrease in the levels of amyloid beta 25-35, TNF-α, IL-1ß, and IL-6, as measured by enzyme-linked immunosorbent assay, as well as a reduction in mRNA levels of IL-1ß and IL-6 in 3xTg-AD mouse brains using quantitative real-time PCR. In particular, NeuN and CD31 levels were inhibited and GFAP level was elevated in 3xTg-AD mice that were observed through immunofluorescence, and these levels were all antagonized by Rg2, suggesting the effects of Rg2 on neurovascular damage, astrocyte activation, and neuronal loss. Furthermore, Western blot and qRT-PCR assays showed that Rg2 blocked the expression of ICAM-1 and VCAM-1 in 3xTg-AD mice. By Western blot, the ratios of p-ERK/ERK and p-MAPK/MAPK in 3xTg-AD mice were upregulated by Rg2 treatment, suggesting the neuroprotective effects of Rg2 may be related to the MAPK-ERK pathway. In summary, this study demonstrated the potential of Rg2 to improve AD and provided a scientific basis for research on the biological mechanism of AD and the development of Rg2.

Curcumin alleviates Alzheimer's disease by inhibiting inflammatory response, oxidative stress and activating the AMPK pathway.

BACKGROUND: Alzheimer's disease (AD) is a common degenerative brain disorder with limited therapeutic options. Curcumin (Cur) exhibits neuroprotective function in many diseases. We aimed to explore the role and mechanism of Cur in AD. MATERIALS AND METHODS: Firstly, we established AD mice by injecting amyloid-ß1-42 (Aß1-42) solution into the hippocampus. Then, the AD mice received 150 mg/kg/d Cur for 10 consecutive days. The Morris water maze test was conducted to evaluate the cognitive function of the mice by hidden platform training and probe trials. To assess the spatial memory of the mice, spontaneous alternation behavior, the number of crossing the novel arm and the time spent in the novel arm during the Y-maze test was recorded. Hematoxylin and eosin (H&E) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNAL) assay were performed to assess the pathological damage and apoptosis of brain tissues. The number of damaged neurons was inspected by Nissl staining. Immunohistochemical staining was then performed to detect Aß1-42 deposition. The levels of tumor necrosis factor-α (TNF-a), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) in serum and hippocampus, the contents of super oxide dismutase (SOD) and malondialdehyde (MDA) in brain tissues were assessed by enzyme-linked immunosorbent assay (ELISA). Additionally, B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), RelA (p65) protein expressions and Adenosine 5'-monophosphate-activated protein kinase (AMPK) phosphorylation were tested using Western blot. RESULTS: Cur not only improved cognitive function and spatial memory, but also alleviated the pathological damage and apoptosis of brain tissues for AD mice. Meanwhile, upon Cur treatment, the number of damaged neurons in AD mice was decreased, the level of Aß1-42 in AD mice was significantly decreased. Furthermore, the AD mice treated with Cur exhibited lower TNF-a, IL-6, IL-1ß and MDA levels and a higher SOD content. Besides, Cur also downregulated p65 expression and upregulated AMPK phosphorylation. CONCLUSION: Cur may improve AD via suppressing the inflammatory response, oxidative stress and activating the AMPK pathway, suggesting that Cur may be a potential drug for AD.

Cnidium monnieri (L.) Cusson Flower as a Supplementary Food Promoting the Development and Reproduction of Ladybeetles Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae).

Predaceous ladybeetles are highly polyphagous predators that ingest supplementary food from flowering plants. Flowering plants widely grown in agroecosystems can sustain multiple natural enemies of agricultural pests, and the pollen and nectar resources from flowering plants may have a positive role in natural enemies. Cnidium monnieri (L.) Cusson, an annual herb with many flowers, blooms from May to July. C. monnieri can support several predatory natural enemies, and the addition of C. monnieri strips increases the density of Harmonia axyridis (Pallas) and improves the biological control of apple aphids in an apple orchard. H. axyridis is also the most important natural enemy in wheat aphid biocontrol and is attracted to healthy and aphid-infested C. monnieri plants. In addition, adult Propylaea japonica Thunberg survives significantly longer on C. monnieri flowers than on a water-only diet. In this study, a laboratory experiment was conducted to assess (i) the effect of nutritional supplements derived from C. monnieri flowers on the development and reproduction of H. axyridis under a wheat aphids-only diet; (ii) the effect of C. monnieri flowers on H. axyridis adult reproduction performance. We compared the larval durations, survival, weight, adult longevity, and reproduction of H. axyridis reared on wheat aphids-only and aphids plus C. monnieri flower diets. The results showed that H. axyridis larvae reared on aphids plus flowers had significantly greater weights and survival rates, shorter larval durations, and produced 1.62 times more eggs than those reared on wheat aphids-only diets. H. axyridis adults ingesting a C. monnieri flowers plus an aphid diet increased egg production 1.44 times compared to the aphids-only diet. Our study demonstrates that C. monnieri flowers as a supplementary food positively affect the survival, development, and reproduction performance of H. axyridis.

Autosomal dominant non-syndromic hearing loss caused by a novel mutation in MYO7A: A case report and review of the literature.

BACKGROUND: Variants in the MYO7A gene commonly result in Usher syndrome, and in rare cases lead to autosomal dominant non-syndromic deafness (DFNA11). Currently, only nine variants have been reported to be responsible for DFNA11 and their clinical phenotypes are not identical. Here we present a novel variant causing DFNA11 identified in a three-generation Chinese family. CASE SUMMARY: The proband was a 53-year-old Han male who presented with post-lingual bilateral symmetrical moderate sensorineural hearing loss. We learned from the patient's medical history collection that multiple family members also had similar hearing loss, generally occurring around the age of 40. Subsequent investigation by high-throughput sequencing identified a novel MYO7A variant. To provide evidence supporting that this variant is responsible for the hearing loss in the studied family, we performed Sanger sequencing on 11 family members and found that the variant co-segregated with the deafness phenotype. In addition, the clinical manifestation of the 11 affected family members was found to be late-onset bilateral slowly progressive hearing loss, inherited in this family in an autosomal dominant manner. None of the affected family members had visual impairment or vestibular symptoms; therefore, we believe that this novel MYO7A variant is responsible for the rare DFNA11 in this family. CONCLUSION: We report a novel variant leading to DFNA11 which further enriches the collection of MYO7A variants, and our review of the nine previous variants that have been identified to cause DFNA11 provides a reference for clinical genetic counseling.

Contribution of inter-trial phase coherence at theta, alpha, and beta frequencies in auditory change detection.

Introduction: Auditory change detection is a pre-attentive cortical auditory processing ability. Many neurological and psychological disorders can lead to defects in this process. Some studies have shown that phase synchronization may be related to auditory discrimination. However, the specific contributions of phase synchronization at different frequencies remain unclear. Methods: We analyzed the electroencephalogram (EEG) data of 29 healthy adults using an oddball paradigm consisting of a standard stimulus and five deviant stimuli with varying frequency modulation patterns, including midpoint frequency transitions and linear frequency modulation. We then compared the peak amplitude and latency of inter-trial phase coherence (ITC) at the theta(θ), alpha(α), and beta(ß) frequencies, as well as the N1 component, and their relationships with stimulus changes. At the same time, the characteristics of inter-trial phase coherence in response to the pure tone stimulation and chirp sound with a fine time-frequency structure were also assessed. Result: When the stimulus frequency did not change relative to the standard stimulus, the peak latency of phase coherence at ß and α frequencies was consistent with that of the N1 component. The inter-trial phase coherence at ß frequency (ß-ITC)served as a faster indicator for detecting frequency transition when the stimulus frequency was changed relative to the standard stimulus. ß-ITC demonstrates temporal stability when detecting pure sinusoidal tones and their frequency changes, and is less susceptible to interference from other neural activities. The phase coherence at θ frequency could integrate the frequency and temporal characteristics of deviant into a single representation, which can be compared with the memory trace formed by the standard stimulus, thus effectively identifying auditory changes. Pure sinusoidal tone stimulation could induce higher inter-trial phase coherence in a smaller time window, but chirp sounds with a fine time-frequency structure required longer latencies to achieve phase coherence. Conclusion: Phase coherence at theta, alpha, and beta frequencies are all involved in auditory change detection, but play different roles in this automatic process. Complex time-frequency modulated stimuli require longer processing time for effective change detection.

[Audiological phenotypes of KBG syndrome: a case report and literatures review].

KBG syndrome is an uncommon autosomal dominant inheritance disease involving multiple systems caused by mutations of ANKRD11 gene. The patient, who has a series of symptoms including hearing loss, short stature, macrodontia of upper central incisors and mental retardation, was diagnosed with KBG syndrome. Pure tone audiometry showed bilateral conductive hearing loss, the temporal bone CT suggested there were deformed ossicular chain in bilateral middle ears, and X-ray showed bone age was only five years old or so, what is the most important is that genetic testing prompted a de novo mutation of ANKRD11. The aim of this article was to briefly analyze the audiological phenotypic characteristics of KBG syndrome and hope to improve the clinical attention to this disease.

Clinical Effect of Bushen Huoxue Method Combined with Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis and Its Effect on IL-1, IL-6, VEGF, and PGE-2.

Objective: To observe the clinical efficacy of the Bushen Huoxue method combined with platelet-rich plasma (PRP) in the treatment of knee osteoarthritis (KOA) and its effect on serum and joint fluid interleukin-1 (IL-1), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE-2). Methods: A total of 64 cases of KOA diagnosed and treated from January 2020 to January 2021 were randomly divided into research group and control group, with 32 cases in each group. The control group was treated with PRP, and the research group took the prescription of the Bushen Huoxue method on the basis of the control group. The clinical efficacy was assessed according to the criteria in "the diagnosis and Treatment of osteoarthritis," osteoarthritis index score and pain visual analogue score (VAS). Serum and articular fluid VAS, IL-1, IL-6, VEGF, and PGE-2 levels were detected by the enzyme-linked immunosorbent assay (ELISA). Results: The clinical effective rate of the research group was 93.8%, which was significantly higher than that of the control group (90.6%). There was no significant difference in the scores of osteoarthritis index between the two groups before treatment, but the scores of both groups decreased after treatment and was lower in the research group than those in the control group. VAS was significantly decreased in two groups after treatment and it was lower in the research group than that in the control group. After treatment, the levels of IL-1, IL-6, and PGE-2 in serum and articular fluid all indexes were decreased, and the levels in the research group were lower than those in the control group. Conclusions: PRP joint cavity injection combined with oral administration of Bushen Huoxue prescription, and PRP joint cavity injection alone can improve the efficacy of KOA, relieve knee pain, and promote the recovery of knee function. The mechanism may be related to the reduction of IL-1, IL-6, VEGF levels, and PGE-2 levels in the serum and joint fluid. However, the efficacy of combination therapy was superior to PRP alone.

Effect of anemia and erythrocyte indices on hemoglobin A1c levels among pregnant women.

BACKGROUND: Anemia is a common disorder among pregnant women; however, the effect of anemia on hemoglobin A1c (HbA1c) levels has not been adequately explored. We aim to examine the influence of anemia on the HbA1c concentration and investigate the relationship between erythrocyte indices and HbA1c levels during pregnancy. METHODS: We performed a retrospective analysis of 1369 pregnant Chinese women. The clinical and analytical data were collected. Independent t-test and Analysis of Variance were used for comparative studies, and multiple linear regression analysis was used to identify the association between erythrocyte indices and HbA1c. RESULTS: The differences in HbA1c between non-anemia and mild anemia were negligible, and the differences in HbA1c between non-anemia and moderate anemia were well within the allowable variability for clinical practice (≥0.5% absolute changes). Mean corpuscular hemoglobin (MCH) correlated with HbA1c significantly, independent of pregnancy, trimester, and anemia. The distinction of HbA1c levels between grades of Hb became no significant (P = 0.955), while differences between trimesters persisted after adjusting for MCH. CONCLUSION: Mild and moderate anemia should not be the primary concern when using HbA1c to monitor blood glucose in pregnancy. MCH showed negative correlations with HbA1c independently, suggesting a previously unknown mechanism affecting HbA1c levels.

Extraction Optimization, Structural Characterization, and Anti-Hepatoma Activity of Acidic Polysaccharides From Scutellaria barbata D. Don.

The Chinese medicinal herb Scutellaria barbata D. Don has antitumour effects and is used to treat liver cancer in the clinic. S. barbata polysaccharide (SBP), one of the main active components extracted from S. barbata D. Don, exhibits antitumour activity. However, there is still a lack of research on the extraction optimization, structural characterization, and anti-hepatoma activity of acidic polysaccharides from S. barbata D. Don. In this study, the optimal extraction conditions for SBP were determined by response surface methodology (RSM): the material-liquid ratio was 1:25, the extraction time was 2 h, and the extraction temperature was 90°C. Under these conditions, the average extraction efficiency was 3.85 ± 0.13%. Two water-soluble polysaccharides were isolated from S. barbata D. Don, namely, SBP-1A and SBP-2A, these homogeneous acidic polysaccharide components with average molecular weights of 1.15 × 105 Da and 1.4 × 105 Da, respectively, were obtained at high purity. The results showed that the monosaccharide constituents of the two components were fucose, galactosamine hydrochloride, rhamnose, arabinose, glucosamine hydrochloride, galactose, glucose, xylose, and mannose; the molar ratio of these constituents in SBP-1A was 0.6:0.3:0.6:30.6:3.3:38.4:16.1:8:1.4, and that in SBP-2A was 0.6:0.5:0.8:36.3:4.4:42.7:9.2:3.6:0.7. In addition, SBP-1A and SBP-2A contained uronic acid and ß-glucan, and the residue on the polysaccharide was mainly pyranose. The in vitro results showed that the anti-hepatoma activity of SBP-2A was better than that of SBP-1A and SBP. In addition, SBP-2A significantly enhanced HepG2 cell death, as cell viability was decreased, and SBP-2A induced HepG2 cell apoptosis and blocked the G1 phase. This phenomenon was coupled with the upregulated expression of P53 and Bax/Bcl-2 ratio, as well as the downregulated expression of the cell cycle-regulating protein cyclinD1, CDK4, and Bcl-2 in this study. Further analysis showed that 50 mg/kg SBP-2A inhibited the tumour growth in H22 tumour-bearing mice, with an average inhibition rate of 40.33%. Taken together, SBP-2A, isolated and purified from S. barbata showed good antitumour activity in vivo and in vitro, and SBP-2A may be a candidate drug for further evaluation in cancer prevention. This study provides insight for further research on the molecular mechanism of the anti-hepatoma activity of S. barbata polysaccharide.

Using deep learning method to identify left ventricular hypertrophy on echocardiography.

BACKGROUND: Left ventricular hypertrophy (LVH) is an independent prognostic factor for cardiovascular events and it can be detected by echocardiography in the early stage. In this study, we aim to develop a semi-automatic diagnostic network based on deep learning algorithms to detect LVH. METHODS: We retrospectively collected 1610 transthoracic echocardiograms, included 724 patients [189 hypertensive heart disease (HHD), 218 hypertrophic cardiomyopathy (HCM), and 58 cardiac amyloidosis (CA), along with 259 controls]. The diagnosis of LVH was defined by two experienced clinicians. For the deep learning architecture, we introduced ResNet and U-net++ to complete classification and segmentation tasks respectively. The models were trained and validated independently. Then, we connected the best-performing models to form the final framework and tested its capabilities. RESULTS: In terms of individual networks, the view classification model produced AUC = 1.0. The AUC of the LVH detection model was 0.98 (95% CI 0.94-0.99), with corresponding sensitivity and specificity of 94.0% (95% CI 85.3-98.7%) and 91.6% (95% CI 84.6-96.1%) respectively. For etiology identification, the independent model yielded good results with AUC = 0.90 (95% CI 0.82-0.95) for HCM, AUC = 0.94 (95% CI 0.88-0.98) for CA, and AUC = 0.88 (95% CI 0.80-0.93) for HHD. Finally, our final integrated framework automatically classified four conditions (Normal, HCM, CA, and HHD), which achieved an average of AUC 0.91, with an average sensitivity and specificity of 83.7% and 90.0%. CONCLUSION: Deep learning architecture has the ability to detect LVH and even distinguish the latent etiology of LVH.

Mechanism of Action of Periplogenin on Nasopharyngeal Carcinoma Based on Network Pharmacology and Experimental Study of Vitamin E Coupled with Periplogenin Self-Assembled Nano-Prodrug for Nasopharyngeal Carcinoma.

Periplogenin is a compound extracted from cortex periplocae. In the monomers' screening for inhibiting nasopharyngeal carcinoma, we found that periplogenin can inhibit nasopharyngeal carcinoma; however, its mechanism is still unclear. In this study, the chemical structure of periplogenin was uploaded to the PubChem database in order to obtain the target of periplogenin. The NPC's differential genes were obtained by analyzing the nasopharyngeal carcinoma data in the GEO database by R software. The common target of periplogenin and nasopharyngeal carcinoma was obtained through Cytoscape. Through R software analysis, ALB, epidermal growth factor receptor (EGFR), MAPK1, ESR1, MAPK8, SRC, CASP3, HSP90AA1, AR, MAPK14 may be the main targets of periplogenin in NPC. Through go enrichment analysis, it was found that periplogenin acted mainly on nasopharyngeal carcinoma through response to steroid metabolic process, cellular response to steroid hormone stimulus, hormone-mediated, and steroid hormone signaling pathway. After enrichment analysis on the Kyoto Encyclopedia of Genes and Genomes pathway, it was found that periplocan may inhibit NPC through the MAPK signaling pathway (the main signaling pathway), and the signaling pathway of proteoglycans in cancer, and the PI3K/AKT signaling pathway as well. In this study, we also carried out the experimental study of vitamin E together with periplogenin self-assembled nano-prodrugs in the treatment of NPC, and the results showed that tumor weight of PBS group was 0.531±0.039 g, while that of PPG group and MPSSV-NPs group was 0.258±0.059 g and 0.169±0.033 g, respectively, which was lower than PBS group. And the tumor inhibition rate of MPSSV-NPs was 69.41%, which was significantly higher than that of the PPG group (51.38%). This study demonstrated the mechanism of inhibition of nasopharyngeal carcinoma (NPC) by the monomer of periplogenin based on network pharmacology. We preliminarily confirmed that vitamin E coupled with a periplogenin self-assembled nano-prodrug has obvious effect in treating nasopharyngeal carcinoma.

Cardiovascular dysfunction in offspring of ovarian-hyperstimulated women and effects of estradiol and progesterone: a retrospective cohort study and proteomics analysis.

CONTEXT: The cardiovascular dysfunction in children born with assisted reproductive technologies has been of great concern. However, the association of ovarian hyperstimulation syndrome (OHSS), a complication of assisted reproductive technologies, with worse cardiovascular functions and underlying mechanism remains unknown. OBJECTIVES: The objective of the study was to assess the cardiovascular functions of children born to mothers with OHSS and investigate the underlying regulator(s). DESIGN AND SETTING: This was a retrospective cohort recruited in a university hospital. PARTICIPANTS AND METHODS: We assessed the cardiovascular functions by Doppler echography in 42 children born to OHSS women, 34 children of mothers with non-OHSS in vitro fertilization, and 48 spontaneously conceived (SC) children (mean age ∼ 4.5 y). Groups were matched for gestational age at delivery and birth weight. An isobaric tag for relative and absolute quantitation-labeled proteomics analysis was performed with another set of umbilical arteries from OHSS and SC pregnancies (n = 3 for both groups). RESULTS: Children of OHSS mothers showed a significantly decreased mitral ratio of early to late mitral peak velocities, reduced systolic and diastolic diameters of common carotid arteries, and impaired flow-mediated dilation compared with non-OHSS in vitro fertilization and SC children. Intima-media thickness and arterial stiffness indices were similar in the three groups. In the proteomics study, 1640 proteins were identified from OHSS and SC umbilical arteries, and 40 differentially expressed proteins were selected for further analysis. Estradiol and progesterone were identified as activated upstream regulators. CONCLUSIONS: Children born to ovarian-hyperstimulated women displayed cardiovascular dysfunctions. The underlying mechanisms may involve the effects of supraphysiological estradiol and progesterone levels.