Acetylshikonin induces apoptosis through the endoplasmic reticulum stress-activated PERK/eIF2α /CHOP axis in oesophageal squamous cell carcinoma.

Acetylshikonin (AS) is an active component of Lithospermum erythrorhizon Sieb. et Zucc that exhibits activity against various cancers; however, the underlying mechanisms of AS against oesophageal squamous carcinoma (ESCC) need to be elusive. The research explores the anti-cancer role and potential mechanism of AS on ESCC in vitro and in vivo, providing evidences for AS treatment against ESCC. In this study, we firstly demonstrated that AS treatment effectively inhibits cell viability and proliferation of ESCC cells. In addition, AS significantly induces G1/S phage arrest and promotes apoptosis in ESCC cell lines. Further studies reveal that AS induces ER stress, as observed by dose- and time-dependently increased expression of BIP, PDI, PERK, phosphorylation of eIF2α , CHOP and splicing of XBP1. CHOP knockdown or PERK inhibition markedly rescue cell apoptosis induced by AS. Moreover, AS treatment significantly inhibits ESCC xenograft growth in nude mice. Elevated expression of BIP and CHOP is also observed in xenograft tumours. Taken together, AS inhibits proliferation and induces apoptosis through ER stress-activated PERK/eIF2α /CHOP pathway in ESCC, which indicates AS represents a promising candidate for ESCC treatment.

The MYB family and their response to abiotic stress in ginger (Zingiber officinale Roscoe).

BACKGROUND: Zingiber officinale Roscoe, colloquially known as ginger, is a crop of significant medicinal and culinary value that frequently encounters adversity stemming from inhospitable environmental conditions. The MYB transcription factors have garnered recognition for their pivotal role in orchestrating a multitude of plant biological pathways. Nevertheless, the enumeration and characterization of the MYBs within Z. officinale Roscoe remains unknown. This study embarks on a genome-wide scrutiny of the MYB gene lineage in ginger, with the aim of cataloging all ZoMYB genes implicated in the biosynthesis of gingerols and curcuminoids, and elucidating their potential regulatory mechanisms in counteracting abiotic stress, thereby influencing ginger growth and development. RESULTS: In this study, we identified an MYB gene family comprising 231 members in ginger genome. This ensemble comprises 74 singular-repeat MYBs (1R-MYB), 156 double-repeat MYBs (R2R3-MYB), and a solitary triple-repeat MYB (R1R2R3-MYB). Moreover, a comprehensive analysis encompassing the sequence features, conserved protein motifs, phylogenetic relationships, chromosome location, and gene duplication events of the ZoMYBs was conducted. We classified ZoMYBs into 37 groups, congruent with the number of conserved domains and gene structure analysis. Additionally, the expression profiles of ZoMYBs during development and under various stresses, including ABA, cold, drought, heat, and salt, were investigated in ginger utilizing both RNA-seq data and qRT-PCR analysis. CONCLUSION: This work provides a comprehensive understanding of the MYB family in ginger and lays the foundation for the future investigation of the potential functions of ZoMYB genes in ginger growth, development and abiotic stress tolerance of ginger.

Parallel CNN-Deep Learning Clinical-Imaging Signature for Assessing Pathologic Grade and Prognosis of Soft Tissue Sarcoma Patients.

BACKGROUND: Traditional biopsies pose risks and may not accurately reflect soft tissue sarcoma (STS) heterogeneity. MRI provides a noninvasive, comprehensive alternative. PURPOSE: To assess the diagnostic accuracy of histological grading and prognosis in STS patients when integrating clinical-imaging parameters with deep learning (DL) features from preoperative MR images. STUDY TYPE: Retrospective/prospective. POPULATION: 354 pathologically confirmed STS patients (226 low-grade, 128 high-grade) from three hospitals and the Cancer Imaging Archive (TCIA), divided into training (n = 185), external test (n = 125), and TCIA cohorts (n = 44). 12 patients (6 low-grade, 6 high-grade) were enrolled into prospective validation cohort. FIELD STRENGTH/SEQUENCE: 1.5 T and 3.0 T/Unenhanced T1-weighted and fat-suppressed-T2-weighted. ASSESSMENT: DL features were extracted from MR images using a parallel ResNet-18 model to construct DL signature. Clinical-imaging characteristics included age, gender, tumor-node-metastasis stage and MRI semantic features (depth, number, heterogeneity at T1WI/FS-T2WI, necrosis, and peritumoral edema). Logistic regression analysis identified significant risk factors for the clinical model. A DL clinical-imaging signature (DLCS) was constructed by incorporating DL signature with risk factors, evaluated for risk stratification, and assessed for progression-free survival (PFS) in retrospective cohorts, with an average follow-up of 23 ± 22 months. STATISTICAL TESTS: Logistic regression, Cox regression, Kaplan-Meier curves, log-rank test, area under the receiver operating characteristic curve (AUC)，and decision curve analysis. A P-value <0.05 was considered significant. RESULTS: The AUC values for DLCS in the external test, TCIA, and prospective test cohorts (0.834, 0.838, 0.819) were superior to clinical model (0.662, 0.685, 0.694). Decision curve analysis showed that the DLCS model provided greater clinical net benefit over the DL and clinical models. Also, the DLCS model was able to risk-stratify patients and assess PFS. DATA CONCLUSION: The DLCS exhibited strong capabilities in histological grading and prognosis assessment for STS patients, and may have potential to aid in the formulation of personalized treatment plans. TECHNICAL EFFICACY: Stage 2.

Moraxella haemolytica sp. nov., isolated from a goat with respiratory disease.

An aerobic, haemolytic, Gram-negative and rod-shaped bacterial strain ZY171148T was isolated from the lung of a dead goat with respiratory disease in Southwest China. The strain grew at 24-39 °C, at pH 6.0-9.0 and in the presence of 0.5-2.0% (w/v) NaCl. Phylogenetic analysis of 16S rRNA gene sequences showed that the strain belongs to the genus Moraxella. The nucleotide sequence similarity analysis of the 16S rRNA gene showed that the strain has the highest similarity of 98.1% to Moraxella (M.) caprae ATCC 700019 T. Phylogenomic analysis of 800 single-copy protein sequences indicated that the strain is a member of the genus Moraxella and forms a separated branch on the Moraxella phylogenetic tree. The strain exhibited the highest orthologous average nucleotide identity (OrthoANI) and average amino acid identity (AAI) values of 77.0 and 77.9% to M. nasibovis CCUG 75921T and M. ovis CCUG 354T, respectively. The strain shared the highest digital DNA-DNA hybridization (dDDH) value of 26.2% to M. osloensis CCUG 350T. The genome G + C content of strain ZY171148T was 42.6 mol%. The strain had C18:1 ω9c (41.7%), C18:0 (11.2%), C16:0 (14.1%) and C12:0 3OH (9.7%) as the predominant fatty acids and CoQ-8 as the major respiratory quinone. The strain contained phosphatidylglycerol, phosphatidylethanolamine, cardiolipin, dilysocardiolipin, monolysocardiolipin and phosphatidic acid as the major polar lipids. ß-haemolysis was observed on Columbia blood agar. All results confirmed that strain ZY171148T represents a novel species of the genus Moraxella, for which the name Moraxella haemolytica sp. nov. is proposed, with strain ZY171148T = CCTCC AB 2021471T = CCUG 75920T as the type strain.

A nomogram model for assessing predictors and prognosis of postoperative delirium in patients receiving acute type A aortic dissection surgery.

BACKGROUND: Postoperative delirium (POD) complicates the postoperative course. There is limited information on POD-related risk factors (RFs) and prognosis in patients with acute type A aortic dissection (ATAAD) after modified triple-branched stent graft implantation (MTBSG) surgery. METHODS: We retrospectively examined consecutive ATAAD patients who received MTBSG surgery in our hospital between January 2013 and December 2019. We employed univariate and multivariate analyses to identify stand-alone RFs for POD. A nomogram was next generated to estimate POD occurrence. The primary outcome was the development of POD, and the secondary outcomes were intensive care unit (ICU) and hospital stays, hospitalization costs, and in-hospital and follow-up mortality. RESULTS: We selected 692 patients, of whom 220 experienced POD (31.8%). Based on our analysis, the following factors enhanced the likelihood of POD development: alcohol consumption (p < 0.001), acute physiology and chronic health evaluation II score (p = 0.023), serum total bilirubin (p = 0.007), stage 3 acute kidney injury (p < 0.001), serum interleukin-6 (p = 0.031), post-operative analgesics usage (p = 0.015), and ventilation duration (p = 0.008). POD patients had significantly longer ventilator times (p = 0.003), ICU stays (p < 0.001), and hospital stays (p = 0.038), together with increased hospitalization costs (p < 0.001) and in-hospital mortality (p = 0.019). However, POD was not a RF for mortality during follow-up (log-rank p = 0.611). CONCLUSIONS: We demonstrated a strong link between POD and poor prognosis in ATAAD patients. We also constructed a prognosis estimator model which will benefit early management guidance to minimize the incidence of POD.

A YOLO-based AI system for classifying calcifications on spot magnification mammograms.

OBJECTIVES: Use of an AI system based on deep learning to investigate whether the system can aid in distinguishing malignant from benign calcifications on spot magnification mammograms, thus potentially reducing unnecessary biopsies. METHODS: In this retrospective study, we included public and in-house datasets with annotations for the calcifications on both craniocaudal and mediolateral oblique vies, or both craniocaudal and mediolateral views of each case of mammograms. All the lesions had pathological results for correlation. Our system comprised an algorithm based on You Only Look Once (YOLO) named adaptive multiscale decision fusion module. The algorithm was pre-trained on a public dataset, Curated Breast Imaging Subset of Digital Database for Screening Mammography (CBIS-DDSM), then re-trained and tested on the in-house dataset of spot magnification mammograms. The performance of the system was investigated by receiver operating characteristic (ROC) analysis. RESULTS: We included 1872 images from 753 calcification cases (414 benign and 339 malignant) from CBIS-DDSM. From the in-house dataset, 636 cases (432 benign and 204 malignant) with 1269 spot magnification mammograms were included, with all lesions being recommended for biopsy by radiologists. The area under the ROC curve for our system on the in-house testing dataset was 0.888 (95% CI 0.868-0.908), with a sensitivity of 88.4% (95% CI 86.9-8.99%), specificity of 80.8% (95% CI 77.6-84%), and an accuracy of 84.6% (95% CI 81.8-87.4%) at the optimal cutoff value. Using the system with two views of spot magnification mammograms, 80.8% benign biopsies could be avoided. CONCLUSION: The AI system showed good accuracy for classification of calcifications on spot magnification mammograms which were all categorized as suspicious by radiologists, thereby potentially reducing unnecessary biopsies.

Blockade of endocannabinoid system by oxytocin attenuates memory deficits in oxycodone-treated rats.

Oxycodone is a highly prescribed opioid and its abuse has been rampant. Accumulating evidence shows that the cannabinoid CB1 receptor (CB1R) plays a key role in mediating rewarding effects to opioids. However, the downstream signalling of CB1R induced by oxycodone remains unclear. The neuropeptide oxytocin is well known as a potential remedy for drug addiction. Thus, our study aims to explore the mechanism of oxycodone-induced learning and memory deficits underlying the endocannabinoid system (ECS) and the effect of oxytocin. Rats were intraperitoneally injected with oxycodone once a day for eight consecutive day. Novel object recognition, resident-intruder and Morris Water Maze tests were employed to assess the cognitive, social and spatial memory of the rats after oxycodone withdrawal. The (co-)expression of CB1R, cyclin-dependent kinase 5 (Cdk5), regulatory protein p25, tau and phosphorylated tau was measured 1 day after the last behavioural test. The histopathological staining and synaptic density in the hippocampus were observed as well. We found that oxycodone upregulated the expression of p-GSK3ß, co-expression of p-Cdk5 and p25 through CB1R. This finding was accompanied by elevation of pSer396, pSer404 in the tau, and reduction of the number of neurons, dendritic spines and synaptic density in the hippocampus. Furthermore, i.c.v. treatment with oxytocin ameliorates memory deficits in oxycodone-treated rats through inhibition of the ECS. We propose further studies on the clinical use of this neuropeptide, which may potentially cure drug addiction.

Altered dynamic brain activity and its association with memory decline after night shift-related sleep deprivation in nurses.

AIMS AND OBJECTIVES: To investigate, for the first time, aberrant time-varying local brain activity in nurses following night shift-related sleep deprivation (SD) and its association with memory decline. BACKGROUND: Prior studies have elucidated alterations in static local brain activity resulting from SD in the occupations outside medical profession. DESIGN: A longitudinal study followed the STROBE recommendations. METHODS: Twenty female nurses underwent resting-state functional magnetic resonance imaging and memory function assessment (by Complex Figure Test (CFT) and the California Verbal Learning Test, Second Edition (CVLT-II)) twice, once in a rested wakefulness (RW) state and another after SD. By combining the sliding-window approach and amplitude of low-frequency fluctuation (ALFF) analysis, the dynamic ALFF (dALFF) variability was calculated to reflect the characteristics of dynamic local brain activity. RESULTS: Poor performance on the CFT and CVLT-II was observed in nurses with night shift-related SD. Reduced dALFF variability was found in a set of cognition-related brain regions (including the medial/middle/superior frontal gyrus, anterior/posterior cingulate gyrus, precuneus, angular gyrus, orbitofrontal and subgenual areas, and posterior cerebellum lobe), while increased dALFF variability was observed in the somatosensory-related, visual and auditory regions. SD-related dALFF variability alterations correlated with changes in subjects' performance on the CFT and CVLT-II. CONCLUSIONS: Night shift-related SD disturbed dynamic brain activity in high cognitive regions and induced compensatory reactions in primary perceptual cortex. Identifying dALFF variability abnormalities may broaden our understanding of neural substrates underlying SD-related cognitive alterations, especially memory dysfunction. RELEVANCE TO CLINICAL PRACTICE: Night shift-related SD is as an important occupational hazard affecting brain function in nurses. The effective countermeasure addressing the adverse outcomes of SD should be advocated for nurses. PATIENT OR PUBLIC CONTRIBUTION: Patients or public were not involved in the design and implementation of the study or the analysis and interpretation of the data.

[Frequency-Specific Alterations of Spontaneous Brain Activity in First-Episode Drug-Naïve Schizophrenia].

Objective: To investigate frequency-specific alterations of spontaneous brain activity in first-episode drug-naïve schizophrenia (SZ) patients and the associations with clinical symptoms. Methods: We collected the resting-state functional MRI (rs-fMRI) data from 84 first-episode drug-naïve SZ patients and 94 healthy controls (HCs) and calculated the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) of four frequency bands, including slow-2, slow-3, slow-4, and slow-5. Two-sample t-tests were used to evaluate the intergroup differences in ALFF and ReHo, while partial correlation analyses were conducted to explore the associations between abnormal ALFF and ReHo and the severity of clinical symptoms in the SZ group. Results: Compared with HCs, the SZ group showed reduced ALFF in superior cerebellum and cerebellar vermis across slow-2, slow-3, and slow-4 bands, while increased ALFF was found in left superior temporal gyrus, middle temporal gyrus, and superior temporal pole at slow-4 band. Moreover, reduced ReHo was observed in the right precentral and postcentral gyri at slow-3 band in the SZ group. Additionally, the ALFF of left superior temporal gyrus, middle temporal gyrus, and superior temporal pole in slow-4 band showed a trend of positive correlation with the excited factor score of Positive and Negative Syndrome Scale (PANSS) in the SZ group. Conclusion: Our results suggest that local alterations of spontaneous brain activity were frequency-specific in first-episode drug-naïve SZ patients.

Effects of qufeng xuanfei formula in guinea pig model of airway hyperergy.

This work aimed to clarify the potential regulating effects of Qufeng Xuanfei formula (QFXF) on airway neurogenic inflammation and its underlying target signal pathway. Guinea pig model of airway hyperergy (AHR) was used. The relative susceptibility of major proteins to airway neurogenic inflammation was assessed using Western blot immunoassay followed by being separated by SDS-PAGE. Compared to the model group, QFXF of all concentrations effectively depressed the capsaicin enhanced cough in guinea pigs and the peak values of airway resistance significantly decreased. The results illustrated that QFXF alleviated cough symptom in guinea pigs and reduced airway neurogenic inflammation when compared to AHR model group. Airway inflammation and damage, as well as the levels of NGF, SP and c-Fos in QFXF decreased the most in the high-dose group. The mechanism of antitussive activity may be associated with reducing airway inflammation. QFXF displayed effect on chronic cough through reducing the levels of neuropeptides, attenuating airway inflammation and promoting recovery from disease to decrease the airway neuro sensitivity, suggesting that the potential mechanism may be related to Ras/ERK/c-Fos pathway.

Discovery of N-(1,3,4-thiadiazol-2-yl)benzamide derivatives containing a 6,7-methoxyquinoline structure as novel EGFR/HER-2 dual-target inhibitors against cancer growth and angiogenesis.

Targeting EGFR and HER-2 is an essential direction for cancer treatment. Here, a series of N-(1,3,4-thiadiazol-2-yl)benzamide derivatives containing a 6,7-methoxyquinoline structure was designed and synthesized to serve as EGFR/HER-2 dual-target inhibitors. The kinase assays verified that target compounds could inhibit the kinase activity of EGFR and HER-2 selectively. The results of CCK-8 and 3D cell viability assays confirmed that target compounds had excellent anti-proliferation ability against breast cancer cells (MCF-7 and SK-BR-3) and lung cancer cells (A549 and H1975), particularly against SK-BR-3 cells, while the inhibitory effect on healthy breast cells (MCF-10A) and lung cells (Beas-2B) was weak. Among them, the hit compound YH-9 binded to EGFR and HER-2 stably in molecular dynamics studies. Further studies found thatYH-9could induce the release of cytochrome c and inhibit proliferation by promoting ROS expression in SK-BR-3 cells. Moreover,YH-9could diminish the secretion of VEGF and bFGF factors in SK-BR-3 cells, then inhibited tube formation and angiogenesis. Notably,YH-9could effectively inhibit breast cancer growth and angiogenesis with little toxicity in the SK-BR-3 cell xenograft model. Taken together,in vitroandin vivoresults revealed that YH-9 had high drug potential as a dual-target inhibitor of EGFR/HER-2 to inhibit breast cancer growth and angiogenesis.

Clinical validation of the use of prototype software for automatic cartilage segmentation to quantify knee cartilage in volunteers.

BACKGROUND: The cartilage segmentation algorithms make it possible to accurately evaluate the morphology and degeneration of cartilage. There are some factors (location of cartilage subregions, hydrarthrosis and cartilage degeneration) that may influence the accuracy of segmentation. It is valuable to evaluate and compare the accuracy and clinical value of volume and mean T2* values generated directly from automatic knee cartilage segmentation with those from manually corrected results using prototype software. METHOD: Thirty-two volunteers were recruited, all of whom underwent right knee magnetic resonance imaging examinations. Morphological images were obtained using a three-dimensional (3D) high-resolution Double-Echo in Steady-State (DESS) sequence, and biochemical images were obtained using a two-dimensional T2* mapping sequence. Cartilage score criteria ranged from 0 to 2 and were obtained using the Whole-Organ Magnetic Resonance Imaging Score (WORMS). The femoral, patellar, and tibial cartilages were automatically segmented and divided into subregions using the post-processing prototype software. Afterwards, all the subregions were carefully checked and manual corrections were done where needed. The dice coefficient correlations for each subregion by the automatic segmentation were calculated. RESULTS: Cartilage volume after applying the manual correction was significantly lower than automatic segmentation (P < 0.05). The percentages of the cartilage volume change for each subregion after manual correction were all smaller than 5%. In all the subregions, the mean T2* relaxation time within manual corrected subregions was significantly lower than in regions after automatic segmentation (P < 0.05). The average time for the automatic segmentation of the whole knee was around 6 min, while the average time for manual correction of the whole knee was around 27 min. CONCLUSIONS: Automatic segmentation of cartilage volume has a high dice coefficient correlation and it can provide accurate quantitative information about cartilage efficiently without individual bias. Advances in knowledge: Magnetic resonance imaging is the most promising method to detect structural changes in cartilage tissue. Unfortunately, due to the structure and morphology of the cartilages obtaining accurate segmentations can be problematic. There are some factors (location of cartilage subregions, hydrarthrosis and cartilage degeneration) that may influence segmentation accuracy. We therefore assessed the factors that influence segmentations error.

[Effects of Xiangqin Jiere Granules on lipid metabolism and chronic inflammation in different obesity model mice].

This paper aims to study the effect of Xiangqin Jiere Granules(XQ) on lipid metabolism and chronic inflammation in different obesity model mice. The monosodium glutamate(MSG) obese mouse model was established by subcutaneous injection of MSG in newborn mice, and the high fat diet(HFD) obese mouse model was established by feeding adult mice with HFD. The normal mice were assigned into the control group; the MSG obese mice were assigned into MSG model group, XQ4.5 group(Xiangqin Jiere Granu-les, 4.5 g·kg~(-1)), XQ22.5 group(Xiangqin Jiere Granules, 22.5 g·kg~(-1)); the HFD obese mice were assigned into HFD model group, XQ4.5 group, and XQ22.5 group. The mice were intragastrically administrated with saline or XQ for 5 weeks. After that, the body weight, visceral fat mass, liver and thymus weight, and the organ indexes in each group were measured. The levels of triglyceride(TG), total cholesterol(TC), and low-density lipoprotein cholesterol(LDL-c) in serum and liver tissue were detected by the kits. The mRNA expression levels of acetyl CoA carboxylase 1(ACC1), fatty acid synthetase(FAS), diacylgycerol acyltransferase 1(DGAT1) and hepatic lipase(HTGL) involved in lipid metabolism in mouse liver tissue were detected by quantitative real-time PCR(qPCR). The protein levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in serum were detected by ELISA, and the mRNA levels of TNF-α and IL-6 in liver tissue were detected by qPCR. Compared with the control group, MSG and HFD mice showed increased body weight, abdominal circumference, Lee index and visceral fat mass as well as elevated levels of TG, TC, and LDL-c in serum. The model mice had up-regulated gene levels of ACC1, FAS and DGAT1 while down-regulated gene level of HTGL in the liver. Furthermore, the mRNA and protein levels of IL-6 increased in the model mice. Compared with the model mice, XQ treatment decreased the body weight, abdominal circumference, Lee index, and visceral fat mass, lowered the levels of TG, TC, and LDL-c in se-rum, down-regulated the gene levels of ACC1, FAS, and DGAT1 in liver tissue, up-regulated the gene level of HTGL, and down-regulated the mRNA and protein levels of IL-6. To sum up, XQ has good therapeutic effect on different obesity model mice. It can improve lipid metabolism and reduce fat accumulation in obese mice by regulating the enzymes involved in lipid metabolism, and alleviate obesity-related chronic low-grade inflammation.

[Germplasm resource evaluation of Chrysanthemi Indici Flos based on color and chemical components].

This study explored the correlation between color and chemical components of Chrysanthemi Indici Flos(CIF), aiming at providing a reference for its procurement, evaluation, and breeding. Colorimeter and ultra-performance liquid chromatograph(UPLC) were used to determine the color(lightness-shade chromaticity value L~*, red-green chromaticity value a~*, yellow-blue chromati-city value b~*) and chemical components(cynaroside, linarin, luteolin, apigenin, and chlorogenic acid) of 84 CIF germplasms, respectively. Diversity analysis, correlation analysis, regression analysis, and cluster analysis were performed. The results showed that the color and chemical components of CIF were diversified. Chlorogenic acid was in significantly positive correlation with L~* and b~* and significantly negative correlation with a~*. Cynaroside and grey relational grade γ_i of chemical components were in significantly po-sitive correlation with b~* and L~*, respectively, whereas linarin, luteolin, and apigenin had no significant correlation with L~*, a~*, or b~*. The 84 CIF germplasms were clustered into 4 clades. In addition, germplasms in clade Ⅲ had higher γ_i and total color value(E~*_(ab)) than those in other clades, with the best quality and color, and a germplasm with the highest quality, bright yellow color, and highest content of linarin was screened out in this clade. Thus, CIF with bright yellow color had high content of cymaroside and chlorogenic acid and thereby high quality. In summary, the color can be used to quickly predict the quality of CIF. Our results provided data for the evaluation of CIF quality by color and a reference for its procurement and breeding.

Draft Genome Resource of Fusarium oxysporum f. sp. capsici, the Infectious Agent of Pepper Fusarium Wilt.

Fusarium oxysporum f. sp. capsici is the specific pathogen of pepper Fusarium wilt and causes a significant reduction in pepper yield. Its narrow host specificity has led to the concept of formae speciales. This interesting phenomenon has great potential and needs to be analyzed at the molecular level. In this study, we obtained the draft genome sequence of F. oxysporum f. sp. capsici, using the Oxford Nanopore sequencing technology. The long read-based assembly consisted of 34 contigs, with a total length of 54,516,562 bp. The contig N50 was 4,962,668 bp and the GC content was 47.6%. Our genome assembly of F. oxysporum f. sp. capsici provides a valuable resource for the study of pepper Fusarium wilt, and the comparative genomic study of F. oxysporum.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Skip participates in formation and lipid metabolism of beige adipose and might mediate the effects of SIRT1 activator BTM-0512 on beige remodeling.

Dissipating energy by activating thermogenic adipose to combating obesity attracts many interests. Ski-interacting protein (Skip) has been known to play an important role in cell proliferation and differentiation, but whether it participates in energy metabolism is not known. Our previous study revealed that BTM-0512 could induce beige adipose formation, accompanying with up-regulation of Skip, but the role of Skip in metabolism was unknown. In this study, we mainly investigated whether Skip was involved in beige remodeling of subcutaneous white preadipocytes as well as in lipid metabolism of differentiated beige adipocytes. The results showed that in high fat diet-induced obesity mice, the protein levels of Skip in subcutaneous and visceral white adipose as well as in brown adipose were all down-regulated, especially in subcutaneous white adipose. Then we cultured subcutaneous adipose derived-stem cells (ADSCs) and found knock-down of Skip (siSkip) inhibited the expressions of thermogenic adipose specific genes including PRDM16 and UCP1 in both undifferentiated ADSCs and differentiated beige adipocytes, which could abolish the effects of BTM-0512 on beige remodeling. We further observed that siSkip affected multiple rate-limiting enzymes in lipid metabolism. The expressions of ACC, GPAT-1, HSL and ATGL were down-regulated, while CPT1α expression was up-regulated by siSkip. The expression of AMPK was also decreased by siSkip. In conclusion, our study demonstrated that Skip might play an important role in the beige remodeling of white adipocytes as well as lipid metabolism of beige adipose.

Oxytocin prevents cue-induced reinstatement of oxycodone seeking: Involvement of DNA methylation in the hippocampus.

Oxycodone is one of the most commonly used analgesics in the clinic. However, long-term use can contribute to drug dependence. Accumulating evidence of changes in DNA methylation after opioid relapse has provided insight into mechanisms underlying drug-associated memory. The neuropeptide oxytocin is reported to be a potential treatment for addiction. The present study sought to identify changes in global and synaptic gene methylation after cue-induced reinstatement of oxycodone conditioned place preference (CPP) and the effect of oxytocin. We analyzed hippocampal mRNA of synaptic genes and also synaptic density in response to oxycodone CPP. We determined the mRNA levels of DNA methyltransferases (Dnmts) and ten-eleven translocations (Tets), observed global 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) levels, and measured DNA methylation status of four synaptic genes implicated in learning and memory (Arc, Dlg1, Dlg4, and Syn1). Both synaptic density and the transcription of 15 hippocampal synaptic genes significantly increased following cue-induced reinstatement of oxycodone CPP. Oxycodone relapse was also related to markedly decreased 5-mC levels and decreased transcription of Dnmt1, Dnmt3a, and Dnmt3b; in contrast, 5-hmC levels and the transcription of Tet1 and Tet3 were increased. Oxycodone exposure induced DNA hypomethylation at the exons of the Arc, Dlg1, Dlg4, and Syn1 genes. Intracerebroventricular (ICV) administration of oxytocin (2.5 µg/µl) specifically blocked oxycodone relapse, possibly by inhibition of Arc, Dlg1, Dlg4, and Syn1 hypomethylation in oxycodone-treated rats. Together, these data indicate the occurrence of epigenetic changes in the hippocampus following oxycodone relapse and the potential role of oxytocin in oxycodone addiction.

Prediction of survival according to kinetic changes of cytokines and hepatitis status following radioembolization with yttrium-90 microspheres.

BACKGROUND/PURPOSE: Yttrium-90 radioembolization (Y90-RE) may exert an immunomodulatory effect on the tumor microenvironment of hepatocellular carcinoma (HCC). Whether the host immune alterations after Y90-RE correlated with outcomes and whether Y90-RE affects viral hepatitis reactivation remains unclear. METHODS: Between July 2014 and July 2015, 18 patients undergoing Y90-RE for HCC were prospectively enrolled. Serum levels of virological markers, cytokines and chemokines were measured at baseline, 2, 4, and 12 weeks after Y90-RE. Factors associated with the clinical outcomes were evaluated. RESULTS: The disease control rate of Y90-RE was 44.4% (8 of 18) at 12 weeks, including 1 case with complete response, 4 cases with partial response, and 3 cases with stable disease. Significant elevation from baseline to week 2 and week 4 were noted in IL-10 level (8.4 ± 33.8, 15.7 ± 31.6, and 16.0 ± 41.7 pg/mL, P = 0.041 and 0.013, respectively) and IP-10 level (113.5 ± 97.8, 189.1 ± 164.4, and 168.6 ± 150.5 pg/mL, P = 0.027 and 0.026, respectively). After Y90-RE, transient HBV reactivation occurred in 2 patients, and 1 out of 3 HCV-infected patients exhibited HCV reactivation. Univariate analysis revealed that lower baseline IP-10 (≤200 pg/mL) and alanine aminotransferase (ALT) (≤50 U/L) levels were associated with better overall survival. Multivariate analysis identified an IP-10 level of 200 pg/mL (HR = 4.374, P = 0.045) as a predictor of overall survival. CONCLUSION: Baseline serum IP-10 level is a predictor of survival for HCC patients undergoing Y90-RE. HBV and HCV reactivation may develop after Y90-RE treatment.

Inhibition of BRD4 triggers cellular senescence through suppressing aurora kinases in oesophageal cancer cells.

Oesophageal cancer is one of the most frequent solid malignancies and the leading cause of cancer-related death around the world. It is urgent to develop novel therapy strategies to improve patient outcomes. Acetylation modification of histones has been extensively studied in epigenetics. BRD4, a reader of acetylated histone and non-histone proteins, has involved in tumorigenesis. It has emerged as a promising target for cancer therapy. BRD4 inhibitors, such as JQ1, have exerted efficacious anti-proliferation activities in diverse cancers. However, the effects of JQ1 on oesophageal cancer are still not fully described. Here, we demonstrate that JQ1 suppresses cell growth and triggers cellular senescence in KYSE450 cells. Mechanistically, JQ1 up-regulates p21 level and decreases cyclin D1 resulting in G1 cycle arrest. The inhibitory effects of JQ1 on KYSE450 cells are independent on apoptosis. It activates cellular senescence by increasing SA-ß-gal activity. BRD4 knockdown by shRNA recapitulates cellular senescence. We also display that administration of JQ1 decreases recruitment of BRD4 on the promoter of aurora kinases A and B. Inhibitors targeting at AURKA/B phenocopy JQ1 treatment in KYSE450 cells. These results identify a novel action manner of BRD4 in oesophageal cancer, which strengthens JQ1 as a candidate drug in oesophageal cancer chemotherapy.

A cost-sensitive online learning method for peptide identification.

BACKGROUND: Post-database search is a key procedure in peptide identification with tandem mass spectrometry (MS/MS) strategies for refining peptide-spectrum matches (PSMs) generated by database search engines. Although many statistical and machine learning-based methods have been developed to improve the accuracy of peptide identification, the challenge remains on large-scale datasets and datasets with a distribution of unbalanced PSMs. A more efficient learning strategy is required for improving the accuracy of peptide identification on challenging datasets. While complex learning models have larger power of classification, they may cause overfitting problems and introduce computational complexity on large-scale datasets. Kernel methods map data from the sample space to high dimensional spaces where data relationships can be simplified for modeling. RESULTS: In order to tackle the computational challenge of using the kernel-based learning model for practical peptide identification problems, we present an online learning algorithm, OLCS-Ranker, which iteratively feeds only one training sample into the learning model at each round, and, as a result, the memory requirement for computation is significantly reduced. Meanwhile, we propose a cost-sensitive learning model for OLCS-Ranker by using a larger loss of decoy PSMs than that of target PSMs in the loss function. CONCLUSIONS: The new model can reduce its false discovery rate on datasets with a distribution of unbalanced PSMs. Experimental studies show that OLCS-Ranker outperforms other methods in terms of accuracy and stability, especially on datasets with a distribution of unbalanced PSMs. Furthermore, OLCS-Ranker is 15-85 times faster than CRanker.