Macrophage KLF15 prevents foam cell formation and atherosclerosis via transcriptional suppression of OLR-1.

BACKGROUND: Macrophage-derived foam cells are a hallmark of atherosclerosis. Scavenger receptors, including lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (OLR-1), are the principal receptors responsible for the uptake and modification of LDL, facilitating macrophage lipid load and the uptake of oxidized LDL by arterial wall cells. Krüppel-like factor 15 (KLF15) is a transcription factor that regulates the expression of genes by binding to the promoter during transcription. Therefore, this study aimed to investigate the precise role of macrophage KLF15 in atherogenesis. METHODS: We used two murine models of atherosclerosis: mice injected with an adeno-associated virus (AAV) encoding the Asp374-to-Tyr mutant version of human PCSK9, followed by 12 weeks on a high-fat diet (HFD), and ApoE-/-- mice on a HFD. We subsequently injected mice with AAV-KLF15 and AAV-LacZ to assess the role of KLF15 in the development of atherosclerosis in vivo. Oil Red O, H&E, and Masson's trichome staining were used to evaluate atherosclerotic lesions. Western blots and RT-qPCR were used to assess protein and mRNA levels, respectively. RESULTS: We determined that KLF15 expression was downregulated during atherosclerosis formation, and KLF15 overexpression prevented atherosclerosis progression. KLF15 expression levels did not affect body weight or serum lipid levels in mice. However, KLF15 overexpression in macrophages prevented foam cell formation by reducing OLR-1-meditated lipid uptake. KLF15 directly targeted and transcriptionally downregulated OLR-1 levels. Restoration of OLR-1 reversed the beneficial effects of KLF15 in atherosclerosis. CONCLUSION: Macrophage KLF15 transcriptionally downregulated OLR-1 expression to reduce lipid uptake, thereby preventing foam cell formation and atherosclerosis. Thus, our results suggest that KLF15 is a potential therapeutic target for atherosclerosis.

Sulfur-Vacancy-Engineered Two-Dimensional Cu@SnS2-x Nanosheets Constructed via Heterovalent Substitution for High-Efficiency Piezocatalytic Tumor Therapy.

Ultrasound (US)-mediated piezocatalytic tumor therapy has attracted much attention due to its notable tissue-penetration capabilities, noninvasiveness, and low oxygen dependency. Nevertheless, the efficiency of piezocatalytic therapy is limited due to an inadequate piezoelectric response, low separation of electron-hole (e--h+) pairs, and complex tumor microenvironment (TME). Herein, an ultrathin two-dimensional (2D) sulfur-vacancy-engineered (Sv-engineered) Cu@SnS2-x nanosheet (NS) with an enhanced piezoelectric effect was constructed via the heterovalent substitution strategy of Sn4+ by Cu2+. The introduction of Cu2+ ion not only causes changes in the crystal structure to increase polarization but also generates rich Sv to decrease band gap from 2.16 to 1.62 eV and inhibit e--h+ pairs recombination, collectively leading to the highly efficient generation of reactive oxygen species under US irradiation. Moreover, Cu@SnS2-x shows US-enhanced TME-responsive Fenton-like catalytic activity and glutathione depletion ability, further aggravating the oxidative stress. Both in vitro and in vivo results prove that the Sv-engineered Cu@SnS2-x NSs can significantly kill tumor cells and achieve high-efficiency piezocatalytic tumor therapy in a biocompatible manner. Overall, this study provides a new avenue for sonocatalytic therapy and broadens the application of 2D piezoelectric materials.

NOTCH3 promotes docetaxel resistance of prostate cancer cells through regulating TUBB3 and MAPK signaling pathway.

Docetaxel is the preferred chemotherapeutic agent in patients with castrate-resistant prostate cancer (CRPC). However, patients eventually develop docetaxel resistance and in the absence of effective treatment options. Consequently, it is essential to investigate the mechanisms generating docetaxel resistance and develop novel alternative therapeutic targets. RNA sequencing was undertaken on docetaxel-sensitive and docetaxel-resistant prostate cancer (PCa) cells. Subsequently, chemoresistance, cancer stemness, and lipid metabolism were investigated. To obtain insight into the precise activities and action mechanisms of NOTCH3 in docetaxel-resistant PCa, immunoprecipitation, mass spectrometry, ChIP, luciferase reporter assay, cell metabolism, and animal experiments were performed. Through RNA sequencing analysis, we found that NOTCH3 expression was markedly higher in docetaxel-resistant cells relative to parental cells, and that this trend was continued in docetaxel-resistant PCa tissues. Experiments in vitro and in vivo revealed that NOTCH3 enhanced stemness, lipid metabolism, and docetaxel resistance in PCa. Mechanistically, NOTCH3 is bound to TUBB3 and activates the MAPK signaling pathway. Moreover, NOTCH3 was directly regulated by MEF2A in docetaxel-resistant cells. Notably, targeting NOTCH3 and the MEF2A/TUBB3 signaling axis was related to docetaxel chemoresistance in PCa. Overall, these results demonstrated that NOTCH3 fostered stemness, lipid metabolism, and docetaxel resistance in PCa via the TUBB3 and MAPK signaling pathways. Therefore, NOTCH3 may be employed as a prognostic biomarker in PCa patients. NOTCH3 could be a therapeutic target for PCa patients, particularly those who have developed docetaxel resistance.

Deubiquitinating enzyme OTUD4 stabilizes RBM47 to induce ATF3 transcription: a novel mechanism underlying the restrained malignant properties of ccRCC cells.

Dysregulation of deubiquitination contributes to various diseases, including cancer, and aberrant expression of deubiquitinating enzymes is involved in carcinoma progression. As a member of the ovarian tumor (OTU) deubiquitinases, OTUD4 is considered a tumor suppressor in many kinds of malignancies. The biological characteristics and mechanisms of OTUD4 in clear cell renal cell carcinoma (ccRCC) remain unclear. The downregulation of OTUD4 in ccRCC was confirmed based on the TCGA database and a validation cohort of 30-paired ccRCC and para-carcinoma samples. Moreover, OTUD4 expression was detected by immunohistochemistry in 50 cases of ccRCC tissues, and patients with lower levels of OTUD4 showed larger tumor size (p = 0.015). TCGA data revealed that patients with high expression of OTUD4 had a longer overall survival rate. In vitro and in vivo studies revealed that downregulation of OTUD4 was essential for tumor cell growth and metastasis in ccRCC, and OTUD4 overexpression inhibited these malignant phenotypes. We further found that OTUD4 sensitized ccRCC cells to Erastin-induced ferroptosis, and ferrostain-1 inhibited OTUD4-induced ferroptotic cell death. Mechanistic studies indicated that OTUD4 functioned as an anti-proliferative and anti-metastasic factor through the regulation of RNA-binding protein 47 (RBM47)-mediated activating transcription factor 3 (ATF3). OTUD4 directly interacted with RBM47 and promoted its stability via deubiquitination events. RBM47 was critical in ccRCC progression by regulating ATF3 mRNA stability, thereby promoting ATF3-mediated ferroptosis. RBM47 interference abolished the suppressive role of OTUD4 overexpression in ccRCC. Our findings provide mechanistic insight into OTUD4 of ccRCC progression and indicate a novel critical pathway OTUD4/RBM47/ATF3 may serve as a potential therapeutic pathway for ccRCC.

Towards sustainable development goals: An analysis of environmental efficiency and the impacts of self-purification capacity across diverse income levels.

The increasing urgency of global environmental degradation, particularly across diverse economic development stages, underscores a critical need for nuanced understanding and targeted strategies to achieve Sustainable Development Goals. Our study examines environmental efficiency trends over 27 years in 163 countries, utilizing greenhouse gases and particulate matter 2.5 as indicators. We address the challenge by developing and applying a two-stage method that combines a hyperbolic distance function with a stochastic meta frontier approach to assess environmental meta-efficiency. The average meta efficiency of these countries is 0.464, which remains at a relatively low level. Our model indicates that the high-income country group needs to reduce greenhouse gas and pollutant emissions by 25% and increase non-fossil energy usage by 33% to improve environmental efficiency. This suggests these countries must transition towards more sustainable energy sources and practices. Moreover, recognizing that existing income grouping inadequately characterizes each country, we use k-means cluster analysis for regrouping, more accurately reflecting individual differences. The regrouping results show that some high-income countries are classified into inactive groups, implying serious environmental problems. Our findings advocate for collaborative and tailored strategies to address these disparities. We conclude that income levels cannot solely drive environmental efficiency but must also consider geographical and climatic factors, which are pivotal in shaping a country's environmental policies and efforts. This approach offers a clearer understanding of current inefficiencies and sets the stage for more informed policy-making that can better address the specific needs and capabilities of different countries.

Molecular Characteristics of an NDM-4 and OXA-181 Co-Producing K51-ST16 Carbapenem-Resistant Klebsiella pneumoniae: Study of Its Potential Dissemination Mediated by Conjugative Plasmids and Insertion Sequences.

The carbapenem-resistant Klebsiella pneumoniae (CRKP) strain GX34 was recovered from the respiratory tract of an elderly male with severe pneumonia, and only susceptible to amikacin, tigecycline, and colistin. Complete genome suggested that it belonged to K51-ST16 and harbored plasmid-encoded NDM-4 and OXA-181, located on IncFIB plasmid GX34p1_NDM-4 and ColKP3/IncX3 plasmid GX34p4_OXA-181, respectively. A series of transconjugants generated in the plasmid conjugation assays, including Escherichia coli J53-N1 (harboring a self-transmissible and blaNDM-1-producing plasmid Eco-N-1-p), J53-N2 (harboring a blaNDM-4-producing plasmid and a helper plasmid GX34p5), and J53-O (harboring a blaOXA-181-producing plasmid), could be stably inherited after 10 days of serial passage and no significant biological fitness costs were detected. Furthermore, we first reported the blaNDM-1 gene, derived from blaNDM-4 mutation (460C>A) under meropenem pressure, could be in vitro transferred into a self-conjugative, recombined plasmid Eco-N-1-p of J53-N1. Eco-N-1-p was mainly recombined by GX34p4_OXA-181 (40,449 bp, 75.16%) and GX34p1_NDM-4 (8,553 bp, 15.89%), in which IS26 and IS5-like probably played a major role. Eco-N-1-p could be transferred into the conjugation recipient K. pneumoniae KP54 and make the latter sacrifice fitness. The retention rates of blaNDM-1 remained high stability (>80% after 200 generations). The comparative genomic analysis of GX34 and those carrying blaNDM-4 or blaOXA-181 genes retrieved from the NCBI RefSeq database showed all blaNDM-4 (26/26, 100.00%) and blaOXA-181 (13/13, 100.00%) were surrounded by IS26. The immediate environment of blaNDM-4 and blaOXA-181 in GX34 and some retrieved strains shared identical features, hinting at their possible dissemination. Effective measures should be taken to monitor the spread of this clone.

In vitro activity of cefiderocol, a siderophore cephalosporin, against carbapenem-resistant hypervirulent Klebsiella pneumoniae in China.

Cefiderocol is a siderophore cephalosporin that binds ferric iron and utilizes iron transporters to cross the cell membrane. Hypervirulent Klebsiella pneumoniae (hvKp) is known to produce more siderophores; in this case, the uptake of cefiderocol may be decreased. Therefore, the objective of this study was to evaluate the in vitro activity of cefiderocol against hvKp isolates. A total of 320 carbapenem-resistant K. pneumoniae (CRKp) isolates were collected in China between 2014 and 2022, including 171 carbapenem-resistant hvKp (CR-hvKp) and 149 carbapenem-resistant classical K. pneumoniae (CR-cKp). Quantitative detection of siderophores showed that the average siderophore production of CR-hvKp (234.6 mg/L) was significantly higher than that of CR-cKp (68.9 mg/L, P < 0.001). The overall cefiderocol resistance rate of CR-hvKp and CR-cKp was 5.8% (10/171) and 2.7% (4/149), respectively. The non-susceptible rates of both cefiderocol and siderophore production of CR-hvKp isolates were higher than those of CR-cKp in either NDM-1- or KPC-2-producing groups. The MIC90 and MIC50 for CR-hvKp and CR-cKp were 8 mg/L and 2 mg/L and 4 mg/L and 1 mg/L, respectively. The cumulative cefiderocol MIC distribution for CR-hvKp was significantly lower than that of CR-cKp isolates (P = 0.003). KL64 and KL47 consisted of 53.9% (83/154) and 75.7% (53/70) of the ST11 CR-hvKp and CR-cKp, respectively, and the former had significantly higher siderophore production. In summary, cefiderocol might be less effective against CR-hvKp compared with CR-cKp isolates, highlighting the need for caution regarding the prevalence of cefiderocol-resistant K. pneumoniae strains, particularly in CR-hvKp isolates.

DeePMD-kit v2: A software package for deep potential models.

DeePMD-kit is a powerful open-source software package that facilitates molecular dynamics simulations using machine learning potentials known as Deep Potential (DP) models. This package, which was released in 2017, has been widely used in the fields of physics, chemistry, biology, and material science for studying atomistic systems. The current version of DeePMD-kit offers numerous advanced features, such as DeepPot-SE, attention-based and hybrid descriptors, the ability to fit tensile properties, type embedding, model deviation, DP-range correction, DP long range, graphics processing unit support for customized operators, model compression, non-von Neumann molecular dynamics, and improved usability, including documentation, compiled binary packages, graphical user interfaces, and application programming interfaces. This article presents an overview of the current major version of the DeePMD-kit package, highlighting its features and technical details. Additionally, this article presents a comprehensive procedure for conducting molecular dynamics as a representative application, benchmarks the accuracy and efficiency of different models, and discusses ongoing developments.

Laparoscopic placement of left renal vein extravascular stenting in treatment of nutcracker syndrome: Techniques and long-term outcomes.

OBJECTIVES: We aimed to assess the feasibility and efficacy of laparoscopic extravascular stent in treatment of nutcracker syndrome by transperitoneal or retroperitoneal approach. METHODS: Seventy-six patients with nutcracker syndrome were retrospectively enrolled from a tertiary referral center, and underwent transperitoneal (63 patients) or retroperitoneal (13 patients) laparoscopic extravascular stent from March 2011 to December 2020. Surgical parameters, complications, imaging and clinical outcomes were collected and analyzed. RESULTS: All procedures were successfully carried out without open conversion. The median operation time, estimated blood loss, and postoperative hospital day were 120 (interquartile range [IQR]: 90-144) min, 20 (IQR: 10-30) ml, and 7 (IQR: 6-9) days. At a median follow-up of 52 (range: 9-127) months, 60 (79%) patients had complete symptom resolution, 14 (18%) patients had significant symptom improvement, and 2 (3%) patients reported no symptom improvement. Ninety-four percent (50/53) of hematuria, 91% (30/33) of proteinuria, and 89% (25/28) of flank/abdominal pain resolved after extravascular LRV stenting. No significant differences were detected in surgery parameters and recovery rates of clinical symptoms between two approaches (each p > 0.05). However, patients with transperitoneal approach need longer to achieve complete recovery compared with retroperitoneal approach (8.7 vs. 1.5 months, p = 0.016). CONCLUSIONS: Laparoscopic extravascular stent performed either transperitoneally or retroperitoneally is a feasible and effective option in treatment of nutcracker syndrome. Retroperitoneal laparoscopic extravascular stent required shorter time to achieve complete recovery, which should be considered whenever possible in surgical decision-making.

Establishment and validation of an ultrasound-based nomogram with risk stratification for short disease-free survival in breast cancer.

PURPOSE: This retrospective study aimed to develop and validate an Ultrasound (US)-based nomogram to predict short disease-free survival (short-DFS, less than 120 months DFS) in breast cancer (BC). METHODS: Nomogram was established based on a training data of 311 BC patients by multivariable logistic regression, and were assessed by discrimination, calibration, and clinical usefulness. Risk stratification was performed by X-tile. An independent testing data of 200 patients with BC was used for external validation. RESULTS: Nine predictors including three US features and six clinical parameters were screened into the nomogram by Lasso (log λ = -3.594) in training data. Better performance was obtained in the training data (C-index: 0.942) and testing data (C-index: 0.914). Calibration analysis indicated optimal agreement between nomogram predictions and actual observations (p = 0.67). Decision curve analysis showed a great clinical benefit (Youden index: 0.634). Three risk levels are low-risk (<184.0), moderate-risk (184.0-345.3) and high-risk (>345.3). Our nomograms had larger area under the receiver operating characteristic (ROC) curves compared with Magee Equation and Nottingham Prognostic models (0.942 vs. 0.824, 0.790). CONCLUSION: The US-based nomogram and the practical score system facilitate individualized prediction of short-DFS to optimize clinical decisions and improve prognosis in patients with BC.

Sodium Bicarbonate Nanoparticles for Amplified Cancer Immunotherapy by Inducing Pyroptosis and Regulating Lactic Acid Metabolism.

Although immunotherapy has a broad clinical application prospect, it is still hindered by low immune responses and immunosuppressive tumor microenvironment. Herein, a simple and drug-free inorganic nanomaterial, alkalescent sodium bicarbonate nanoparticles (NaHCO3 NPs), is prepared via a fast microemulsion method for amplified cancer immunotherapy. The obtained alkalescent NaHCO3 regulates lactic acid metabolism through acid-base neutralization so as to reverse the mildly acidic immunosuppressive tumor environment. Additionally, it can further release high amounts of Na+ ions inside tumor cells and induce a surge in intracellular osmolarity, and thus activate the pyroptosis pathway and immunogenic cell death (ICD), release damage-associated molecular patterns (DAMPs) and inflammatory factors, and improve immune responses. Collectively, NaHCO3 NPs observably inhibit primary/distal tumor growth and tumor metastasis through acid neutralization remitted immunosuppression and pyroptosis induced immune activation, showing an enhanced antitumor immunity efficiency. This work provides a new paradigm for lactic acid metabolism and pyroptosis mediated tumor treatment, which has a potential for application in clinical tumor immunotherapy.

Two-dimensional speckle tracking echocardiography help identify breast cancer therapeutics-related cardiac dysfunction.

BACKGROUND: Cancer therapeutics-related cardiac dysfunction (CTRCD) from different chemotherapy strategies are underdetermined by echocardiography. As an imaging marker of subclinical cardiac dysfunction, two-dimensional speckle tracking echocardiography (2D-STE) may assist in identifying the impact patterns of different CTRCD. METHODS: A total of 67 consecutive patients with invasive ductal breast carcinoma who will undertake neoadjuvant chemotherapy were enrolled and grouped according to their different chemotherapy regimens based on their biopsy results. Group A included 34 patients who received anthracycline without trastuzumab, whereas Group B had 33 patients who received trastuzumab without anthracycline. Echocardiography was performed at three time-points, i.e., baseline (T0), cycle-2 (T2), and cycle-4 (T4) of chemotherapy. Conventional echocardiographic measurements and 2D-STE strain values, and myocardial work (MW) parameters, were compared between different groups at different time-points. RESULTS: The mean age had no statistical difference between the two groups. E/e' was the only conventional echocardiographic parameter that had variation in group A (P < 0.05). Compared with baseline, GLS in group A decreased at T2, and GCS decreased at T4 (P < 0.05). GLS and GCS in group B both decreased at T4 (P < 0.05). More patients in group A had a more than 15% fall of baseline GLS rather than GCS at T2 (P < 0.05), however, there was no difference of either GLS or GCS decline rate at T4 between the two groups. All the MW parameters in group A had variations overtime, whereas only GCW in group B (P < 0.05). CONCLUSION: Early subclinical myocardial dysfunction can be identified by 2D-STE in breast cancer patients with chemotherapy, and GLS provides profound value in demonstrating the temporal changes in early myocardial damage induced by anthracycline. LV contractility injury in patients with trastuzumab may be mild at first but increases in severity with exposure time as early as cycle-4. Awareness of these differences may help to stratify the prevention of late cardiovascular events caused by different CTRCDs. In addition, GCW may be the most sensitive myocardial work parameter of CTRCD.

Two-dimensional speckle tracking echocardiography in assessing the subclinical myocardial dysfunction in patients with gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) may increase the risk of cardiovascular disease and accompany asymptomatic deterioration of the myocardial function. This study aims to identify the subclinical impact of GDM on maternal left ventricular function by two-dimensional speckle tracking echocardiography (2D-STE). METHODS: We prospectively recruited 47 women with GDM and 62 healthy pregnant women who underwent transthoracic echocardiography (TTE) at 24 to 28 weeks of pregnancy. GDM diagnosis agreed with the IADPSG criteria. TTE was performed according to the criteria of the American Society of Echocardiography. Conventional echocardiographic data and 2D-STE parameters were compared between the two groups. RESULTS: Age, gestational weeks, heart rate, and conventional echocardiographic parameters had no difference between the two groups. The average LV global longitudinal strain (LV-GLS) of GDM patients was lower than controls (18.14 ± 2.53 vs. 22.36 ± 6.33, p < 0.001), and 31 patients (66%) in our study had an absolute LV-GLS less than 20%. The LA reservoir and conduit strain in patients with GDM were also significantly reduced (32.71 ± 6.64 vs. 38.00 ± 7.06, 20.41 ± 5.69 vs. 25.56 ± 5.73, p < 0.001). However, there was no significant difference in LA contractile function between the two groups. In multiple regression analysis, LV-GLS and LA conduit strain independently associated with GDM. CONCLUSIONS: 2D-STE could detect the subclinical myocardial dysfunction more sensitively than conventional echocardiography, with LV-GLS and LA conduit strain as independent indicators of the GDM impact on maternal cardiac function during pregnancy.

Assessing Whether Morphological Changes in Axillary Lymph Node Have Already Occurred Prior to Metastasis in Breast Cancer Patients by Ultrasound.

Background and Objectives: Whether the morphological changes in axillary lymph node (ALN) have occurred prior to metastasis remains unclear in breast cancer (BC) patients. The aim of this study is to investigate the influence of BC for the morphology of non-metastasis ALN (N−) and, further, to improve the performance of ultrasound (US) examination for metastasis ALN (N+). Materials and Methods: In this retrospective study, 653 patients with breast mass were enrolled and divided into normal group of 202 patients with benign breast tumor, N− group of 233 BC patients with negative ALN and N+ group of 218 BC patients with positive ALN. US features of ALN were evaluated and analyzed according to long (L) and short (S) diameter, the (L/S) axis ratio, cortical thickness, lymph node edge, replaced hilum and color Doppler flow imaging (CDFI). Results: ALN US features of short diameter, replaced hilum, cortical thickness and CDFI have significant statistical differences in N− group comparing with normal group and N+ group, respectively (p < 0.05). Conclusions: Therefore, BC can affect ALN and lead to US morphological changes whether lymph node metastasis is present, which reduces the sensitivity of axillary US. The combination of US and other examination methods should be applied to improve the diagnostic performance of N+.

Association between VEGF single nucleotide polymorphism and breast cancer in the Northern China Han population.

PURPOSE: To investigate the associations of four commonly studied single nucleotide polymorphisms (SNP) of the vascular endothelial growth factor (VEGF), including -460T/C (rs833061), - 634G/C (rs2010963), - 2578C/A (rs699947), and +936T/C (rs3025039), with the incidence, aggressiveness, and tumor markers expression of breast cancer in the Northern China Han population. METHODS: Followed the genomic DNA extraction, a total of 259 patients with breast cancer (case group) and 273 healthy women (control group) underwent genotyping by PCR-LDR SNP assays. The associations between VEGF gene polymorphisms and the incidence, aggressiveness, and tumor markers expression of breast cancer were analyzed. RESULTS: Significant differences were observed in allele frequency and genotype distribution of - 634G/C between breast cancer cases and healthy controls (p = 0.006, 0.013). Individuals who carry the G allele more likely had a lower risk of breast cancer (OR, 0.866, 95% CI 0.782-0.959). Compared with CC genotype carriers, women who had the CG and GG genotypes demonstrated a relatively lower risk (OR, 0.860, 95% CI 0.757-0.978, p = 0.022; OR, 0.778, 95% CI, 0.656-0.924, p = 0.004, respectively). When we stratified the group of patients according to the status of tumor markers, a significant association of - 634G/C SNP and Ki-67 expression was observed. The CC genotype carriers were more likely to be characterized by high expression of Ki-67 (p = 0.031). Further analysis showed that the - 460T/-634C/-2578C/+936C haplotype was more associated with a higher risk of breast cancer (OR, 1.445, 95% CI 1.123-1.859, p = 0.004), whereas the - 460T/- 634G/- 2578C/+936C one was associated with a lower risk (OR, 0.736, 95% CI 0.563-0.963, p = 0.025). CONCLUSIONS: In the present study, we concluded that VEGF gene - 634G/C polymorphism is related to the incidence of breast cancer in the Han population in Northern China and also might be associated with tumor proliferation index Ki-67.

Transcriptome sequencing reveals terpene biosynthesis pathway genes accounting for volatile terpene of tree peony.

MAIN CONCLUSION: Transcriptomic and volatile component analyses showed that high expression levels of genes from the terpenoid backbone biosynthesis pathway and the monoterpene metabolic pathway can strengthen the floral fragrance of tree peony. Floral fragrance is a crucial ornamental trait whose improvement is one of the primary objectives of tree peony breeding. So far, exploration of the floral fragrance of tree peony has focused on the identification of its volatile components, but the molecular mechanisms responsible for their formation remain unclear. Here, we identified 128 volatile components from the petals of tree peony and found that they consisted primarily of terpenes, alcohols, and esters. Based on the distribution pattern of these major fragrance components, 24 tree peony cultivars were classified into 4 types: grassy scent (ocimene), woody scent (longifolene), lily of the valley scent (linalool), and fruity scent (2-ethyl hexanol). We used RNA-seq to explore the mechanistic basis of terpenoid metabolism in tree peony petals with various scents. The expression levels of AACT, HMGR, PMK, DXS, DXR, HDS, HDR, and GGPS, which encode key enzymes of terpenoid backbone biosynthesis, were upregulated in 'Huangguan' (strong fragrance) compared to 'Fengdan' (faint fragrance). Moreover, the transcript abundance of LIS and MYS, two monoterpene synthase genes, was also enhanced in petals of 'Huangguan' compared to those of 'Fengdan'. Together, these results demonstrate that differences in the expression of genes from the monoterpene synthesis and terpenoid backbone pathways are associated with differences in the fragrance of tree peony. This research provides crucial genetic resources for fragrance improvement and also lays a foundation for further clarification of the mechanisms that underlie tree peony fragrance.

Higher titer hepatitis B core antibody predicts a higher risk of liver metastases and worse survival in patients with colorectal cancer.

BACKGROUND: There have been controversial voices on if hepatitis B virus infection decreases the risk of colorectal liver metastases or not. This study aims to the find the association between HBV infection and postoperative survival of colorectal cancer and the risk of liver metastases in colorectal cancer patients. METHODS: Patients who underwent curative surgical resection for colorectal cancer between January 2011 and December 2012 were included. Patients were grouped according to anti-HBc. Differences in overall survival, time to progress, and hepatic metastasis-free survival between groups and significant predictors were analyzed. RESULTS: Three hundred twenty-seven colorectal cancer patients were comprised of 202 anti-HBc negative cases and 125 anti-HBc positive cases, and anti-HBc positive cases were further divided into high-titer anti-HBc group (39) and low-titer anti-HBc group (86). The high-titer anti-HBc group had significantly worse overall survival (5-Yr, 65.45% vs. 80.06%; P < .001), time to progress (5-Yr, 44.26% vs. 84.73%; P < .001), and hepatic metastasis-free survival (5-Yr, 82.44% vs. 94.58%; P = .029) than the low-titer group. Multivariate model showed anti-HBc ≥ 8.8 S/CO was correlated with poor overall survival (HR, 3.510; 95% CI, 1.718-7.17; P < .001), time to progress (HR, 5.747; 95% CI, 2.789-11.842; P < .001), and hepatic metastasis-free survival (HR, 3.754; 95% CI, 1.054-13.369; P = .041) in the anti-HBc positive cases. CONCLUSIONS: Higher titer anti-HBc predicts a potential higher risk of liver metastases and a worse survival in anti-HBc positive colorectal cancer patients.

Semantic Segmentation Leveraging Simultaneous Depth Estimation.

Semantic segmentation is one of the most widely studied problems in computer vision communities, which makes a great contribution to a variety of applications. A lot of learning-based approaches, such as Convolutional Neural Network (CNN), have made a vast contribution to this problem. While rich context information of the input images can be learned from multi-scale receptive fields by convolutions with deep layers, traditional CNNs have great difficulty in learning the geometrical relationship and distribution of objects in the RGB image due to the lack of depth information, which may lead to an inferior segmentation quality. To solve this problem, we propose a method that improves segmentation quality with depth estimation on RGB images. Specifically, we estimate depth information on RGB images via a depth estimation network, and then feed the depth map into the CNN which is able to guide the semantic segmentation. Furthermore, in order to parse the depth map and RGB images simultaneously, we construct a multi-branch encoder-decoder network and fuse the RGB and depth features step by step. Extensive experimental evaluation on four baseline networks demonstrates that our proposed method can enhance the segmentation quality considerably and obtain better performance compared to other segmentation networks.

Ultrasound characteristics of sclerosing adenosis mimicking breast carcinoma.

BACKGROUND: Sclerosing adenosis (SA) is a benign lesion with complicated pathological components and could mimic breast carcinoma in both clinical palpation and medical imaging findings. The present study was conducted to assess the value of ultrasound (US) characteristics in diagnosing SA and their differentiation from breast carcinoma. METHODS: We retrospectively reviewed the medical records of 305 women (347 lesions) with invasive ductal carcinoma (IDC) and 54 women with single SA lesion, who had breast excision between April 2016 and July 2018. US BI-RADS atlas and elastography were applied and their associated characteristics were compared between SA and IDC. RESULTS: The mean age of SA was younger than that of IDC (43.6 ± 7.4 vs 53.2 ± 10.3, P < 0.001). Compared to IDC, SA had more frequency of parallel orientation (94.44% vs 71.76%, P < 0.001) and circumscribed margin (48.15% vs 4.90%, P < 0.001), less frequency of irregular shape (64.81% vs 95.97%, P < 0.001), hypoechoic echotexture (88.89% vs 98.27%, P = 0.002), calcification (12.96% vs 55.04%, P < 0.001), and posterior acoustic changes (3.70% vs 53.89%, P < 0.001) or associated features (architectural distortion, 3.70% vs 59.65%, P < 0.001; duct changes, 18.52% vs 63.40%, P < 0.001). Vascularity absence was more common in SA compared to IDC (35.19% vs 6.63%, P < 0.001). And the elasticity score was lower in SA (2.38 ± 0.60 vs 3.91 ± 0.81, P < 0.001). After adjusting for age, we found spiculated margin, posterior shadowing, calcification, architectural distortion, and vascularity could independently identify the differences between these two entities. After involving elasticity score, the calcification and vascularity could still be independent indicators for differential diagnosis. CONCLUSION: Understanding SA imaging features will enable radiologists to communicate results to the referring physician consistently, which could benefit a reliable assessment and specific management recommendations. A systematic evaluation of the US BI-RADS atlas together with breast elastography may be a powerful tool to identify SA and differentiate it from breast cancer.

Heterogeneity of Triple-Negative Breast Cancer: Differences in Clinicopathologic and Ultrasound Features Between Premenopausal and Postmenopausal Patients.

OBJECTIVES: The aim of this study was to determine whether any salient differences exist in triple-negative breast cancer (TNBC) between premenopausal and postmenopausal patients by comprehensively comparing the ultrasound (US) and clinicopathologic features of these patients. METHODS: A detailed evaluation of the US and clinicopathologic features of 60 tumors from 60 patients with a diagnosis of TNBC (36 premenopausal and 24 postmenopausal women) was conducted in this retrospective study. RESULTS: Triple-negative breast cancer in premenopausal patients was more likely to show a round or oval shape and microlobulated margins, more commonly exerted effects on surrounding tissue, and showed grade 3 blood flow according to the method of Adler et al (Ultrasound Med Biol 1990; 16:553-559) compared with tumors in postmenopausal women. Triple-negative breast cancer in postmenopausal patients showed some similar US features as those observed in estrogen receptor-positive tumors, including irregular shapes, angular or spiculated margins, and nonparallel growth to the skin (P < .05 for all). CONCLUSIONS: Although US cannot be used to unequivocally identify TNBC, it can distinguish some salient US features regarding TNBC between premenopausal and postmenopausal women. Such information can then provide some valuable predictive information on the diagnosis of TNBC for clinicians.