Molecular imaging reveals the heterogeneous progression of tumor cells and tumor stroma: a practice of FDG PET and FAPI PET in diagnosing PSMA-negative bone metastases of progressive prostate cancer.

Tumors are often with complex and heterogeneous biological processes, such as glycometabolism and fibrosis, which are the main biochemical pathways that determine therapeutic effects. Specifically, this study aims to assess the diagnosing performance of 18F-FDG and 68Ga-FAPI-04 PET for different stages of progressive bone metastases with PSMA-negative pathology. Bone metastatic mouse model of prostate cancer was constructed via intra-bone injection of PSMA-negative prostate cancer PC3 cells. Cellular uptakes of 18F-FDG and 68Ga-FAPI-04 were separately performed on PC3, NIH-3T3 (FAP-positive) and a mixture. 68Ga-PSMA-11, 18F-FDG and 68Ga-FAPI-04 PET/CT imaging were performed at 2, 4 weeks after tumor cell transplantation. Furthermore, PSMA and FAP expression in bone metastases were assessed by immunohistochemistry, and then compared with the imageological findings. On the cellular level, the independent tracer uptake on the basis of glycometabolism and fibrosis was observed. For animal imaging, 68Ga-PSMA-11 imaging showed weak or absent tracer uptake in PSMA-negative bone metastatic lesions. In contrast, 68Ga-FAPI-04 PET of bone metastases had a higher uptake and tumor-to-muscle (T/M) ratio than 18F-FDG PET that was relative steady during the observation, but T/M ratio of fibrosis gradually decreased with increasing tumor growth, which ranged from 5.11 ± 1.26 at 2 weeks to 3.54 ± 0.23 at 4 weeks, revealing the delayed formation of tumor stroma in rapid proliferation. In addition, PET imaging results were corroborated by immunohistochemical assessment. In conclusion, molecular imaging approach revealed the heterogeneous progression of tumor cells and tumor stroma of bone metastasis of prostate cancer, and further confirming the necessity of multi-molecular imaging in cancer imaging.

Pharmacodynamic material basis and pharmacological mechanisms of Cortex Mori against diabetes mellitus.

ETHNOPHARMACOLOGICAL RELEVANCE: The application of Cortex Mori (CM) in the treatment of diabetes mellitus (DM) has been extensively documented in traditional medicine. In recent years, the chemical composition of CM has been gradually unraveled, and its therapeutic mechanism in treating DM, diabetic nephropathy, diabetic cardiomyopathy, and other related conditions has been highlighted in successive reports. However, there is no systematic study on the treatment of DM based on the chemical composition of CM. AIM OF THE STUDY: This study was conducted to systematically explore the hypoglycemic activity mechanism of CM based on its chemical composition. METHODS: The material basis of Cortex Mori extract (CME) was investigated through qualitative analyses based on liquid chromatography-mass spectrometry (LC-MS). The possible acting mechanism was simulated using network pharmacology and validated in streptozotocin (STZ) + high fat diet (HFD)-induced diabetic rats and glucosamine-induced IR-HepG2 model with the assistance of molecular docking techniques. RESULTS: A total of 39 compounds were identified in CME by the LC-MS-based qualitative analysis. In diabetic rats, it was demonstrated that CME significantly ameliorated insulin resistance, blood lipid levels, and liver injury. The network pharmacology analysis predicted five major targets, including AKT1, PI3K, FoxO1, Gsk-3ß, and PPARγ. Additionally, three key compounds (resveratrol, protocatechuic acid, and kaempferol) were selected based on their predicted contributions. The experimental results revealed that CME, resveratrol, protocatechuic acid, and kaempferol could promote the expression of AKT1, PI3K, and PPARγ, while inhibiting the expression of FoxO1 and Gsk-3ß. The molecular docking results indicated a strong binding affinity between resveratrol/kaempferol and their respective targets. CONCLUSIONS: CME contains a substantial amount of prenylated flavonoids, which may be the focal point of research on the efficacy of CM in the treatment of DM. Besides, CME is effective in controlling blood glucose and insulin resistance, improving lipid levels, and mitigating liver injury in patients with DM. Relevant mechanisms may be associated with the activation of the PI3K/Akt pathway, the inhibition of the expression of FoxO1 and Gsk-3ß, and the enhancement of PPARγ activity. This study represents the first report on the role of CME in the treatment of DM through regulating PPARγ, FoxO1, and Gsk-3ß.

Rational construction of visible-light-driven perylene diimides/Fe2O3@C derived from MIL-88A (Fe) heterojunction with S-scheme electron transfer pathway to activate peroxymonosulfate for degradation of antibiotics.

The novel composite photocatalytic material perylene diimides/Fe2O3@C (PDIs/Fe2O3@C) was constructed by a simple hydrothermal-calcination method and an oil bath method. 20 % PDIs/Fe2O3@C displayed a 16.4-fold increase in the rate of tetracycline (TC) removal over Fe2O3@C at 8 min. The main factor that enhanced photocatalytic performance was due to the combination of PDIs with Fe2O3@C, which effectively improved the phenomenon during the self-assembly of highly agglomerative PDIs, increased the specific surface area of Fe2O3@C, exposed more reaction sites, and promoted the activation of peroxymonosulfate (PMS) by Fe2+/Fe3+; and secondly, the composite of two different materials, both organic and inorganic, which effectively promoted the photogenerated electron transfer and the separation of electron-hole pairs, the a new S-scheme electron transport pathway is formed, which effectively promoted the photogenerated electron transfer as well as the e--h+ separation, which was more favorable for the activation of PMS. The whole reaction pathway and product toxicity were thoroughly evaluated by Fukui function calculations, Liquid Chromatograph Mass Spectrometer (LC-MS), and Toxicity Estimation Software Tool (T.E.S.T.) simulation results, which demonstrated the rationality of the degradation pathway and the greatly reduced product toxicity. Moreover, the composites were effective and versatile for all other antibiotics (chlortetracycline (CTC), ciprofloxacin (CIP) and sulfadiazine (SDZ)). As an advanced oxidation process, the activation of PDIs/Fe2O3@C under visible light shows its potential application in pollutant degradation, which provides new perspectives and ideas for further effective treatment of real wastewater.

Thyroid Nodules: Emerging Trends in Detection and Visualization based on Citespace.

BACKGROUND: Thyroid nodule (TN) is a highly prevalent clinical endocrine disease. Many countries have formed guidelines on the prevention and treatment of TN based on extensive research. However, there is a scarcity of TN-related literature based on bibliometrics. OBJECTIVES: This study aimed to evaluate the scientific achievements and progress of TN research from a global perspective by investigating the literature for 20 years through bibliometrics. METHODS: We searched the literature on TN in the core collection of the Web of Science database from 2002 to 2021 and used the Citespace software to analyze the co-authorship, co-citation, and co-occurrence of countries, institutions, authors, keywords, and co-cited literature. RESULTS: We retrieved 12319 documents related to TN. The literature on TN has been growing since 2002. The United States has contributed the largest proportion of TN papers (20.64%), followed by China, Italy, and South Korea. The United States ranked first in terms of centrality (0.38). Haugen BR, Gharib H, and Cibas ES are the top three most cited authors. The papers published in Thyroid were cited most frequently (7952 times). The most prominent keywords were management, cancer, fine needle aspiration, diagnosis, malignant tumor, thyroid cancer, ultrasound, biopsy, benign, surgery, ablation, and cytology. All keywords could be divided into three categories: diagnosis stratification, treatment, and cancer. As far as potential hot spots are concerned, the keywords that have recently burst strongly and are still continuing are: "Association Guideline" (2018-2021), "Radiofrequency Ablation" (2017-2021), "Classification" (2019-2021), and "Data System" (2017-2021). CONCLUSION: Based on the current trends, the number of publications on TN will continue to increase. The United States is the most active contributor to research in this field. Previous literature focused on stratification, cancer, surgery, and ablation, and there were different opinions on the stratification of diagnosis. There were relatively few studies on pathogenesis and treatment using medicine. More focus will be placed on association guidelines, radiofrequency ablation, classification, and data system, which may be the next popular topics in TN research.

Effect of α-methyl on the performance of photocurable 3D printing polyurethane materials.

For photosensitive polyurethane systems, reactive diluents are indispensable components whose main role is to reduce the viscosity of the polyurethane prepolymer to meet the requirements of the photocurable 3D printing technology for high fluidity of the precursor solution. Generally, the reactive diluent would be involved in the photocuring reaction, which in turn has a remarkable impact on the mechanical, reaction kinetics, and thermodynamic characteristics of the photosensitive polyurethane system. However, this feature is usually neglected in the study of photosensitive urethane acrylate (PUA) systems, so there is a considerable necessity to investigate the mechanism of active diluents in the photocured reaction of PUA systems. In this work, the effects of α-methyl groups along the chains of diluent molecules on the photoreaction kinetics, photocurable 3D printing, mechanical and mechanical properties, and thermodynamic characteristics of PUAs were investigated employing hydroxyethyl methacrylate and hydroxyethyl acrylate as active diluents, respectively. The relationship between chemical structure and kinetics of PUA systems was also elucidated by using dynamic mechanical analysis tests. The results demonstrated that the α-methyl group blocks the migration of reactive radicals, reduces the efficiency of the photoreaction, and causes an increase in the rigidity and strength of the molecular chain. This study not only revealed the effect of α-methyl on the kinetic mechanical and thermal performance of PUA systems but also paves the way for the development of a new class of photosensitive PUA materials used for the photocurable 3D printing technology.

Effect of grape pomace supplement on growth performance, gastrointestinal microbiota, and methane production in Tan lambs.

Grape pomace (GP), a by-product in wine production, is nutritious and can be used as a feed ingredient for ruminants; however, its role in shaping sheep gastrointestinal tract (GIT) microbiota is unclear. We conducted a controlled trial using a randomized block design with 10 Tan lambs fed a control diet (CD) and 10 Tan lambs fed a pelleted diet containing 8% GP (dry matter basis) for 46 days. Rumen, jejunum, cecum, and colon bacterial and archaeal composition were identified by 16S rRNA gene sequencing. Dry matter intake (DMI) was greater (p < 0.05) in the GP than CD group; however, there was no difference in average daily gain (ADG, p < 0.05) and feed conversion ratio (FCR, p < 0.05) between the two groups. The GP group had a greater abundance of Prevotella 1 and Prevotella 7 in the rumen; of Sharpe, Ruminococcaceae 2, and [Ruminococcus] gauvreauii group in the jejunum; of Ruminococcaceae UCG-014 and Romboutsia in the cecum, and Prevotella UCG-001 in the colon; but lesser Rikenellaceae RC9 gut group in the rumen and cecum, and Ruminococcaceae UCG-005 and Ruminococcaceae UCG-010 in the colon than the CD group. The pathways of carbohydrate metabolism, such as L-rhamnose degradation in the rumen, starch and glycogen degradation in the jejunum, galactose degradation in the cecum, and mixed acid fermentation and mannan degradation in the colon were up-graded; whereas, the pathways of tricarboxylic acid (TCA) cycle VIII, and pyruvate fermentation to acetone in the rumen and colon were down-graded with GP. The archaeal incomplete reductive TCA cycle was enriched in the rumen, jejunum, and colon; whereas, the methanogenesis from H2 and CO2, the cofactors of methanogenesis, including coenzyme M, coenzyme B, and factor 420 biosynthesis were decreased in the colon. The study concluded that a diet including GP at 8% DM did not affect ADG or FCR in Tan lambs. However, there were some potential benefits, such as enhancing propionate production by microbiota and pathways in the GIT, promoting B-vitamin production in the rumen, facilitating starch degradation and amino acid biosynthesis in the jejunum, and reducing methanogenesis in the colon.

Evaluating the clinical utility of speech analysis and machine learning in schizophrenia: A pilot study.

BACKGROUND: Schizophrenia is a serious mental disorder that significantly impacts social functioning and quality of life. However, current diagnostic methods lack objective biomarker support. While some studies have indicated differences in audio features between patients with schizophrenia and healthy controls, these findings are influenced by demographic information and variations in experimental paradigms. Therefore, it is crucial to explore stable and reliable audio biomarkers for an auxiliary diagnosis and disease severity prediction of schizophrenia. METHOD: A total of 130 individuals (65 patients with schizophrenia and 65 healthy controls) read three fixed texts containing positive, neutral, and negative emotions, and recorded them. All audio signals were preprocessed and acoustic features were extracted by a librosa-0.9.2 toolkit. Independent sample t-tests were performed on two sets of acoustic features, and Pearson correlation on the acoustic features and Positive and Negative Syndrome Scale (PANSS) scores of the schizophrenia group. Classification algorithms in scikit-learn were used to diagnose schizophrenia and predict the level of negative symptoms. RESULTS: Significant differences were observed between the two groups in the mfcc_8, mfcc_11, and mfcc_33 of mel-frequency cepstral coefficient (MFCC). Furthermore, a significant correlation was found between mfcc_7 and the negative PANSS scores. Through acoustic features, we could not only differentiate patients with schizophrenia from healthy controls with an accuracy of 0.815 but also predict the grade of the negative symptoms in schizophrenia with an average accuracy of 0.691. CONCLUSIONS: The results demonstrated the considerable potential of acoustic characteristics as reliable biomarkers for diagnosing schizophrenia and predicting clinical symptoms.

ETCM v2.0: An update with comprehensive resource and rich annotations for traditional Chinese medicine.

Existing traditional Chinese medicine (TCM)-related databases are still insufficient in data standardization, integrity and precision, and need to be updated urgently. Herein, an Encyclopedia of Traditional Chinese Medicine version 2.0 (ETCM v2.0, http://www.tcmip.cn/ETCM2/front/#/) was constructed as the latest curated database hosting 48,442 TCM formulas recorded by ancient Chinese medical books, 9872 Chinese patent drugs, 2079 Chinese medicinal materials and 38,298 ingredients. To facilitate the mechanistic research and new drug discovery, we improved the target identification method based on a two-dimensional ligand similarity search module, which provides the confirmed and/or potential targets of each ingredient, as well as their binding activities. Importantly, five TCM formulas/Chinese patent drugs/herbs/ingredients with the highest Jaccard similarity scores to the submitted drugs are offered in ETCM v2.0, which may be of significance to identify prescriptions/herbs/ingredients with similar clinical efficacy, to summarize the rules of prescription use, and to find alternative drugs for endangered Chinese medicinal materials. Moreover, ETCM v2.0 provides an enhanced JavaScript-based network visualization tool for creating, modifying and exploring multi-scale biological networks. ETCM v2.0 may be a major data warehouse for the quality marker identification of TCMs, the TCM-derived drug discovery and repurposing, and the pharmacological mechanism investigation of TCMs against various human diseases.

A Nonlinear-Model-Based High-Bandwidth Current Sensor Design for Switching Current Measurement of Wide Bandgap Devices.

With the growing adoption of wide bandgap devices in power electronic applications, current sensor design for switching current measurement has become more important. The demands for high accuracy, high bandwidth, low cost, compact size, and galvanic isolation pose significant design challenges. The conventional modeling approach for bandwidth analysis of current transformer sensors assumes that the magnetizing inductance remains constant, which does not always hold true in high-frequency operations. This can result in inaccurate bandwidth estimation and affect the overall performance of the current sensor. To address this limitation, this paper provides a comprehensive analysis of nonlinear modeling and bandwidth, considering the varying magnetizing inductance in a wide frequency range. A precise and straightforward arctangent-based fitting algorithm was proposed to accurately emulate the nonlinear feature, and the fitting results were compared with the magnetic core's datasheet to confirm its accuracy. This approach contributes to more accurate bandwidth prediction in field applications. In addition, the droop phenomenon of the current transformer and saturation effects are analyzed in detail. For high-voltage applications, different insulation methods are compared and an optimized insulation process is proposed. Finally, the design process is experimentally validated. The bandwidth of the proposed current transformer is around 100 MHz and the cost is around $20, making it a low-cost and high-bandwidth solution for switching current measurements in power electronic applications.

Effect of dietary Agriophyllum squarrosum on average daily gain, meat quality and muscle fatty acids in growing Tan lambs.

The herb A. squarrosum is reputed to possess medicinal properties for humans, and has the potential to be a feed resource for livestock. We hypothesized that this herb would improve the meat quality of lambs. To test this hypothesis, 24 Tan ewe-lambs (27.7 ± 0.45 kg) were offered diets containing 0 (CON), 100 (AS100), 200 (AS200) and 300 (AS300) g A. squarrosum/kg DM, and average daily gain, carcass traits, blood metabolites, meat quality and fatty acid profiles were determined. Drip loss % and cooking loss % decreased with the AS100 and AS200 diets (P < 0.05). Dietary A. squarrosum reduced muscle fiber area and diameter and increased density of the meat (P < 0.05), which indicated that the meat was more tender. The concentrations of C10:0 and C18:1n-9 t were 1ower and of C17:0 and C18:3n-3 were greater in the AS200 and AS300 treatments than CON (P < 0.05). Our results suggest that feeding lambs up to 200 g/kg DM of A. squarrosum can increase the water-holding capacity and L* value of meat without compromising growth. Further research is needed to determine the optimal level.

Gadoxetic acid-enhanced MRI with a focus on LI-RADS v2018 imaging features predicts the prognosis after radiofrequency ablation in small hepatocellular carcinoma.

Introduction: Gadoxetic acid-enhanced magnetic resonance imaging (MRI) contributes to evaluating the prognosis of small hepatocellular carcinoma (sHCC) following treatment. We have investigated the potential role of gadoxetic acid-enhanced MRI based on LI-RADS (Liver Imaging Reporting and Data System) v2018 imaging features in the prognosis prediction of patients with sHCC treated with radiofrequency ablation (RFA) as the first-line treatment and formulated a predictive nomogram. Methods: A total of 204 patients with sHCC who all received RFA as the first-line therapy were enrolled. All patients had undergone gadoxetic acid-enhanced MRI examinations before RFA. Uni- and multivariable analyses for RFS were assessing using a Cox proportional hazards model. A novel nomogram was further constructed for predicting RFS. The clinical capacity of the model was validated according to calibration curves, the concordance index (C-index), and decision curve analyses. Results: Alpha fetoprotein (AFP) > 100 ng/ml (HR, 2.006; 95% CI, 1.111-3.621; P = 0.021), rim arterial phase hyperenhancement (APHE) (HR, 2.751; 95% CI, 1.511-5.011; P = 0.001), and targetoid restriction on diffusion-weighted imaging (DWI) (HR, 3.289; 95% CI, 1.832-5.906; P < 0.001) were considered as the independent risk features for recurrence in patients with sHCC treated with RFA. The calibration curves and C-indexes (C-index values of 0.758 and 0.807) showed the superior predictive performance of the integrated nomogram in both the training and validation groups. Discussion: The gadoxetic acid-enhanced MRI features based on LI-RADS v2018, including rim APHE, targetoid restriction on DWI, and the AFP level, are the independent risk factors of recurrence in patients with sHCC treated with RFA as the first-line therapy. The predictive clinical-radiological nomogram model was constructed for clinicians to develop individualized treatment and surveillance strategies.

Ontology characterization, enrichment analysis, and similarity calculation-based evaluation of disease-syndrome-formula associations by applying SoFDA.

Clinical symptom-based diagnosis and therapy play a crucial role in personalized medicine and drug discovery. The syndromes, distinctive groups of clinical symptoms summarized by traditional Chinese medicine (TCM) theories and clinical experiences, are used as the core diagnostic criteria and therapeutic guidance in TCM. However, there is still a lack of standardized data, information, and intrinsic molecular basis to help TCM syndromes better classify diseases and guide tailored medications. To address this problem, we built the first integrated web platform, SoFDA (http://www.tcmip.cn/Syndrome/front/), with a curated ontology of 319 TCM syndromes, 8045 diseases, and 1359 TCM herbal formulas and their relationships with genes, diseases, and formulas. This platform proposed an association measurement by calculating Jaccard/Cosine similarities between TCM syndromes and their related biomedical entities with case and control validations. On this basis, the SoFDA platform enables biomedical and pharmaceutical scientists to rank and filter the most promising associations for disease diagnosis and tailored interventions. Conversely, the targeted gene sets and symptom sets can also be associated with TCM syndromes, formulas, and diseases for function illustration. Notably, SoFDA explores the multi-way associations among diseases, TCM syndromes, symptom genes, herbal formulas, drug targets, and pathways in heterogeneous biomedical networks with lots of customization. The protocol here implements all the analyses above using the SoFDA platform. Collectively, SoFDA may provide insights into the biological basis of disease-specific TCM syndromes and the underlying molecular mechanisms, as well as a tailored treatment for single or multiple symptoms within a syndrome.

Dietary Supplementation of Fruit from Nitraria tangutorum Improved Immunity and Abundance of Beneficial Ruminal Bacteria in Hu Sheep.

The fruit of Nitraria tangutorum (FNT) is reputed to possess medicinal properties; however, its effect on sheep (Ovis aries) is unknown. The aim of this study was to fill this gap. In a 3 × 3 Latin square design, six 12-month-old rumen-fistulated Hu rams (56.2 ± 8.26 kg; mean ± SD) were penned individually and offered one of three levels of FNT, namely, 0 g/d (control; CON), 16 g/d (N16), and 48 g/d (N48). The concentration of serum immunoglobulin G increased linearly (p = 0.03) with an increasing intake of FNT. The serum concentration of ß-hydroxybutyrate in the N48 group was lower than in the CON group (p = 0.01) and decreased linearly with increasing FNT (p = 0.001). The concentration of serum lactate dehydrogenase tended to decrease (p = 0.07) linearly with an increase in FNT intake, while the concentration of glucose did not differ among groups (p = 0.14) but displayed a quadratic curve with an increase in FNT (p = 0.05). The rumen concentration of lipase decreased linearly with increasing FNT (p = 0.04). The rumen fermentation variables were not affected by FNT. The FNT intake increased the abundance of beneficial ruminal bacteria, such as Lachnoclostridium, Rhodocyclaceae, and Candidatus Arthromitus. Prevotella, Rikenellaceae_RC9_gut_group, Ruminococcus, Olsenella, Lachnospiraceae_NK3A20_group, and Quinella were the dominant bacterial genera in all treatments. We conclude that FNT can improve immunity and increase the relative abundance of beneficial ruminal bacteria in sheep.

Theoretical study on the cross-linking reaction mechanism of cellulose nanofibrils initiated by fluorine.

Theoretical investigation on the cross-linking reaction process and mechanism of cellulose nanofibrils (CNFs) initiated by fluorine is accomplished by density functional theory. Three reaction pathways generated aldehyde and ester are identified. The reaction potential energy information of the ten reaction channels at B3LYP/6-311+G(d,p) level are obtained. The calculation results show that the reaction pathway of forming ester thereafter acyl fluoride has realized the cross-linking of cellulose. The reaction pathway of forming ester is more kinetically and thermodynamically favorable than the others of forming aldehyde with the lower energy barriers. The oxidation site mainly occurred at the methylene hydrogen of the hydroxymethyl group in the cellulose. The cross-linking of two cellulose molecules initiated by fluorine forming a covalent ester bond would be beneficial to improve cellulose mechanical properties of the insulating paper, which is better to add cellulose nanofibrils served as a "bridge" for strengthening the connection between celluloses.

Prevalence and diversity of small rodent-associated Bartonella species in Shangdang Basin, China.

The aim of this study was to investigate the occurrence and molecular characteristics of Bartonella infections in small rodents in the Shangdang Basin, China. Small rodents were captured using snap traps, and their liver, spleen, and kidney tissues were harvested for Bartonella detection and identification using a combination of real-time PCR of the ssrA gene (296 bp) and conventional PCR and sequencing of the gltA gene (379 bp). Results showed that 55 of 147 small rodents to be positive for Bartonella, with a positivity rate of 37.41%, and 95% confidence interval of 29.50%- 45.33%. While the positivity rate across genders (42.62% in males and 33.72% in females, χ2 = 1.208, P = 0.272) and tissues (28.57% in liver, 33.59% in spleen, and 36.76% in kidney, χ2 = 2.197, P = 0.333) of small rodents was not statistically different, that in different habitats (5.13% in villages, 84.44% in forests, and 54.17% in farmlands, χ2 = 80.105, P<0.001) was statistically different. There were 42 Bartonella sequences identified in six species, including 30 B. grahamii, three B. phoceensis, two B. japonica, two B. queenslandensis, one B. fuyuanensis and four unknown Bartonella species from Niviventer confucianus, Apodemus agrarius and Tscherskia triton. In addition to habitat, Bartonella species infection could be affected by the rodent species as well. Among the Bartonella species detected in this area, B. grahamii was the dominant epidemic species (accounting for 71.43%). B. grahamii exhibited four distinct clusters, and showed a certain host specificity. In addition, 11 haplotypes of B. grahamii were observed using DNASP 6.12.03, among which nine haplotypes were novel. Overall, high occurrence and genetic diversity of Bartonella were observed among small rodents in the Shangdang Basin; this information could potentially help the prevention and control of rodent-Bartonella species in this area.

Vandetanib drives growth arrest and promotes sensitivity to imatinib in chronic myeloid leukemia by targeting ephrin type-B receptor 4.

The oncogenic role of ephrin type-B receptor 4 (EPHB4) has been reported in many types of tumors, including chronic myeloid leukemia (CML). Here, we found that CML patients have a higher EPHB4 expression level than healthy subjects. EPHB4 knockdown inhibited growth of K562 cells (a human immortalized myelogenous leukemia cell line). In addition, transient transfection of EPHB4 siRNA led to sensitization to imatinib. These growth defects could be fully rescued by EPHB4 transfection. To identify an EPHB4-specific inhibitor with the potential of rapid translation into the clinic, a pool of clinical compounds was screened and vandetanib was found to be most sensitive to K562 cells, which express a high level of EPHB4. Vandetanib mainly acts on the intracellular tyrosine kinase domain and interacts stably with a hydrophobic pocket. Furthermore, vandetanib downregulated EPHB4 protein via the ubiquitin-proteasome pathway and inhibited PI3K/AKT and MAPK/ERK signaling pathways in K562 cells. Vandetanib alone significantly inhibited tumor growth in a K562 xenograft model. Furthermore, the combination of vandetanib and imatinib exhibited enhanced and synergistic growth inhibition against imatinib-resistant K562 cells in vitro and in vivo. These findings suggest that vandetanib drives growth arrest and overcomes the resistance to imatinib in CML via targeting EPHB4.

MRI Feature-Based Nomogram Model for Discrimination Between Non-Hypervascular Pancreatic Neuroendocrine Tumors and Pancreatic Ductal Adenocarcinomas.

This study aimed to investigate whether magnetic resonance imaging (MRI) features could differentiate non-hypervascular pancreatic neuroendocrine tumors (PNETs) from pancreatic ductal adenocarcinomas (PDACs). In this study, 131 patients with surgically and pathologically proven non-hypervascular PNETs (n = 44) or PDACs (n = 87) were enrolled. Two radiologists independently analyzed MRI imaging findings and clinical features. Relevant features in differentiating non-hypervascular PNETs from PDACs were identified via univariate and multivariate logistic regression models. The MRI feature-based nomogram was constructed based on multivariable logistic analysis and the reliability of the constructed nomogram was further validated. The results showed that tumor margin (P = 0.012; OR: 6.622; 95% CI: 1.510, 29.028), MPD dilation (P = 0.047; OR: 4.309; 95% CI: 1.019, 18.227), and signal in the portal phase (P < 0.001; OR: 53.486; 95% CI: 10.690, 267.618) were independent discriminative MRI features between non-hypervascular PNETs and PDACs. The discriminative performance of the developed nomogram was optimized compared with single imaging features. The calibration curve, C-index, and DCA validated the superior practicality and usefulness of the MRI-based nomogram. In conclusion, the radiologically discriminative model integrating various MRI features could be preoperatively and easily utilized to differentiate non-hypervascular PNETs from PDACs.

Fuzzy identification of bioactive components for different efficacies of rhubarb by the back propagation neural network association analysis of UPLC-Q-TOF/MSE and integrated effects.

BACKGROUND: Rhei Radix et Rhizoma (rhubarb), as one of the typical representatives of multi-effect traditional Chinese medicines (TCMs), has been utilized in the treatment of various diseases due to its multicomponent nature. However, there are few systematic investigations for the corresponding effect of individual components in rhubarb. Hence, we aimed to develop a novel strategy to fuzzily identify bioactive components for different efficacies of rhubarb by the back propagation (BP) neural network association analysis of ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry for every data (UPLC-Q-TOF/MSE) and integrated effects. METHODS: Through applying the fuzzy chemical identification, most components of rhubarb were classified into different chemical groups. Meanwhile the integration effect values of different efficacies can be determined by animal experiment evaluation and multi-attribute comprehensive indexes. Then the BP neural network was employed for association analysis of components and different efficacies by correlating the component contents determined from UPLC-Q-TOF/MSE profiling and the integration effect values. Finally, the effect contribution of one type of components may be totaled to demonstrate the universal and individual characters for different efficacies of rhubarb. RESULTS: It suggested that combined anthraquinones, flavanols and their polymers may be the universal character to the multi-functional properties of rhubarb. Other components contributed to the individuality of rhubarb efficacies, including stilbene glycosides, anthranones and their dimers, free anthraquinones, chromones, gallic acid and gallotannins, butyrylbenzenes and their glycosides. CONCLUSIONS: Our findings demonstrated that the bioactive components for different efficacies of rhubarb were not exactly the same and can be systematically differentiated by the network-oriented strategy. These efforts will advance our knowledge and understanding of the bioactive components in rhubarb and provide scientific evidence to support the expansion of its use in clinical applications and the further development of some products based on this medicinal herb.