Ameliorative Effects of Curcumin on Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM), a multifactorial and complicated metabolic disorder, is a growing public health problem. Numerous studies have indicated that bioactive compounds from herbal medicine have beneficial effects on T2DM prevention and treatment, owing to their numerous biological properties. Curcumin, the major curcuminoid of turmeric, is one of the most studied bioactive components of herbal supplements, and has a variety of biological activities. Clinical trials and preclinical research have recently produced compelling data to demonstrate the crucial functions of curcumin against T2DM via several routes. Accordingly, this review systematically summarizes the antidiabetic activity of curcumin, along with various mechanisms. Results showed that effectiveness of curcumin on T2DM is due to it being anti-inflammatory, anti-oxidant, antihyperglycemic, anti-apoptotic, and antihyperlipidemic, among other activities. In light of these results, curcumin may be a promising prevention/treatment choice for T2DM.

Efficient and systematic parameter extraction based on rate equations by DFB equivalent circuit model.

The conventional direct parameter extraction method generally suffers from cumbersome due to redundant experiments. An efficient and systematical parameter extracting solution is proposed based on an equivalent circuit model of distributed feedback (DFB) lasers. The successfully built circuit model includes the necessary intrinsic parameters in the rate equations and the extrinsic parameters to provide a better approximation of the actual laser. This method is experimentally verified through a DFB laser chip measurement of electronic and optical performance under the same conditions. Finally, the nine intrinsic parameters in the rate equations and five extrinsic parameters in the model are efficiently extracted using this technique from a set of experimental characteristics of a DFB laser chip. Modeled and measured results for the laser output characteristics exhibit good agreement when the extracted parameters are used. The method is versatile for other semiconductor lasers that can be modeled using rate equations. Comparison with simulation results of published laser models further validates the reliability of the presented model and extraction method.

Nonreciprocal Antisymmetric Magnetoresistance and Unconventional Hall Effect in a Two-Dimensional Ferromagnet.

Two-dimensional (2D) ferromagnets with high Curie temperatures provide a rich platform for exploring the exotic phenomena of 2D magnetism and the potential of spintronic devices. As a prototypical 2D ferromagnet, Fe5-xGeTe2 has recently been reported to possess a high Curie temperature with Tc ∼ 310 K, making it a promising candidate for advancing 2D nanoelectromechanical systems. However, due to its intricate magnetic ground state and magnetic domains, a thorough study of the transport behavior related to its lattice and domain structures is still lacking. Here, we report a nonreciprocal antisymmetric magnetoresistance in Fe5-xGeTe2 nanoflakes observed under an external magnetic field between 85-120 K. Through a detailed examination of its temperature, field orientation, and sample thickness dependence, we trace its origin to an additional electric field induced by the domain structure. This differs from the previously reported antisymmetric magnetoresistance due to thickness inhomogeneity. Notably, at lower temperatures, we observed an unconventional Hall effect (UHE), which can be attributed to the Dzyaloshinskii-Moriya interaction (DMI) resulting from the non-coplanar magnetic moment structure. The pronounced influence of sample thickness on magneto-transport properties underscores the competition between magnetic anisotropy and DMI in Fe5-xGeTe2 flakes with varying thicknesses. Our findings provide a deeper understanding of the magneto-transport behavior of the exotic magnetic structure in 2D ferromagnetic materials, which may benefit future spintronic device applications.

Optical design of a monolithic compressed folding imaging lens for infrared/laser dual-band.

In order to realize the miniaturization of the dual-band system, the monolithic compressed folding imaging lens (CFIL) is designed for infrared/laser dual-band in this paper. The relationship among the back focal length, field of view, pupil diameter, and central obscuration of the CFIL are derived. The design method of the dual-band CFIL is given, and the stray light of the CFIL can be suppressed by the double-layer hood structure. According to the design method of the CFIL, the infrared/laser dual-band can be applied by a monolithic optical element. The design results show that the minimum MTF for all fields of view in the infrared band is greater than 0.125 at 42lp/mm, the spot uniformity in the laser band is greater than 90%, and the total system length is only 0.305 times the focal length. After tolerance analysis, the MTF of CFIL is greater than 0.1, and the spot diagram is less than 880µm. The working temperature of the system is -20∼50°C, and the compensation distance is given. After stray light optimization, The point source transmittance (PST) value in the infrared band is reduced by 2 to 4 orders of magnitude, and the PST value in the laser band is reduced by 1 to 5 orders of magnitude. Compared with the traditional coaxial reflective system, the infrared/laser dual-band CFIL has only one lens, and the optical structure is compact. It provides a new idea for the integration and miniaturization of the multi-band system.

Controllable adhesive mechanisms via the internal fibers in soft footpads of honeybees.

The dynamic adhesive systems in nature have served as inspirations for the development of intelligent adhesive surfaces. However, the mechanisms underlying the rapid controllable contact adhesion observed in biological systems have never been adequately explained. Here, the control principle for the unfolding adhesive footpads (alterable contact area) of honeybees is investigated. The footpads can passively unfold, even without neuro-muscular reflexes, in response to specific dragging activity (generating shear force) toward their bodies. This passive unfolding is attributed to the structural features of the soft footpads, which cooperate closely with shear force. Then, the hierarchical structures supported by numerous branching fibers were observed and analyzed. Experimental and theoretical findings demonstrated that shear force can decrease fibril angles with respect to the shear direction, which consequently induces the rotation of the interim contact area of the footpads and achieves their passive unfolding. Furthermore, the decrease in fibril angles can lead to an increase in the liquid pressure within the footpads, and subsequently enhance their unfolding. This study presents a novel approach for passively controlling the contact areas in adhesive systems, which can be applied to develop various bioinspired switchable adhesive surfaces.

Intracellular Activity of Poly (DL-Lactide-co-Glycolide) Nanoparticles Encapsulated with Prothionamide, Pyrazinamide, Levofloxacin, Linezolid, or Ethambutol on Multidrug-Resistant Mycobacterium tuberculosis.

BACKGROUND: Multidrug-resistant Mycobacterium tuberculosis (MDR-TB) is a major cause of death amongst tuberculosis patients. Nanomedicine avoids some limitations of conventional drug treatment and increases therapeutic efficacy against bacterial infections. However, the effect of anti-TB drug nanoparticle (NP) compounds in anti-TB regimens against MDR-TB remains unclear. OBJECTIVE: The objective of this article is to prepare levofloxacin, linezolid, ethambutol, prothionamide, and pyrazinamide encapsulated NPs and to evaluate their therapeutic efficacy against MDR-TB in macrophages. METHODS: Drug-loaded PLGA NPs were prepared by the multiple emulsion method. The colocalization, intracellular release, and anti-TB activity of these NPs were investigated on cultured macrophages. The immune phenotype of the macrophages, including their mitochondrial membrane potential, reactive oxygen species (ROS), and nitric oxide (NO) production, was evaluated following treatment with NPs or free drug compounds. RESULTS: All drug-loaded PLGA NPs were spherical in shape, 150 to 210 nm in size, and showed 14.22% to 43.51% encapsulation efficiencies and long-duration release. Drug-loaded PLGA NPs were mainly distributed in the cytoplasm of macrophages, showed high cellular compatibility, and maintained their concentration for at least 13 days. Compared with the free drug compounds, the number of colonies after exposure to PLGA NP compounds was significantly less. The enhanced antibacterial activity of the NP compounds may be due to the enhanced levels of ROS and NO and the increased early apoptosis stress within M. tuberculosis-infected macrophages additionally. CONCLUSION: The application of PLGA NP compounds not only enhances drug efficacy but also induces innate bactericidal events in macrophages, confirming this as a promising approach for MDR-TB therapy.

Low Temperature Plasma Jet Affects Acute Skin Wounds in Diabetic Mice Through Reactive Components.

As a common complication of diabetes, diabetic foot ulcers serious affect the life quality even lead to amputation if it's not properly treated. In this paper, we developed a Low Temperature Plasma Jet (LTPJ) system for treating diabetic foot ulcers on streptozotocin-induced diabetic mice. This system generates time-dependent reactive nitrogen and oxygen species (RNOS), which have temperature below 40°C. The wound area of normal mice was significantly reduced after LTPJ treatment. Histological and immunohistochemistry analysis showed faster deposition of collagen and more vessel formation both in plasma-treated normal and diabetic mice on Day 3. However, diabetic wounds showed poor collagen deposition and angiogenesis on Day 8, which might be the reason of slow wound healing. Reactive nitrogen species (RNS) that generated by LTPJ can promote endogenous nitric oxide (NO) production in diabetic wounds, thus promoting inflammation, stromal deposition, angiogenesis, cell proliferation and remodeling, while excess reactive oxygen species (ROS) will exacerbate oxidative stress in wound tissues of diabetic mice. In conclusion, LTPJ improved acute wound healing in normal mice, increased collagen deposition and angiogenesis in initial diabetic wound healing, but had no significant effect on diabetic wound healing rate.

Antileukemic effects of topoisomerase I inhibitors mediated by de-SUMOylase SENP1.

SUMO-specific proteases (SENPs) play pivotal roles in maintaining the balance of SUMOylation/de-SUMOylation and in SUMO recycling. Deregulation of SENPs leads to cellular dysfunction and corresponding diseases. As a key member of the SENP family, SENP1 is highly correlated with various cancers. However, the potential role of SENP1 in leukemia, especially in acute lymphoblastic leukemia (ALL), is not clear. This study shows that ALL cells knocking down SENP1 display compromised growth rather than significant alterations in chemosensitivity, although ALL relapse samples have a relatively higher expression of SENP1 than the paired diagnosis samples. Camptothecin derivatives 7-ethylcamptothecin (7E-CPT, a monomer compound) and topotecan (TPT, an approved clinical drug) induce specific SENP1 reduction and severe apoptosis of ALL cells, showing strong anticancer effects against ALL. Conversely, SENP1 could attenuate this inhibitory effect by targeting DNA topoisomerase I (TOP1) for de-SUMOylation, indicating that specific reduction in SENP1 induced by 7E-CPT and/or topotecan inhibits the proliferation of ALL cells.

Development of a series of novel Mcl-1 inhibitors bearing an indole carboxylic acid moiety.

The B cell lymphoma protein 2 (Bcl-2) family proteins regulate cell apoptosis by participating in the endogenous apoptosis pathway. As an important anti-apoptotic protein, Myeloid cell leukemia 1 (Mcl-1) is overexpressed in a variety of tumor cells, and targeting this protein has been a promising strategy for cancer therapy. Herein, based on the 1H-indole-5-carboxylic acid structure previously discovered, we have developed a series of novel compounds with increased affinities and selectivity toward Mcl-1 through structure-based drug design. Among those compounds, 26 exerted relatively better affinity and selectivity for Mcl-1 with moderate inhibition in HL-60 cells. Mechanism studies showed that compound 26 could induce cancer cells apoptosis in an Mcl-1-dependent manner. It also exhibited good microsomal and plasma stability with acceptable pharmacokinetics profiles. Furthermore, treatment with target compound in a 4T1 xenograft mouse model significantly suppressed the tumor growth. Overall, the small molecule described herein represents a promising Mcl-1 inhibitor for further study.

A γ-glutamyl hydrolase lacking the signal peptide confers susceptibility to folates/antifolates in acute lymphoblastic leukemia cells.

A key cofactor of several enzymes implicated in DNA synthesis, repair, and methylation, folate has been shown to be required for normal cell growth and replication and is the basis for cancer chemotherapy using antifolates. γ-Glutamyl hydrolase (GGH) catalyzes the removal of γ-polyglutamate tails of folylpoly-/antifolylpoly-γ-glutamates to facilitate their export out of the cell, thereby maintaining metabolic homeostasis of folates or pharmacological efficacy of antifolates. However, the factors that control or modulate GGH function are not well understood. In this study, we show that intact GGH is not indispensable for the chemosensitivity and growth of acute lymphoblastic leukemia (ALL) cells, whereas GGH lacking N-terminal signal peptide (GGH-ΔN ) confers the significant drug resistance of ALL cells to the antifolates MTX and RTX. In addition, ALL cells harboring GGH-ΔN show high susceptibility to the change in folates, and glycosylation is not responsible for these phenotypes elicited by GGH-ΔN . Mechanistically, the loss of signal peptide enhances intracellular retention of GGH and its lysosomal disposition. Our findings clearly define the in vivo role of GGH in ALL cells and indicate a novel modulation of the GGH function, suggesting new avenues for ALL treatment in future.

WNT5A Enhances LH-Mediated Expression of HAS2 in Granulosa Cells.

In adult ovary, WNT5A is involved in follicular responses to gonadotropins and necessary for ovarian follicle development. However, the mechanism by which gonadotropins regulate WNT5A and the role of WNT5A in modulating follicular responses to gonadotropins are unclear. In mice, we discovered that the expression of Wnt5a was increased in granulosa cells of mouse ovaries during ovulation, and regulated by gonadotropin-activated intra-ovarian cytokine interleukin 6 (IL6). Using human granulosa-like KGN cells, we confirmed that forskolin plus phorbol myristate acetate (PMA) which mimic the luteinizing hormone (LH) action induced the expression of WNT5A and cumulus expansion gene HAS2. However, this effect was suppressed by a NF-κB pathway inhibitor. Inhibition of NF-κB pathway also blocked the activation of WNT5A signaling components ROR2 and JNK. Moreover, exogenous WNT5A enhanced the expression of HAS2 in KGN cells through JNK and AKT signaling pathways. Knockdown of WNT5A expression by siRNA disrupted LH-mediated expression of HAS2. Our findings indicate that WNT5A could be a fine tuner for LH-induced HAS2 expression in ovarian granulosa cells.

ORP4L is a prerequisite for the induction of T-cell leukemogenesis associated with human T-cell leukemia virus 1.

Human T-cell leukemia virus 1 (HTLV-1) causes adult T-cell leukemia (ATL), but the mechanism underlying its initiation remains elusive. In this study, ORP4L was expressed in ATL cells but not in normal T-cells. ORP4L ablation completely blocked T-cell leukemogenesis induced by the HTLV-1 oncoprotein Tax in mice, whereas engineering ORP4L expression in T-cells resulted in T-cell leukemia in mice, suggesting the oncogenic properties and prerequisite of ORP4L promote the initiation of T-cell leukemogenesis. For molecular insight, we found that loss of miR-31 caused by HTLV-1 induced ORP4L expression in T-cells. ORP4L interacts with PI3Kδ to promote PI(3,4,5)P3 generation, contributing to AKT hyperactivation; NF-κB-dependent, p53 inactivation-induced pro-oncogene expression; and T-cell leukemogenesis. Consistently, ORP4L ablation eliminates human ATL cells in patient-derived xenograft ATL models. These results reveal a plausible mechanism of T-cell deterioration by HTLV-1 that can be therapeutically targeted.

Regulation on Citrate Influx and Metabolism through Inhibiting SLC13A5 and ACLY: A Novel Mechanism Mediating the Therapeutic Effects of Curcumin on NAFLD.

Upregulated de novo lipogenesis (DNL) plays a pivotal role in the progress of the nonalcoholic fatty liver disease (NAFLD). Cytoplasmic citrate flux, mediated by plasma membrane citrate transporter (SLC13A5), mitochondrial citrate carrier (SLC25A1), and ATP-dependent citrate lyase (ACLY), determines the central carbon source for acetyl-CoA required in DNL. Curcumin, a widely accepted dietary polyphenol, can attenuate lipid accumulation in NAFLD. Here, we first investigated the lipid-lowering effect of curcumin against NAFLD in oleic and palmitic acid (OPA)-induced primary mouse hepatocytes and high-fat plus high-fructose diet (HFHFD)-induced mice. Curcumin profoundly attenuated OPA- or HFHFD-induced hyperlipidemia and aberrant hepatic lipid deposition via modulating the expression and function of SLC13A5 and ACLY. The possible mechanism of curcumin on the citrate pathway was investigated using HepG2 cells, HEK293T cells transfected with human SLC13A5, and recombinant human ACLY. In OPA-stimulated HepG2 cells, curcumin rectified the dysregulated expression of SLC13A5/ACLY possibly via the AMPK-mTOR signaling pathway. Besides, curcumin also functionally inhibited both citrate transport and metabolism mediated by SLC13A5 and ACLY, respectively. These findings confirm that curcumin improves the lipid accumulation in the liver by blocking citrate disposition and hence may be used to prevent NAFLD.

Design, synthesis and biological evaluation of dual Bcl-2/Mcl-1 inhibitors bearing 2-(1H-indol-4-yl)benzoic acid scaffold.

The anti-apoptotic protein inhibitors of the B cell lymphoma 2 (Bcl-2) family have been developed as new anticancer therapies. Numerous studies illustrated the great potential in the development of dual Bcl-2/myeloid cell leukemia 1 (Mcl-1) inhibitors. Herein, we reported a series of Bcl-2/Mcl-1 inhibitors that optimized from a hit compound 1 via structure-based rational design. The biological evaluation suggested that most compounds exhibited potent binding affinities at submicromolar to both Bcl-2 and Mcl-1 without any Bcl-xL binding affinities, especially compound 9o, with a Ki value of 0.07 µM to Mcl-1 and 0.66 µM to Bcl-2, that has great potential for developing dual inhibitors targeting Bcl-2 and Mcl-1.

Initiation of oogenesis and meiosis in the fetal ovary depends on Dennd1a-mediated production of Wnt5a and retinoic acid from the somatic niches.

BACKGROUND: The DENN (differentially expressed in neoplastic versus normal cells) domain containing 1A (Dennd1a), a guanine nucleotide exchange factor (GEF) for the small GTPase Rab35, is essential for mouse embryogenesis. Disruption of Dennd1a impairs the migration and differentiation of fetal germ cells. In the present study, we further elucidated the role of Dennd1a in oogenesis and meiosis in the fetal ovary. RESULTS: Ablation of Dennd1a disrupted the mRNA expression of Sohlh2, Figla, Stra8, and Rec8 in the ovary of Dennd1a-/- mutants at E13.5. Using ex vivo culture of E12.5 female gonads and adenoviral Dennd1a shRNA infection, we demonstrated that transcription of Sohlh2, Figla, Stra8 and Rec8 were not activated in the fetal ovary lacking Dennd1a. Dennd1a in the somatic cells might stimulate Sohlh2 expression at early stage of oocyte differentiation via regulating Wnt5a synthesis. On the other hand, meiotic initiation of the fetal germ cells required Dennd1a-mediated RA production from the somatic cells, which induced the expression of Stra8 and Rec8. CONCLUSIONS: Dennd1a could be involved in multiple signal pathways in the somatic cells that are critical for various processes of oogenesis and meiosis in the fetal ovary.

Tanshinone IIA prevents LPS-induced inflammatory responses in mice via inactivation of succinate dehydrogenase in macrophages.

Metabolic reprogramming is associated with NLRP3 inflammasome activation in activated macrophages, contributing to inflammatory responses. Tanshinone IIA (Tan-IIA) is a major constituent from Salvia miltiorrhiza Bunge, which exhibits anti-inflammatory activity. In this study, we investigated the effects of Tan-IIA on inflammation in macrophages in focus on its regulation of metabolism and redox state. In lipopolysaccharides (LPS)-stimulated mouse bone marrow-derived macrophages (BMDMs), Tan-IIA (10 µM) significantly decreased succinate-boosted IL-1ß and IL-6 production, accompanied by upregulation of IL-1RA and IL-10 release via inhibiting succinate dehydrogenase (SDH). Tan-IIA concentration dependently inhibited SDH activity with an estimated IC50 of 4.47 µM in LPS-activated BMDMs. Tan-IIA decreased succinate accumulation, suppressed mitochondrial reactive oxygen species production, thus preventing hypoxia-inducible factor-1α (HIF-1α) induction. Consequently, Tan-IIA reduced glycolysis and protected the activity of Sirtuin2 (Sirt2), an NAD+-dependent protein deacetylase, by raising the ratio of NAD+/NADH in activated macrophages. The acetylation of α-tubulin was required for the assembly of NLRP3 inflammasome; Tan-IIA increased the binding of Sirt2 to α-tubulin, and thus reduced the acetylation of α-tubulin, thus impairing this process. Sirt2 knockdown or application of Sirt2 inhibitor AGK-2 (10 µM) neutralized the effects of Tan-IIA, suggesting that Tan-IIA inactivated NLRP3 inflammasome in a manner dependent on Sirt2 regulation. The anti-inflammatory effects of Tan-IIA were observed in mice subjected to LPS challenge: pre-administration of Tan-IIA (20 mg/kg, ip) significantly attenuated LPS-induced acute inflammatory responses, characterized by elevated IL-1ß but reduced IL-10 levels in serum. The peritoneal macrophages isolated from the mice displayed similar metabolic regulation. In conclusion, Tan-IIA reduces HIF-1α induction via SDH inactivation, and preserves Sirt2 activity via downregulation of glycolysis, contributing to suppression of NLRP3 inflammasome activation. This study provides a new insight into the anti-inflammatory action of Tan-IIA from the respect of metabolic and redox regulation.

Racial disparities in survival outcomes among breast cancer patients by molecular subtypes.

PURPOSE: Differences in tumor biology, genomic architecture, and health care delivery patterns contribute to the breast cancer mortality gap between White and Black patients in the US. Although this gap has been well documented in previous literature, it remains uncertain how large the actual effect size of race is for different survival outcomes and the four breast cancer subtypes. METHODS: We established a breast cancer patient cohort at the University of Chicago Comprehensive Cancer Center. We chose five major survival outcomes to study: overall survival, recurrence-free survival, breast-cancer-specific survival, time-to-recurrence and post-recurrence survival. Cox proportional hazards models were used to estimate the hazard ratios between Black and White patients, adjusting for selected patient, tumor, and treatment characteristics, and also stratified by the four breast cancer subtypes. RESULTS: The study included 2795 stage I-III breast cancer patients (54% White and 38% Black). After adjusting for selected patient, tumor and treatment characteristics, Black patients still did worse than White patients in all five survival outcomes. The racial difference was highest within the HR-/HER2+ subgroup, in both overall survival (hazard ratio = 4.00, 95% CI 1.47-10.86) and recurrence-free survival (hazard ratio = 3.00, 95% CI 1.36-6.60), adjusting for age at diagnosis, cancer stage, and comorbidities. There was also a significant racial disparity within the HR+/HER2- group in both overall survival and recurrence-free survival. CONCLUSIONS: Our study confirmed that racial disparity existed between White and Black breast cancer patients in terms of both survival and recurrence, and found that this disparity was largest among HR-/HER2+ and HR+/HER2- patients.

SUMOylation involves in ß-arrestin-2-dependent metabolic regulation in breast cancer cell.

ß-arrestin-2, a multifunctional adaptor protein, was originally identified as a negative regulator of G protein-mediated signaling. We previously revealed that SUMOylation as a novel mechanism modulates ß-arrestin-2-mediated IL-1R/TRAF6 signaling. However, the potential role of ß-arrestin-2 SUMOylation in tumor cells was incompletely explored. In this study, we showed that SUMOylation deficiency of ß-arrestin-2 resulted in slower migration of breast cancer cells, but little effect on the cell proliferation. Importantly, our data indicated that SUMOylation involves in ß-arrestin-2-dependent metabolic regulation, suggesting a potent regulatory pattern for ß-arrestin-2-mediated biological functions of tumor cells.

Radiogenomics of breast cancer using dynamic contrast enhanced MRI and gene expression profiling.

BACKGROUND: Imaging techniques can provide information about the tumor non-invasively and have been shown to provide information about the underlying genetic makeup. Correlating image-based phenotypes (radiomics) with genomic analyses is an emerging area of research commonly referred to as "radiogenomics" or "imaging-genomics". The purpose of this study was to assess the potential for using an automated, quantitative radiomics platform on magnetic resonance (MR) breast imaging for inferring underlying activity of clinically relevant gene pathways derived from RNA sequencing of invasive breast cancers prior to therapy. METHODS: We performed quantitative radiomic analysis on 47 invasive breast cancers based on dynamic contrast enhanced 3 Tesla MR images acquired before surgery and obtained gene expression data by performing total RNA sequencing on corresponding fresh frozen tissue samples. We used gene set enrichment analysis to identify significant associations between the 186 gene pathways and the 38 image-based features that have previously been validated. RESULTS: All radiomic size features were positively associated with multiple replication and proliferation pathways and were negatively associated with the apoptosis pathway. Gene pathways related to immune system regulation and extracellular signaling had the highest number of significant radiomic feature associations, with an average of 18.9 and 16 features per pathway, respectively. Tumors with upregulation of immune signaling pathways such as T-cell receptor signaling and chemokine signaling as well as extracellular signaling pathways such as cell adhesion molecule and cytokine-cytokine interactions were smaller, more spherical, and had a more heterogeneous texture upon contrast enhancement. Tumors with higher expression levels of JAK/STAT and VEGF pathways had more intratumor heterogeneity in image enhancement texture. Other pathways with robust associations to image-based features include metabolic and catabolic pathways. CONCLUSIONS: We provide further evidence that MR imaging of breast tumors can infer underlying gene expression by using RNA sequencing. Size and shape features were appropriately correlated with proliferative and apoptotic pathways. Given the high number of radiomic feature associations with immune pathways, our results raise the possibility of using MR imaging to distinguish tumors that are more immunologically active, although further studies are necessary to confirm this observation.

Antimicrobial Activity of Quinazolin Derivatives of 1,2-Di(quinazolin-4-yl)diselane against Mycobacteria.

Mycobacterium tuberculosis (M. tuberculosis) is one of the leading causes of morbidity and mortality. Currently, the emergence of drug resistance has an urgent need for new drugs. In previous study, we found that 1,2-di(quinazolin-4-yl)diselane (DQYD), a quinazoline derivative, has anticancer activities against many cancers. However, whether DQYD has the activity of antimycobacterium is still little known. Here our results show that DQYD has a similar value of the minimum inhibitory concentration with clinical drugs against mycobacteria and also has the ability of bacteriostatic activity with dose-dependent and time-dependent manner. Furthermore, the activities of DQYD against M. tuberculosis are associated with intracellular ATP homeostasis. Meanwhile, mycobacterium DNA damage level was increased after DQYD treatment. But there was no correlation between survival of mycobacteria in the presence of DQYD and intercellular reactive oxygen species. This study enlightens the possible benefits of quinazoline derivatives as potential antimycobacterium compounds and furtherly suggests a new strategy to develop new methods for searching antituberculosis drugs.