A deep-learning-based framework for identifying and localizing multiple abnormalities and assessing cardiomegaly in chest X-ray.

Accurate identification and localization of multiple abnormalities are crucial steps in the interpretation of chest X-rays (CXRs); however, the lack of a large CXR dataset with bounding boxes severely constrains accurate localization research based on deep learning. We created a large CXR dataset named CXR-AL14, containing 165,988 CXRs and 253,844 bounding boxes. On the basis of this dataset, a deep-learning-based framework was developed to identify and localize 14 common abnormalities and calculate the cardiothoracic ratio (CTR) simultaneously. The mean average precision values obtained by the model for 14 abnormalities reached 0.572-0.631 with an intersection-over-union threshold of 0.5, and the intraclass correlation coefficient of the CTR algorithm exceeded 0.95 on the held-out, multicentre and prospective test datasets. This framework shows an excellent performance, good generalization ability and strong clinical applicability, which is superior to senior radiologists and suitable for routine clinical settings.

Ultrasonic-assisted extraction brings high-yield polysaccharides from Kangxian flowers with cosmetic potential.

The purpose of this work was to ameliorate the yield of polysaccharides from Kangxian flowers (PKFs) using ultrasonic-assisted extraction (UAE) and to explore the structural features and cosmetic potential of PKFs obtained under the optimized UAE. According to response surface methodology, the optimal UAE for PKFs were liquid-to-solid ratio of 59: 1 mL/g, ultrasonic power of 404 W, time of 48 min, and temperature of 66℃, under which the yield of PKFs reached 26.8 ± 1.76 %, 2.6-folds higher than hot-water extraction. By comparing the microstructures, it can be seen that ultrasonication exerted great damage on Kangxian flowers to promote the outflow of PKFs. Various analyses revealed that the PKFs extracted with UAE were acidic polysaccharides with relatively lower molecular weights of 0.92 - 76.9 kDa, negatively charged potential of -16.3 mV, and arabinose the dominant monosaccharide followed by galactose. These structural features conferred PKFs pronounced antioxidant, moistureabsorptionandretentionproperties, showing great potential for cosmetic application.

High expression of serine protease 2 (PRSS2) associated with invasion, metastasis, and proliferation in gastric cancer.

BACKGROUND: Accumulating evidence indicates that the occurrence and development of tumors are related to the activation of oncogenes and the inactivation of tumor suppressor genes caused by epigenetic mechanisms. However, the function of serine protease 2 (PRSS2) in gastric cancer (GC) is still unknown. Our study aimed to find a regulation network involved in GC. METHODS: The mRNA data (GSE158662 and GSE194261) of GC and normal tissues were downloaded from the Gene Expression Omnibus (GEO) dataset. Differential expression analysis was performed using R software, and Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted by using Xiantao software. Besides, we used Quantitative Real-time PCR (qPCR) to verify our conclusions. After gene knockdown, cell migration and CCK-8 experiment were carried out to detect the effect of gene on cell proliferation and invasion. RESULTS: Totally, 412 differentially expressed genes (DEGs) were identified from GSE158662 and 94 DEGs were identified from GSE196261. Km-plot database results indicated that PRSS2 exhibited high diagnosis worth for GC. Gene functional annotation enrichment analysis revealed that these hub mRNAs were mainly taken part in the process of tumorigenesis and development. Besides, vitro experiments showed that down-regulation of PRSS2 gene reduced the proliferation and invasion ability of GC cells. CONCLUSIONS: Our results indicated that PRSS2 may play vital roles in the carcinogenesis and progression of GC and can be potential biomarkers for patients with GC.

Microwave-assisted enzymatic extraction brings a notably high yield of polysaccharides from mountain Zizania latifolia.

Mountain Zizania latifolia is produced at scale in China, and the edible swollen culm is exported to many countries, but little attention has been paid to its functional components. In this work, microwave-assisted enzymatic extraction (MAEE) is used for the first time to extract polysaccharides from mountain Z. latifolia swollen culm (PMZL). MAEE conditions optimized by Box-Behnken design-response surface methodology were as follows: 2.4% cellulase, microwaving for 6.0 min at 607 W, with a liquid-to-solid ratio of 63:1 ml g-1 . Under these conditions, a notably high yield of 60.43% ± 1.12% for PMZL was achieved, which was significantly higher (p < 0.01) than from plain-grown varieties. PMZL are naturally occurring sulfated polysaccharide-protein complexes containing 8.46% ± 0.18% proteins and 7.86% ± 0.73% sulfates. PMZL comprises mannose, glucosamine, rhamnose, glucose, galactose, and arabinose at molar ratios of 3.80:2.68:1.00:17.41:5.12:2.91, with a weight-average molecular weight of 1569,219 Da and a number-average molecular weight of 364,088 Da. The surface morphology of PMZL is composed of tightly packed oval particles, and this kind of promising polysaccharides preferentially scavenges reactive nitrogen species. PRACTICAL APPLICATION: Due to global warming, the land available for planting vegetables is likely to expand to higher areas, so greater attention should now be paid to mountain-grown vegetables. This study provides an efficient way to obtain novel polysaccharides from mountain Zizania latifolia using microwave-assisted enzymatic extraction with a remarkably high yield of 60.4%. This promising source of natural carbohydrates has potential uses in pharmaceutical, nutraceutical, functional foods, cosmetics, and functional materials industries.

ARHGEF3 Associated with Invasion, Metastasis, and Proliferation in Human Osteosarcoma.

BACKGROUND: Osteosarcoma is a malignant bone tumor composed of mesenchymal cells producing osteoid and immature bone. This study is aimed at developing novel potential prognostic biomarkers and constructing a miRNA-mRNA network for progression in osteosarcoma. METHOD: GSE70367 and GSE70414 were obtained in the Gene Expression Omnibus (GEO) database. GEO software and the GEO2R calculation method were used to analyze two gene profiles. The coexpression of differentially expressed miRNAs (DEMs) and genes (DEGs) was identified and searched for in the FunRich database for pathway and ontology analysis. Cytoscape was utilized to construct the mRNA-miRNA network. Survival analysis of identified miRNAs and mRNAs was performed by utilizing the Kaplan-Meier Plotter. Besides, expression levels of DEMs and target mRNAs were verified by performing quantitative real-time PCR (qRT-PCR) and Western blot (WB). RESULTS: Six differentially expressed microRNAs (DEMs) were identified, and 8 target genes were selected after screening. By using the KM Plotter software, miRNA-124 and ARHGEF3 were obviously associated with the overall survival of patients with osteosarcoma. Furthermore, ARHGEF3 was found downregulated in osteosarcoma cells by performing qRT-PCR and WB experiments. Results also showed that downregulated ARHGEF3 may associate with invasion, metastasis, and proliferation. CONCLUSIONS: By using microarray and bioinformatics analysis, DEMs were selected, and a complete miRNA-mRNA network was constructed. ARHGEF3 may act as a therapeutic and prognostic target of osteosarcoma.

Coexistence of craniopharyngioma and meningioma: Two rare cases and literature review.

Most of the craniopharyngioma is considered to derive from residual epithelial cells during the craniopharyngeal canal degeneration. Meningioma accounting for the primary intracranial neoplasm is considered to be mainly derived from cells of arachnoid granulations. Nevertheless, rare cases show coexistence of craniopharyngioma and meningioma.Case 1: A 43-year-old male patient referred to the hospital due to paroxysmal headache combined with blurred vision for 1 month. On physical examination, the visual acuity of left eye was poorer than that of the right eye. The visual acuity of the right eye near the nasal part showed defect.MRI and pathological examination were performed. The patient received intracranial tumor resection. After surgery, the patient showed hormone disorder, followed by corresponding treatment. However, the patient was lost in the 6-month follow-up.Case 2: The 64-year-old male patient presented to our department due to decline of visual acuity within 1 year combined with polydipsia (5,000 ml per day), polyuria and fatigue for 6 months. On physical examination, the bilateral visual acuity showed decline, especially the temporal part which was nearly hemiscotosis. MRI was performed. The adamantinomatous craniopharyngioma was diagnosed with the HE staining findings. The patient received intracranial resection. After surgery, the patient was in a deep coma condition, and was lost in the follow-up.In this case study, we presented 2 patients with coexistence of craniopharyngioma and meningioma. In addition, a complete literature review was carried out to illustrate the studies on coexistence of craniopharyngioma and meningioma. Meanwhile, we tried to explain the possible mechanisms for such condition.

Discovery of new LXRß agonists as glioblastoma inhibitors.

Discovery and optimization of selective liver X receptor ß (LXRß) agonists are challenging due to the high homology of LXRα and LXRß in the ligand-binding domain. There is only one different residue (Val versus Ile) at the ligand-binding pocket of LXRs. With machine learning methods, we identified pan LXR agonists with a novel scaffold (spiro[pyrrolidine-3,3'-oxindole]). Then, we figured out the mechanism of LXR isoform selectivity from co-crystal structures. Based on the mechanism and the new scaffold, LXRß selective agonists were designed and synthesized. This led to the discovery of LXRß agonists 4-7rr, 4-13 and 4-13rr with IC50 values ranging from 1.78 to 6.36 µM against glioblastoma in vitro. Treatment with 50 mg/kg/day of 4-13 for 15 days significantly reduced tumor growth using an in vivo xenograft glioblastoma model.

Early variations in lymphocytes and T lymphocyte subsets are associated with radiation pneumonitis in lung cancer patients and experimental mice received thoracic irradiation.

There were no ideal markers to predict the development of radiation pneumonitis (RP). We want to investigate the value of variations of lymphocytes and T lymphocyte subsets in predicting RP after radiotherapy (RT) of lung cancer based on previous clinical findings. A total of 182 lung cancer patients who received RT were retrospectively analyzed. Circulating lymphocytes and T lymphocyte subsets were measured before, during, and after RT. Patients were evaluated from the start of RT to 6 months post-RT. A mice model with acute radiation-induced lung injury was established and circulating lymphocytes were measured weekly until 8 weeks after irradiation. Univariate and multivariate analyses were adopted to identify risk factors of RP. Lymphocyte levels significantly decreased (P < .001) in patients before RP symptoms developed that also was able to be seen in the mice model and the values recovered during remission of symptoms. The decrease in lymphocyte count reflected the severity of RP. Meanwhile, CD4+  T lymphocyte count was significantly lower during the occurrence of symptoms in patients with RP than in those without RP (P < .001), and it improved along with RP recovery. Levels of lymphocytes and CD4+  T lymphocyte subsets proved as independent predictors of RP. Here we showed that lower peripheral blood levels of lymphocytes and CD4+  T lymphocyte were associated with an increased risk of RP, which was validated by this mice model, and thus are associated with differences in radiation-induced lung toxicity among individuals and help identify those who are susceptible to developing RP after RT.

Binding of human recombinant mutant soluble ectodomain of FGFR2IIIc to c subtype of FGFRs: implications for anticancer activity.

FGFRs are considered essential targets for cancer therapy. We previously reported that msFGFR2c, a Ser252Trp mutant soluble ectodomain of FGFR2IIIc, inhibited tumor growth by blocking FGF signaling pathway. However, the underlying molecular mechanism is still obscure. In this study, we reported that msFGFR2c but not wild-type soluble ectodomain of FGFR2IIIc (wsFGFR2c) could selectively bind to c subtype of FGFRs in the presence of FGF-2. Thermodynamic analysis demonstrated that msFGFR2c bound to wsFGFR2c in the presence of FGF-2 with a K value of 6.61 × 105 M-1. Molecular dynamics simulations revealed that the mutated residue Trp252 of msFGFR2c preferred a π-π interaction with His254 of wsFGFR2c. Concomitantly, Arg255 of msFGFR2c and Glu250 of wsFGFR2c adjusted their conformations and formed three H-bonds. These two interactions therefore stabilized the final structure of wsFGFR2c and msFGFR2c heterocomplex. In FGFR2IIIc-positive/high FGF-2-secreted BT-549 cells, msFGFR2c significantly inhibited the proliferation and induced apoptosis by the blockage of FGF-2-activated FGFRs phosphorylation, also the growth and angiogenesis of its xenograft tumors implanted in chick embryo chorioallantoic membrane model. While weaker the above inhibitory effects of msFGFR2c were observed on FGFR2IIIc-negative/low FGF-2-secreted MCF-7 and MDA-MB-231 cell lines in vitro and in vivo. Moreover, msFGFR2c significantly inhibited the proliferation of FGFR1IIIc-positive NCI-H1299 lung cancer cells by the suppression of FGF-2-induced FGFR1 activation and suppressed the growth of NCI-H1299 transplanted tumors in nude mice. In sum, msFGFR2c is a potential anti-tumor agent targeting FGFR2c/FGFR1c-positive tumor cells. These findings also provide a molecular basis for msFGFR2c to disrupt the activation of FGF signaling.

A new selective fluorescent sensor for Fe3+ based on a pyrazoline derivative.

A new pyrazoline derivative was designed and synthesized. The structure of the pyrazoline was confirmed by single crystal X-ray diffraction and its photophysical properties were studied by absorption and fluorescence spectra. This compound can be used to determine Fe(3+) ion with high selectivity among a series of cations in tetrahydrofuran and even in aqueous tetrahydrofuran. This sensor forms a 1:1 complex with Fe(3+) and displays fluorescent quenching.

A Quantum Chemical Study of the Ground and Excited State Electronic Structures of Carbazole Oligomers with and without Triarylborane Substitutes.

Recent experimental investigation (Reitzenstein and Lambert,Macromolecules, 2009, 42, 773) indicated that the quite different optical properties of 2,7- and 3,6-linkage triarylboryl carbazole oligomers may arise from the different nature of their low-lying excited states: a low-lying delocalized within-backbone excitation in longer 2,7-linked oligomers vs a backbone-to-sidechain charge-transfer (CT) excitation independent of the polymerization length in 3,6-linked oligomers. Here in this paper, two long-range corrected functionals, CAM-B3LYP and ωB97X, are applied together with the traditional B3LYP functional in time-dependent density functional theory (TDDFT) calculations to systematically investigate the low-lying electronic excitations in both oligomers. Our calculations indicate that an extensive conjugation exists between monomer molecular orbitals in 2,7-linked oligomers, which is absent in those of 3,6-linked structures, resulting in a considerable narrowing of the HOMO-LUMO gap of their backbone moiety, while having little effect on the side-chains. CAM-B3LYP and ωB97x calculations confirm that the lowest-energy absorption is a within-backbone excitation in longer 2,7-linked oligomers as opposed to a backbone to side-chain charge transfer excitation in 2,7-linked oligmers of shorter length and 3,6-linked oligomers of any length. All these findings are consistent with the experimental findings and the qualitative energy diagram proposed by Reitzenstein and Lambert.

New Methods for Labeling RGD Peptides with Bromine-76.

Direct bromination of the tyrosine residues of peptides and antibodies with bromine-76, to create probes for PET imaging, has been reported. For peptides that do not contain tyrosine residues, however, a prosthetic group is required to achieve labeling via conjugation to other functional groups such as terminal α-amines or lysine ε-amines. The goal of this study was to develop new strategies for labeling small peptides with Br-76 using either a direct labeling method or a prosthetic group, depending on the available functional group on the peptides. A new labeling agent, N-succinimidyl-3-[(76)Br]bromo-2,6-dimethoxybenzoate ([(76)Br]SBDMB) was prepared for cyclic RGD peptide labeling. N-succinimidyl-2, 6-dimethoxybenzoate was also used to pre-attach a 2, 6-dimethoxybenzoyl (DMB) moiety to the peptide, which could then be labeled with Br-76. A competitive cell binding assay was performed to determine the binding affinity of the brominated peptides. PET imaging of U87MG human glioblastoma xenografted mice was performed using [(76)Br]-BrE[c(RGDyK)](2) and [(76)Br]-BrDMB-E[c(RGDyK)](2). An ex vivo biodistribution assay was performed to confirm PET quantification. The mechanisms of bromination reaction between DMB-c(RGDyK) and the brominating agent CH(3)COOBr were investigated with the SCRF-B3LYP/6-31G* method with the Gaussian 09 program package. The yield for direct labeling of c(RGDyK) and E[c(RGDyK)](2) using chloramine-T and peracetic acid at ambient temperature was greater than 50%. The yield for [(76)Br]SBDMB was over 60% using peracetic acid. The conjugation yields for labeling c(RGDfK) and c(RGDyK) were over 70% using the prosthetic group at room temperature. Labeling yield for pre-conjugated peptides was over 60%. SDMB conjugation and bromination did not affect the binding affinity of the peptides with integrin receptors. Both [(76)Br]Br-E[c(RGDyK)](2) and [(76)Br]BrDMB-E[c(RGDyK)](2) showed high tumor uptake in U87MG tumor bearing mice. The specificity of the imaging tracers was confirmed by decreased tumor uptake after co-administration of unlabeled dimeric RGD peptides. The energy barrier of the transition state of bromination for the dimethoxybenzoyl group was about 9 kcal/mol lower than that for the tyrosine residue. In conclusion, the newly developed N-succinimidyl-2, 6-dimethoxybenzoate molecule can be used either for one step labeling through pre-conjugation or as the precursor for a Br-76 labeled prosthetic group for indirect labeling. Radiobromination on a dimethoxybenzoyl group has selectivity over radiobromination on tyrosine. The energy barrier difference of the transition states of bromination between the dimethoxybenzoyl group and the tyrosine residue may account for the reaction selectivity when both groups are present in the same molecule.

Communication: A dramatic transition from nonferromagnet to ferromagnet in finite fused-azulene chain.

One-dimensional fused-azulene oligomers (n = 2-6) are studied with the effective valence bond as well as density functional theory methods. A nonferromagnetic (closed-shell singlet) to ferromagnetic (triplet) ground state transformation is witnessed with increasing length of oligomers. The computational results are interpreted in terms of spin coupling between the unpaired electrons of two nonbonding molecular orbitals localized, respectively, on the top and bottom chains of the oligomers. The present study provides a theoretical suggestion for understanding the ferromagnetic spin polarizations that has been observed very recently in graphene nanoribbons.

Experimentation and theoretic calculation of a BODIPY sensor based on photoinduced electron transfer for ions detection.

A boron-dipyrromethene (BODIPY)-based fluorescence probe with a N,N'-(pyridine-2, 6-diylbis(methylene))-dianiline substituent (1) has been prepared by condensation of 2,6-pyridinedicarboxaldehyde with 8-(4-amino)-4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene and reduction by NaBH(4). The sensing properties of compound 1 toward various metal ions are investigated via fluorometric titration in methanol, which show highly selective fluorescent turn-on response in the presence of Hg(2+) over the other metal ions, such as Li(+), Na(+), K(+), Ca(2+), Mg(2+), Pb(2+), Fe(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+), Cd(2+), Ag(+), and Mn(2+). Computational approach has been carried out to investigate the mechanism why compound 1 provides different fluorescent signal for Hg(2+) and other ions. Theoretic calculations of the energy levels show that the quenching of the bright green fluorescence of boradiazaindacene fluorophore is due to the reductive photoinduced electron transfer (PET) from the aniline subunit to the excited state of BODIPY fluorophore. In metal complexes, the frontier molecular orbital energy levels changes greatly. Binding Zn(2+) or Cd(2+) ion leads to significant decreasing of both the HOMO and LUMO energy levels of the receptor, thus inhibit the reductive PET process, whereas an oxidative PET from the excited state fluorophore to the receptor occurs, vice versa, which also quenches the fluorescence. However, for 1-Hg(2+) complex, both the reductive and oxidative PETs are prohibited; therefore, strong fluorescence emission from the fluorophore can be observed experimentally. The agreement of the experimental results and theoretic calculations suggests that our calculation method can be applicable as guidance for the design of new chemosensors for other metal ions.