Near-infrared fluorescent probes for the detection of cancer-associated proteases

[Image: see text] Proteases are enzymes capable of catalyzing protein breakdown, which is critical across many biological processes. There are several families of proteases, each of which perform key functions through the degradation of specific proteins. As our understanding of cancer improves, it has been demonstrated that several proteases can be overactivated during the progression of cancer and contribute to malignancy. Optical imaging systems that employ near-infrared (NIR) fluorescent probes to detect protease activity offer clinical promise, both for early detection of cancer as well as for the assessment of personalized therapy. In this Review, we review the design of NIR probes and their successful application for the detection of different cancer-associated proteases

Boosting Semi-Supervised Learning with Contrastive Complementary Labeling

Semi-supervised learning (SSL) has achieved great success in leveraging a large amount of unlabeled data to learn a promising classifier. A popular approach is pseudo-labeling that generates pseudo labels only for those unlabeled data with high-confidence predictions. As for the low-confidence ones, existing methods often simply discard them because these unreliable pseudo labels may mislead the model. Nevertheless, we highlight that these data with low-confidence pseudo labels can be still beneficial to the training process. Specifically, although the class with the highest probability in the prediction is unreliable, we can assume that this sample is very unlikely to belong to the classes with the lowest probabilities. In this way, these data can be also very informative if we can effectively exploit these complementary labels, i.e., the classes that a sample does not belong to. Inspired by this, we propose a novel Contrastive Complementary Labeling (CCL) method that constructs a large number of reliable negative pairs based on the complementary labels and adopts contrastive learning to make use of all the unlabeled data. Extensive experiments demonstrate that CCL significantly improves the performance on top of existing methods. More critically, our CCL is particularly effective under the label-scarce settings. For example, we yield an improvement of 2.43% over FixMatch on CIFAR-10 only with 40 labeled data.Comment: typos corrected, 5 figures, 3 tables

Ethan

In a not too distant future, a technologically advanced country faces a serious problem of population replacement as her individualistic and highly educated citizens reject the idea of procreation. After several failed attempts at encouraging its citizens to procreate, the highly efficient government came up with a single magical solution of the Labour Supplementary Program (LSP) to literally grow the Nation’s population. All healthy citizens who do not have children are required to contribute their sperms and ovaries to the LSP. This program uses advanced scientific technology to artificially engineer the entire process of human growth. Humans are treated as mere labour, a product and nothing more. Babies can now be mass- produced within individual Artificial Gestation Units (AGUs) (refer Appendix) –man-made uterus-- and each child is able to grow at an exponential rate relative to a child by natural birth. In a twist of fate, Vogt, a career-driven scientist develops a father-son bond with one of his specimens and is faced with a dilemma of having to choose between saving his genetically defected “son” from extermination and fulfilling his duties as Head of the LSP.Bachelor of Communication Studie

Identification and Validation of a Stable Major-Effect Quantitative Trait Locus for Kernel Number per Spike on Chromosome 2D in Wheat (<i>Triticum aestivum</i> L.)

A recombinant inbred line population including 371 lines was developed by a high kernel number per spike (KNPS) genotype T1208 and a low KNPS genotype Chuannong18 (CN18). A genetic linkage map consisting of 11,583 markers was constructed by the Wheat55K SNP Array. The quantitative trait loci (QTLs) related to KNPS were detected in three years. Eight, twenty-seven, and four QTLs were identified using the ICIM-BIP, ICIM-MET, and ICIM-EPI methods, respectively. One QTL, QKnps.sau-2D.1, which was mapped on chromosome 2D, can explain 18.10% of the phenotypic variation (PVE) on average and be considered a major and stable QTL for KNPS. This QTL was located in a 0.89 Mb interval on chromosome 2D and flanked by the markers AX-109283238 and AX-111606890. Moreover, KASP-AX-111462389, a Kompetitive Allele-Specific PCR (KASP) marker which closely linked to QKnps.sau-2D.1, was designed. The genetic effect of QKnps.sau-2D.1 on KNPS was successfully confirmed in two RIL populations. The results also showed that the significant increase of KNPS and 1000-kernel weight (TKW) was caused by QKnps.sau-2D.1 overcoming the disadvantage due to the decrease of spike number (SN) and finally lead to a significant increase of grain yield. In addition, within the interval in which QKnps.sau-2D.1 is located in Chinese Spring reference genomes, only fifteen genes were found, and two genes that might associate with KNPS were identified. QKnps.sau-2D.1 may provide a new resource for the high-yield breeding of wheat in the future

Genesis of the Taolin Pb-Zn deposit in northeastern Hunan Province, South China: constraints from trace elements and oxygen-sulfur-lead isotopes of the hydrothermal minerals

Located in the northeastern Hunan Province of South China, the Taolin Pb-Zn deposit is one of many metallic deposits structurally controlled by extensional faults in the central segment of the Jiangnan Orogen. The deposit occurs in a tectonic breccia zone between the Mufushan pluton and the Neoproterozoic Lengjiaxi Group. Field and microscopic observations reveal that the hydrothermal ore-forming processes at Taolin can be divided into five stages, from early to late: (1) coarse-grained quartz, (2) quartz + fluorite + chlorite + claybank sphalerite (Sp1) + galena + chalcopyrite, (3) quartz + barite + pale-yellow sphalerite (Sp2) + galena + chalcopyrite, (4) quartz +/- chalcopyrite, and (5) fine-grained quartz, in which the stages 2 and 3 are regarded as the main Pb-Zn-forming events. LA-ICP-MS analyses show that Sp1 has higher contents of Fe, Mn, Co, In, and Sn, but lower contents of Ge and Sb, relative to the Sp2. Trace element concentrations of the sphalerite suggest a medium-low temperature hydrothermal event dominated in the Taolin deposit and that the ore fluids gradually decreased in the estimated average temperature and became relatively oxidized from stages 2 to 3. The delta O-18 values of ore fluids calculated from in situ analysis on the stages 2 and 3 quartz suggest the ore fluids are from a mixture of magmatic and meteoric waters. The delta S-34 values of sulfides/sulfates from stages 2 and 3 mineralization indicate a dominating magmatic affinity for sulfur. Further, lead isotope compositions for the stages 2 and 3 sulfides are similar to those of the Mufushan pluton, indicating that the ore metals may have been derived from the latter. We thus propose that the Taolin deposit precipitated from a medium-low temperature magmatic-hydrothermal system most likely related to the Mufushan pluton

Geochemical variations of the Late Mesozoic granitoids in the southern margin of North China Craton: A possible link to the tectonic transformation from compression to extension

The composition of the continental crust of the North China Craton (NCC) is more felsic than that of the average bulk crust, which is regarded to be the result of the delamination of the thickened lower crust during Mesozoic. However, whether the thickened continental crust existed and when the delamination event happened along the southern margin of the NCC are still debated. Here, we report geochronological, geochemical and Sr-Nd-Hf-Pb isotopic evidence that granitoids from the Late Jurassic Wuzhangshan pluton and the Early Cretaceous Huashani complex were derived by partial melting of the lower crust with different thickness. Our new data shows that the two lithofacies of the Wuzhangshan pluton were mainly formed between ca. 157 and 156Ma, whereas the five lithofacies of the Huashani complex were mainly emplaced between ca. 132 and 125 Ma. The Wuzhangshan pluton and the earlier four lithofacies granitoids of the Huashani complex (ca. 160-125 Ma) both display adakitic geochemical features, which are characterized by as high SiO2 (63.26-72.71 wt%), Al2O3 (13.97-16.89 wt%) and Sr (413-1218 ppm) contents, and low Y (6.30-14.98 ppm) and YbN (1.55-4.43), and high Sr/Y (33-112) and (La/Yb)(N) (11.53-29.72) ratios. They also have high (Sr-87/Sr-86)i (0.7066-0.7086), and low epsilon Nd(t) (-9.9 to -18.8) and epsilon Hf(t) (-11 to -26) values, and two-stage Nd and Hf model ages ranging from 2.4 to 1.7 Ga and 2.7 to 1.7 Ga, respectively. In contrast, the late Early Cretaceous (ca. 125-110 Ma) granitoids have higher SiO2 (71.30-76.78 wt%) and lower Sr (64-333 ppm) contents, and lower Sr/Y (17-29) and (La/Yb)(N) (13.25-18.36) ratios, and similar epsilon Nd(t) (-10 to -16) and relatively higher epsilon Hf(t) (-10 to -14) values. These geochemical variations suggest that the ca.160-125Ma granitoids were most probably produced by partial melting of thickened crust (>45 km) with eclogite, garnet amphibolite or amphibolite residues, whereas that the ca. 125-110 Ma granitoids were formed by partial melting of the thinner crust (<33 km). We thus suggest that the NCC likely underwent a synchronous tectonic transformation at ca. 125 Ma from a compressional setting with thickened crust to an intensive extensional setting with thinner crust at ca. 125 Ma, which demonstrates that the lower crust was most likely delaminated. (c) 2019 International Association for Gondwana Research. Published by Elsevier B.V. All rights reserved

Development of a novel DNA sequencing method not only for hepatitis B virus genotyping but also for drug resistant mutation detection

Abstract Background In HBV-infected patients, different genotypes of the hepatitis B virus influence liver disease progression and response to antiviral therapy. Moreover, long-term antiviral therapy will eventually select for drug-resistant mutants. Detection of mutations associated to antiviral therapy and HBV genotyping are essential for monitoring treatment of chronic hepatitis B patients. Results In this study, a simple method of partial-S gene sequencing using a common PCR amplification was established for genotyping clinical HBV isolates sensitively, which could detect the drug-resistant mutations successfully at the same time. Conclusions The partial S gene sequencing assay developed in this study has potential for application in HBV genotyping and drug resistant mutation detection. It is simpler and more convenient than traditional S gene sequencing, but has nearly the same sensitivity and specificity when compared to S gene sequencing.</p

Relations between different components of rejection sensitivity and adjustment in Chinese children

The goal of the present study was to examine the relations between the cognitive (i.e., expectations) and emotional (i.e., anxiety, anger) components of rejection sensitivity and adjustment among Chinese children. Participants were N = 654 children (grades four to seven) in Shanghai, China. Measures of rejection sensitivity, socio-emotional functioning, and academic achievement were collected via multi-source assessment. Among the results, the anxiety component was associated with psychological problems (e.g., social anxiety, lower self-worth), whereas the anger component was associated with social and behavioral problems (e.g., peer victimization, lower peer preference, total difficulties). Rejection expectations were associated with the widest range of adjustment difficulties. The current findings suggest that rejection sensitivity poses considerable risk for Chinese youth, and that the emotional and cognitive components of rejection sensitivity should be viewed as distinct vulnerabilities for risk. Results are discussed in terms of the unique implications of rejection sensitivity in Chinese culture

A CEP Peptide Receptor-Like Kinase Regulates Auxin Biosynthesis and Ethylene Signaling to Coordinate Root Growth and Symbiotic Nodulation in Medicago truncatula

International audienceBecause of the large amount of energy consumed during symbiotic nitrogen fixation, legumes must balance growth and symbiotic nodulation. Both lateral roots and nodules form on the root system, and the developmental coordination of these organs under conditions of reduced nitrogen (N) availability remains elusive. We show that the Medicago truncatula COMPACT ROOT ARCHITECTURE2 (MtCRA2) receptor-like kinase is essential to promote the initiation of early symbiotic nodulation and to inhibit root growth in response to low N. C-TERMINALLY ENCODED PEPTIDE (MtCEP1) peptides can activate MtCRA2 under N-starvation conditions, leading to a repression of YUCCA2 (MtYUC2) auxin biosynthesis gene expression, and therefore of auxin root responses. Accordingly, the compact root architecture phenotype of cra2 can be mimicked by an auxin treatment or by overexpressing MtYUC2, and conversely, a treatment with YUC inhibitors or an MtYUC2 knockout rescues the cra2 root phenotype. The MtCEP1-activated CRA2 can additionally interact with and phosphorylate the MtEIN2 ethylene signaling component at Ser 643 and Ser 924 , preventing its cleavage and thereby repressing ethylene responses, thus locally promoting the root susceptibility to rhizobia. In agreement with this interaction, the cra2 low nodulation phenotype is rescued by an ein2 mutation. Overall, by reducing auxin biosynthesis and inhibiting ethylene signaling, the MtCEP1/MtCRA2 pathway balances root and nodule development under low-N conditions