Magnification-independent Histopathological Image Classification with Similarity-based Multi-scale Embeddings

The classification of histopathological images is of great value in both cancer diagnosis and pathological studies. However, multiple reasons, such as variations caused by magnification factors and class imbalance, make it a challenging task where conventional methods that learn from image-label datasets perform unsatisfactorily in many cases. We observe that tumours of the same class often share common morphological patterns. To exploit this fact, we propose an approach that learns similarity-based multi-scale embeddings (SMSE) for magnification-independent histopathological image classification. In particular, a pair loss and a triplet loss are leveraged to learn similarity-based embeddings from image pairs or image triplets. The learned embeddings provide accurate measurements of similarities between images, which are regarded as a more effective form of representation for histopathological morphology than normal image features. Furthermore, in order to ensure the generated models are magnification-independent, images acquired at different magnification factors are simultaneously fed to networks during training for learning multi-scale embeddings. In addition to the SMSE, to eliminate the impact of class imbalance, instead of using the hard sample mining strategy that intuitively discards some easy samples, we introduce a new reinforced focal loss to simultaneously punish hard misclassified samples while suppressing easy well-classified samples. Experimental results show that the SMSE improves the performance for histopathological image classification tasks for both breast and liver cancers by a large margin compared to previous methods. In particular, the SMSE achieves the best performance on the BreakHis benchmark with an improvement ranging from 5% to 18% compared to previous methods using traditional features

Superconductivity in boron-doped carbon nanotube networks

By using the five Angstrom diameter pores of calcined zeolite as the template, we have fabricated boron doped carbon nanotube networks via the chemical vapor deposition method. Raman data indicate the network to comprise segments of interconnected carbon nano tubes. Transport measurements showed a superconducting transition initiating at 40K, with a sharp downturn around 20K to a low resistance state at 2K, accompanied by a low resistance plateau in the current voltage characteristic, fluctuating around zero resistance. Magnetic measurements exhibited the Meissner effect characteristic of thin superconducting wire networks in which the superconducting wire radius is much smaller than the London penetration length. At low magnetic field, the negative diamagnetic susceptibility was observed to persist beyond 200K. The transport and magnetic data are reconciled on the basis of a physical model based on weak links comprising short, one-dimensional superconducting nano tubes, that govern the global transport behavior.Comment: 22 pages, 6 figures in the main text, 2 figures in appendices, 37 reference

Chrysin ameliorates synovitis and fibrosis of osteoarthritic fibroblast-like synoviocytes in rats through PERK/TXNIP/NLRP3 signaling

Objective: Synovitis and fibrosis are common pathological features of knee osteoarthritis (KOA). The interaction of synovitis and fibrosis can promote KOA progression. Chrysin (CHR), a natural flavonoid, may treat inflammation and prevent fibrosis. However, the effect and mechanism of CHR in KOA synovitis and fibrosis remains unclear.Methods: The KOA model was established in male SD rats by anterior cruciate ligament transection (ACLT), and histological analysis was used to evaluate synovitis and fibrosis. IL-6, IL-1β and TNF-α mRNA expression in synovial tissue was measured by qRT‒PCR. Immunohistochemistry (IHC) was performed to detect GRP78, ATF-6 and TXNIP expression in vivo. Synovial fibroblasts (SFs) were treated with TGF-β1 to stimulate the inflammatory response and fibrosis. CCK-8 assays were used to detect the viability of CHR-treated SFs. The IL-1β level was detected by immunofluorescence analysis. Coimmunoprecipitation (Co-IP) and double immunofluorescence colocalization were used to detect the physiological interaction between TXNIP and NLRP3. The expression of fibrosis-related mediators and PERK/TXNIP/NLRP3 signaling molecules was detected by western blotting and qRT-PCR.Results: Four weeks after CHR treatment, pathological sections and associated scores showed that CHR improved synovitis and fibrosis in the ACLT model. In vitro, CHR attenuated the TGF-β1-induced inflammatory response and fibrosis in SFs. Moreover, CHR suppressed the expression of synovial fibrosis markers and PERK/TXNIP/NLRP3 signaling molecules in the synovial tissue of rats with ACLT and cultured SFs. More importantly, we found that CHR inhibited TXNIP-NLRP3 interactions in TGF-β-induced SFs.Conclusion: Our findings indicate that CHR can ameliorate synovitis and fibrosis in KOA. The underlying mechanism may be related to the PERK/TXNIP/NLRP3 signaling pathway

GCTOF-MS Combined LC-QTRAP-MS/MS Reveals Metabolic Difference Between Osteoarthritis and Osteoporotic Osteoarthritis and the Intervention Effect of Erxian Decoction

PurposeOP and OA are chronic bone diseases with high incidence in the middle-aged and elderly populations. The latest research shows that the pathological environment of OP may be involved in the aggravation of the pathological process of OA, and the pathological state of OP plays an important role in the aggravation of OA pathology. EXD is a traditional Chinese medicine decoction that has been used to treat osteoporosis. Therefore, we further study whether OA will be aggravated in the OP environment and whether EXD can alleviate OA by intervening in the OP environment. The purpose of this study was to analyze the effect of OP on OA metabolites by using metabolomic methods and to explore the intervention mechanism of EXD on osteoporotic OA.MethodThirty-two SD rats were randomly divided into normal group, OA group, OP-OA group, and EXD group. EXD was administered by gavage. Histopathological evaluation of cartilage tissue was performed using Saffron fast green and HE staining. Western blot and qRT-PCR were used to detect the expression levels of chondrogenesis genes SOX9, COL2A1, and COMP in cartilage tissue. GC-TOFMS and LC-QTRAP-MS/MS metabolomics methods were used to analyze the changes of metabolites in serum samples of rats in each group.ResultThe slice results showed that the cartilage damage in the OP-OA group was more serious than that in the OA group, which was significantly relieved after EXD intervention, indicating that the cartilage damage in the OP-OA group was more severe than that in the OA group and further reduced the protein and gene expressions of cartilage markers SOX9, COL2A1, and COMP. Thirty-seven substances were identified, and gentiopicroside, emodin, quercetin, and diosmetin were analyzed as possible active components of EXD. EXD treatment significantly reduced cartilage damage and reversed the expression of these markers. Metabolomics showed that EXD attenuated cartilage destruction by modulating the expression of cystine, chenodeoxycholate, and D-Turanose, involving glycolysis/gluconeogenesis, pantothenate, and CoA biosynthesis metabolic pathways.ConclusionThe OP environment may promote the progression of OA through metabolic factors. The benign intervention of EXD in osteoporotic OA involves cystine, chenodeoxycholate, and D-Turanose, and their associated glycolysis/gluconeogenesis, pantothenate, and CoA biosynthesis metabolic pathways. Therefore, we have a deep understanding of the metabolic-related intervention of EXD in osteoporotic OA and are eager to better understand the mechanism of multi-targeted intervention of EXD in bone metabolic lesions

Microbiome analysis and biocontrol bacteria isolation from rhizosphere soils associated with different sugarcane root rot severity

To explore the causal pathogen and the correlated rhizosphere soil microecology of sugarcane root rot, we sampled the sugarcane root materials displaying different disease severity, and the corresponding rhizosphere soil, for systematic root phenotype and microbial population analyses. We found that with increased level of disease severity reflected by above-ground parts of sugarcane, the total root length, total root surface area and total volume were significantly reduced, accompanied with changes in the microbial population diversity and structure in rhizosphere soil. Fungal community richness was significantly lower in the rhizosphere soil samples from mildly diseased plant than that from either healthy plant, or severely diseased plant. Particularly, we noticed that a peculiar decrease of potential pathogenic fungi in rhizosphere soil, including genera Fusarium, Talaromyces and Neocosmospora, with increased level of disease severity. As for bacterial community, Firmicutes was found to be of the highest level, while Acidobacteria and Chloroflexi of the lowest level, in rhizosphere soil from healthy plant compared to that from diseased plant of different severity. FUNGuild prediction showed that the proportion of saprophytic fungi was higher in the rhizosphere soil of healthy plants, while the proportion of pathogenic fungi was higher in the rhizosphere soil of diseased plants. By co-occurrence network analysis we demonstrated the Bacillus and Burkholderia were in a strong interaction with Fusarium pathogen(s). Consistently, the biocontrol and/or growth-promoting bacteria isolated from the rhizosphere soil were mostly (6 out of 7) belonging to Bacillus and Burkholderia species. By confrontation culture and pot experiments, we verified the biocontrol and/or growth-promoting property of the isolated bacterial strains. Overall, we demonstrated a clear correlation between sugarcane root rot severity and rhizosphere soil microbiome composition and function, and identified several promising biocontrol bacteria strains with strong disease suppression effect and growth-promoting properties

On-surface crystallization behaviors of H-bond donor–acceptor complexes at liquid/solid interfaces

Two-dimensional (2D) crystallization behaviors of A-TPCn (n = 4, 6, 10), T3C4, and hydrogen-bonded complexes T3C4@TPCn (n = 4, 6, 10) are investigated by means of scanning tunneling microscope (STM) observations and density functional theory (DFT) calculations. The STM observations reveal that A-TPC4, A-TPC10, and T3C4 self-organize into dumbbell-shaped structures, well-ordered bright arrays, and zigzag structures, respectively. Interestingly, T3C4@TPC10 fails to form the cage-ball structure, whereas T3C4@TPC4 and T3C4@TPC6 co-assemble into cage-ball structures with the same lattice parameters. The filling rates of the balls of these two kinds of cage-ball structures depend heavily on the deposition sequence. As a result, the filling rates of the cages in T3C4/A-TPCn (n = 4, 6) with deposition of T3C4 anterior to A-TPCn are higher than those in A-TPCn/T3C4 (n = 4, 6) with the opposite deposition sequence. Furthermore, lattice defects formed by T3C4 coexist with the cage-ball structures. Moreover, the similar energy per unit area of lattice defects (−0.101 kcal mol–1 Å–2) and the two cage-ball networks (−0.194 and −0.208 kcal mol–1 Å–2, respectively), illustrating the similar stabilities of lattice defects and cage-ball networks, demonstrates the rationality of lattice defects. Combining STM investigations and DFT calculations, this work could provide a useful approach to investigate the 2D crystallization mechanisms of supramolecular liquid crystals on surfaces.This work was supported by the National Basic Research Program of China (No. 2016YFA0200700), the National Natural Science Foundation of China (Nos. 21472029, 11001257, and 21773041), the MINECO-FEDER funds (project MAT2015-66208-C3-1-P), and the Gobierno de Aragon-FSE (E47_17R and B.F grant).Peer reviewe