Recently, a new density-peak-based clustering method, called clustering with local density peaks-based minimum spanning tree (LDP-MST), was proposed, which has several attractive merits, e.g., being ...able to detect arbitrarily shaped clusters and not very sensitive to noise and parameters. Nevertheless, we also found the limitation of LDP-MST in efficiency. Specifically, LDP-MST has <inline-formula><tex-math notation="LaTeX">O(N\log N+M^{2})</tex-math> <mml:math><mml:mrow><mml:mi>O</mml:mi><mml:mo>(</mml:mo><mml:mi>N</mml:mi><mml:mo form="prefix">log</mml:mo><mml:mi>N</mml:mi><mml:mo>+</mml:mo><mml:msup><mml:mi>M</mml:mi><mml:mn>2</mml:mn></mml:msup><mml:mo>)</mml:mo></mml:mrow></mml:math><inline-graphic xlink:href="qiu-ieq1-3150403.gif"/> </inline-formula> time, where <inline-formula><tex-math notation="LaTeX">N</tex-math> <mml:math><mml:mi>N</mml:mi></mml:math><inline-graphic xlink:href="qiu-ieq2-3150403.gif"/> </inline-formula> denotes the dataset size and <inline-formula><tex-math notation="LaTeX">M</tex-math> <mml:math><mml:mi>M</mml:mi></mml:math><inline-graphic xlink:href="qiu-ieq3-3150403.gif"/> </inline-formula> is an intermediate variable denoting the number of local density peaks. As our experimental results reveal, when processing large-size datasets, the value of <inline-formula><tex-math notation="LaTeX">M</tex-math> <mml:math><mml:mi>M</mml:mi></mml:math><inline-graphic xlink:href="qiu-ieq4-3150403.gif"/> </inline-formula> could be very large and consequently those steps of LDP-MST involving <inline-formula><tex-math notation="LaTeX">O(M^{2})</tex-math> <mml:math><mml:mrow><mml:mi>O</mml:mi><mml:mo>(</mml:mo><mml:msup><mml:mi>M</mml:mi><mml:mn>2</mml:mn></mml:msup><mml:mo>)</mml:mo></mml:mrow></mml:math><inline-graphic xlink:href="qiu-ieq5-3150403.gif"/> </inline-formula> time term would be time-consuming. And in the worst case, the value of <inline-formula><tex-math notation="LaTeX">M</tex-math> <mml:math><mml:mi>M</mml:mi></mml:math><inline-graphic xlink:href="qiu-ieq6-3150403.gif"/> </inline-formula> could be very close to that of <inline-formula><tex-math notation="LaTeX">N</tex-math> <mml:math><mml:mi>N</mml:mi></mml:math><inline-graphic xlink:href="qiu-ieq7-3150403.gif"/> </inline-formula>, which means that the time complexity of LDP-MST could be <inline-formula><tex-math notation="LaTeX">O(N^{2})</tex-math> <mml:math><mml:mrow><mml:mi>O</mml:mi><mml:mo>(</mml:mo><mml:msup><mml:mi>N</mml:mi><mml:mn>2</mml:mn></mml:msup><mml:mo>)</mml:mo></mml:mrow></mml:math><inline-graphic xlink:href="qiu-ieq8-3150403.gif"/> </inline-formula> in the worst case of <inline-formula><tex-math notation="LaTeX">M</tex-math> <mml:math><mml:mi>M</mml:mi></mml:math><inline-graphic xlink:href="qiu-ieq9-3150403.gif"/> </inline-formula>. In this study, we use more efficient algorithms to implement those steps of LDP-MST that involve the <inline-formula><tex-math notation="LaTeX">O(M^{2})</tex-math> <mml:math><mml:mrow><mml:mi>O</mml:mi><mml:mo>(</mml:mo><mml:msup><mml:mi>M</mml:mi><mml:mn>2</mml:mn></mml:msup><mml:mo>)</mml:mo></mml:mrow></mml:math><inline-graphic xlink:href="qiu-ieq10-3150403.gif"/> </inline-formula> time term such that the proposed method, Fast LDP-MST, has <inline-formula><tex-math notation="LaTeX">O(N\log N)</tex-math> <mml:math><mml:mrow><mml:mi>O</mml:mi><mml:mo>(</mml:mo><mml:mi>N</mml:mi><mml:mo form="prefix">log</mml:mo><mml:mi>N</mml:mi><mml:mo>)</mml:mo></mml:mrow></mml:math><inline-graphic xlink:href="qiu-ieq11-3150403.gif"/> </inline-formula> time complexity even if <inline-formula><tex-math notation="LaTeX">M\approx N</tex-math> <mml:math><mml:mrow><mml:mi>M</mml:mi><mml:mo>≈</mml:mo><mml:mi>N</mml:mi></mml:mrow></mml:math><inline-graphic xlink:href="qiu-ieq12-3150403.gif"/> </inline-formula>. Our experiments demonstrate that Fast LDP-MST is overall more efficient than LDP-MST on large-size datasets, without sacrificing the merits of LDP-MST in effectiveness, robustness, and user-friendliness.
Inspired by biological helices (e.g., DNA), artificial helical polymers have attracted intense attention. However, precise synthesis of one‐handed helices from achiral materials remains a formidable ...challenge. Herein, a series of achiral poly(biphenyl allene)s with controlled molar mass and low dispersity were prepared and induced into one‐handed helices using chiral amines and alcohols. The induced one‐handed helix was simultaneously memorized, even after the chiral inducer was removed. The switchable induction processes were visible to naked eye; the achiral polymers exhibited blue emission (irradiated at 365 nm), whereas the induced one‐handed helices exhibited cyan emission with clear circularly polarized luminescence. The induced helices formed stable gels in various solvents with helicity discrimination ability: the same‐handed helix gels were self‐healing, whereas the gels of opposite‐handed helicity were self‐sorted. Moreover, the induced helices could separate enantiomers via enantioselective crystallization with high efficiency and switchable enantioselectivity.
A family of racemic polymers were induced into one‐handed helices which were memorized after the chiral inducer was removed. The enantiomeric excess of one handed helix (eeh) is up to 98 %. Interestingly, the switchable helix‐induction is visible with the naked eye. Moreover, the one‐handed helices exhibit enhanced stability with helicity discrimination and enantiomer separation abilities.
Summary
Nuclear genomes of two isolates of Hirsutella thompsonii, a pathogen causing epizootics among mites, have been reported; in contrast, its mitochondrial genome (mitogenome) has remained ...unknown, limiting our understanding of its evolution. Herein, we annotated the first complete mitogenome of H. thompsonii, which encoded all standard fungal mitochondrial genes plus three free‐standing ORFs. Transcriptional analyses validated the expression of most conserved genes and revealed some interesting transcription patterns of mitochondrial genes. Phylogenetic analyses confirmed its placement in Ophiocordycipitaceae. Comparison of five different isolates originally collected from different locations revealed mitogenome size variations (60.3–66.4 kb) mainly due to different numbers of introns. A total of 15 intron loci were identified, with 11 existing in all 5 isolates and 4 showing presence/absence dynamics. These introns were most likely obtained through horizontal transfer from other fungal organisms. Those common introns might have been in H. thompsonii mitogenomes since the divergence of the fungus from its putative sister species H. minnesotensis, whereas those dynamic introns might have experienced 1–2 gain or loss events. We also detected evidence of degeneration for some introns. Overall, our study shed new insights into the mitochondrial evolution of the acaropathogenic fungus H. thompsonii.
We propose an underwater image enhancement model inspired by the morphology and function of the teleost fish retina. We aim to solve the problems of underwater image degradation raised by the ...blurring and nonuniform color biasing. In particular, the feedback from color-sensitive horizontal cells to cones and a red channel compensation are used to correct the nonuniform color bias. The center-surround opponent mechanism of the bipolar cells and the feedback from amacrine cells to interplexiform cells then to horizontal cells serve to enhance the edges and contrasts of the output image. The ganglion cells with color-opponent mechanism are used for color enhancement and color correction. Finally, we adopt a luminance-based fusion strategy to reconstruct the enhanced image from the outputs of ON and OFF pathways of fish retina. Our model utilizes the global statistics (i.e., image contrast) to automatically guide the design of each low-level filter, which realizes the self-adaption of the main parameters. Extensive qualitative and quantitative evaluations on various underwater scenes validate the competitive performance of our technique. Our model also significantly improves the accuracy of transmission map estimation and local feature point matching using the underwater image. Our method is a single image approach that does not require the specialized prior about the underwater condition or scene structure.
Non‐small cell lung cancer (NSCLC) with wild‐type epidermal growth factor receptor (EGFR) is intrinsic resistance to EGFR‐tyrosine kinase inhibitors (TKIs), such as afatinib. Celastrol, a natural ...compound with antitumor activity, was reported to induce paraptosis in cancer cells. In this study, intrinsic EGFR‐TKI‐resistant NSCLC cell lines H23 (EGFR wild‐type and KRAS mutation) and H292 (EGFR wild‐type and overexpression) were used to test whether celastrol could overcome primary afatinib resistance through paraptosis induction. The synergistic effect of celastrol and afatinib on survival inhibition of the NSCLC cells was evaluated by CCK‐8 assay and isobologram analysis. The paraptosis and its modulation were assessed by light and electron microscopy, Western blot analysis, and immunofluorescence. Xenografts models were established to investigate the inhibitory effect of celastrol plus afatinib on the growth of the NSCLC tumors in vivo. Results showed that celastrol acted synergistically with afatinib to suppress the survival of H23 and H292 cells by inducing paraptosis characterized by extensive cytoplasmic vacuolation. This process was independent of apoptosis and not associated with autophagy induction. Afatinib plus celastrol‐induced cytoplasmic vacuolation was preceded by endoplasmic reticulum stress and unfolded protein response. Accumulation of intracellular reactive oxygen species and mitochondrial Ca2+ overload may be initiating factors of celastrol/afatinib‐induced paraptosis and subsequent cell death. Furthermore, Celastrol and afatinib synergistically suppressed the growth of H23 cell xenograft tumors in vivo. The data indicate that a combination of afatinib and celastrol may be a promising therapeutic strategy to surmount intrinsic afatinib resistance in NSCLC cells.
Graphical
Celastrol acted synergistically with afatinib to suppress the survival of non‐small cell lung cancer cells by inducing paraptosis.
Afatinib plus celastrol‐induced paraptosis was mediated by endoplasmic reticulum stress and unfolded protein response.
Accumulation of intracellular reactive oxygen species and mitochondrial Ca2+ overload induced by celastrol/afatinib may be an initiating factor of paraptosis and subsequent cell death.
Periodontitis, which progressively destroys tooth-supporting structures, is one of the most widespread infectious diseases and the leading cause of tooth loss in adults. Evidence from preclinical ...trials and small-scale pilot clinical studies indicates that stem cells derived from periodontal ligament tissues are a promising therapy for the regeneration of lost/damaged periodontal tissue. This study assessed the safety and feasibility of using autologous periodontal ligament stem cells (PDLSCs) as an adjuvant to grafting materials in guided tissue regeneration (GTR) to treat periodontal intrabony defects. Our data provide primary clinical evidence for the efficacy of cell transplantation in regenerative dentistry.
We conducted a single-center, randomized trial that used autologous PDLSCs in combination with bovine-derived bone mineral materials to treat periodontal intrabony defects. Enrolled patients were randomly assigned to either the Cell group (treatment with GTR and PDLSC sheets in combination with Bio-oss(®)) or the Control group (treatment with GTR and Bio-oss(®) without stem cells). During a 12-month follow-up study, we evaluated the frequency and extent of adverse events. For the assessment of treatment efficacy, the primary outcome was based on the magnitude of alveolar bone regeneration following the surgical procedure.
A total of 30 periodontitis patients aged 18 to 65 years (48 testing teeth with periodontal intrabony defects) who satisfied our inclusion and exclusion criteria were enrolled in the study and randomly assigned to the Cell group or the Control group. A total of 21 teeth were treated in the Control group and 20 teeth were treated in the Cell group. All patients received surgery and a clinical evaluation. No clinical safety problems that could be attributed to the investigational PDLSCs were identified. Each group showed a significant increase in the alveolar bone height (decrease in the bone-defect depth) over time (p < 0.001). However, no statistically significant differences were detected between the Cell group and the Control group (p > 0.05).
This study demonstrates that using autologous PDLSCs to treat periodontal intrabony defects is safe and does not produce significant adverse effects. The efficacy of cell-based periodontal therapy requires further validation by multicenter, randomized controlled studies with an increased sample size.
NCT01357785 Date registered: 18 May 2011.
Lung adenocarcinoma (LUAD) is characterized by a high incidence rate and mortality. Recently, POC1 centriolar protein A (POC1A) has emerged as a potential biomarker for various cancers, contributing ...to cancer onset and development. However, the association between POC1A and LUAD remains unexplored. We extracted The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) data sets to analyse the differential expression of POC1A and its relationship with clinical stage. Additionally, we performed diagnostic receiver operator characteristic (ROC) curve analysis and Kaplan–Meier (KM) survival analysis to assess the diagnostic and prognostic value of POC1A in LUAD. Furthermore, we investigated the correlation between POC1A expression and immune infiltration, tumour mutation burden (TMB), immune checkpoint expression and drug sensitivity. Finally, we verified POC1A expression using real‐time quantitative polymerase chain reaction (RT‐qPCR) and immunohistochemistry (IHC). Cell experiments were conducted to validate the effect of POC1A expression on the proliferation, migration and invasion of lung cancer cells. POC1A exhibited overexpression in most tumour tissues, and its overexpression in LUAD was significantly correlated with late‐stage presentation and poor prognosis. The high POC1A expression group showed lower levels of immune infiltration but higher levels of immune checkpoint expression and TMB. Moreover, the high POC1A expression group demonstrated sensitivity to multiple drugs. In vitro experiments confirmed that POC1A knockdown led to decreased proliferation, migration, and invasion of lung cancer cells. Our findings suggest that POC1A may contribute to tumour development by modulating the cell cycle and immune cell infiltration. It also represents a potential therapeutic target and marker for the diagnosis and prognosis of LUAD.
Image enhancement is an important pre-processing step for many computer vision applications especially regarding the scenes in poor visibility conditions. In this work, we develop a unified ...two-pathway model inspired by the biological vision, especially the early visual mechanisms, which contributes to image enhancement tasks including low dynamic range (LDR) image enhancement and high dynamic range (HDR) image tone mapping. Firstly, the input image is separated and sent into two visual pathways: structure-pathway and detail-pathway, corresponding to the M- and P-pathway in the early visual system, which code the low- and high-frequency visual information, respectively. In the structure-pathway, an extended biological normalization model is used to integrate the global and local luminance adaptation, which can handle the visual scenes with varying illuminations. On the other hand, the detail enhancement and local noise suppression are achieved in the detail-pathway based on local energy weighting. Finally, the outputs of structure-and detail-pathway are integrated to achieve the low-light image enhancement. In addition, the proposed model can also be used for tone mapping of HDR images with some fine-tuning steps. Extensive experiments on three datasets (two LDR image datasets and one HDR scene dataset) show that the proposed model can handle the visual enhancement tasks mentioned above efficiently and outperform the related state-of-the-art methods.
Cervical cancer is common cancer among women with high morbidity. MicroRNAs (miRs) are involved in the progression and development of cervical cancer. This study aimed to explore the effect of ...miR‐99b‐5p (miR‐99b) on invasion and migration in cervical cancer through the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway. The microarray‐based analysis was used to screen out differentially expressed miRNAs. Expression of miR‐99b, PI3K, AKT, mTOR, and ribosomal protein S6 kinase (p70S6K) was determined in both cervical cancer tissues and paracancerous tissues. Next, alteration of miR‐99b expression in cervical cancer was conducted to evaluate levels of PI3K, AKT, mTOR, p70S6K matrix metallopeptidase 2, epithelial cell adhesion molecule, and intercellular adhesion molecule 1, as well as the effect of miR‐99b on cell proliferation, invasion, migration, cell cycle distribution, and apoptosis. The results demonstrated that miR‐99b expression was decreased and levels of PI3K, AKT, mTOR, and p70S6K were elevated in cervical cancer tissues. More important, overexpressed miR‐99b repressed the PI3K/AKT/mTOR signaling pathway, inhibited cell proliferation, invasion, and migration, blocked cell cycle entry, and promoted apoptosis in cervical cancer. These results indicate that miR‐99b attenuates the migration and invasion of human cervical cancer cells through downregulation of the PI3K/AKT/mTOR signaling pathway, which provides a therapeutic approach for cervical cancer treatment.
These results indicate that miR‐99b attenuates the migration and invasion of human cervical cancer cells through downregulation of the phosphatidylinositol 3‐kinase/protein kinase B/mechanistic target of rapamycin signaling pathway, which provides a therapeutic approach for cervical cancer treatment.
The evaluation of childhood trauma is essential for the treatment of schizophrenia. The short form of Childhood Trauma Questionnaire (CTQ-SF) is a widely used measure of the experience of childhood ...trauma in the general population. Nevertheless, data regarding the psychometric property of CTQ-SF for assessing childhood trauma of patients with schizophrenia are very limited.
Two hundred Chinese inpatients with schizophrenia completed the Chinese CTQ-SF, the Child Psychological Maltreatment Scale (CPMS), the Impact of Events Scale-Revised (IES-R), and the Dissociative Experiences Scale-II (DES-II). To assess test-retest reliability of the CTQ-SF, all patients completed the CTQ-SF again two weeks later. Concurrent and convergent validity was assessed by analyzing Pearson bivariate correlation coefficients between CTQ-SF and CPMS, IES-R, and DES-II.
The Cronbach's α coefficient of the Chinese CTQ-SF was 0.81, and the two-week re-test reliability was 0.81 (P<0.01). The criterion-related validity coefficients of CTQ-SF with the CMPS, IES-R and DES-II were 0.61, 0.41, and 0.51, respectively.
The Chinese CTQ-SF has satisfactory psychometric properties to measure childhood abuse or neglect in Chinese inpatients with schizophrenia.
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