Content-sensitive superpixel generation with boundary adjustment.

Superpixel segmentation has become a crucial tool in many image processing and computer vision applications. In this paper, a novel content-sensitive superpixel generation algorithm with boundary adjustment is proposed. First, the image local entropy was used to measure the amount of information in the image, and the amount of information was evenly distributed to each seed. It placed more seeds to achieve the lower under-segmentation in content-dense regions, and placed the fewer seeds to increase computational efficiency in content-sparse regions. Second, the Prim algorithm was adopted to generate uniform superpixels efficiently. Third, a boundary adjustment strategy with the adaptive distance further optimized the superpixels to improve the performance of the superpixel. Experimental results on the Berkeley Segmentation Database show that our method outperforms competing methods under evaluation metrics

Orca-010, a Novel Potency-enhanced Oncolytic Adenovirus, Exerts Strong Antitumor Activity in Preclinical Models

Improving the antitumor potency of current oncolytic adenoviruses represents one of the major challenges in development of these viruses for clinical use. We have generated an oncolytic adenovirus carrying the safety-enhancing E1A Delta 24 deletion, the potency-enhancing T1 mutation, and the infectivity-enhancing fiber RGD modification. The results of in vitro cytotoxicity assays on 15 human cancer cell lines derived from different tumor types demonstrated that ORCA-010 is more potent than Ad5-Delta 24RGD or ONYX-015. As ORCA-010 will initially be developed for the treatment of prostate cancer, selectivity experiments were performed using primary human prostate cells. ORCA-010 killed cancer cells more effectively than these primary human cells. In both primary prostate fibroblasts and epithelial cells, ORCA-010 was as safe as Ad5-Delta 24RGD. Evaluation of ORCA-010 in in vivo xenograft tumor models in nude mice showed that ORCA-010 significantly inhibited growth of prostate, lung, and ovarian tumors and conferred prolonged survival of tumor-bearing animals. Furthermore, we observed a substantial increase in infectious viral particles in tumors injected with ORCA-010. The number of infectious viral particles increased after treatment and infectious particles remained present up to at least 4 weeks posttreatment. Intratumoral virus replication was associated with substantial necrosis and fibrosis. In conclusion, ORCA-010 is more potent than earlier generation oncolytic adenoviruses, without demonstrating increased toxicity. ORCA-010 exerted strong in vivo antitumor activity and is therefore a suitable candidate for clinical evaluation

Ex vivo mono-ring technique simplifies culotte stenting for treatment of true bifurcation lesions: Insights from bench testing and clinical application

Background: Despite various culotte-based stenting techniques available clinically, the optimal one remains undetermined. The study aimed to test whether ex vivo mono-ring culotte stenting (MRC) was technically feasible and superior to mini culotte stenting (MCS) in treatment of coronary bifurcation lesions.Methods: Mono-ring culotte stenting was characterized by ex vivo wiring of the most proximal cell of the side branch (SB) stent to ensure a mono-ring result of the culotte stenting. Comparison of MRC vs. MCS in treatment of true bifurcation lesions was performed in vitro (n = 15 for each group) and in clinical case-controlled study with propensity matching at a ratio of 1:2 (n = 21 for MRC group; n = 42 for MCS group).Results: Compared to MCS, MRC had lower incidence of stent under-expansion band (0% vs. 53.3%, p = 0.002) and less residual ostial area stenosis of SB (9.2 ± 9.0% vs. 20.0 ± 14.8%, p = 0.023), as assessed in vitro by micro-computed tomography. In a case-controlled study, no adverse cardiac events were observed in the MRC group. The procedural success was similar between MRC and MCS (100% vs. 95.2%, p = 0.548), but MRC had less residual ostial stenosis of the SB (8.7% ± 11.0% vs. 16.8% ± 11.2%, p = 0.008), lower procedural(33.3 ± 9.5 min vs. 46.7 ± 15.6 min, p = 0.001) and fluoroscopic (19.7 ± 4.9 min vs. 26.2 ± 7.1 min, p < 0.001) time, and less contrast use (114.3 ± 28.9 mL vs. 156.5 ± 56.4 mL, p = 0.002).Conclusions: Mono-ring culotte stenting as compared to MCS is associated with better bifurcation stent morphology,less procedural complexity and residual ostial SB stenosis

Effectiveness and safety of anti-BCMA chimeric antigen receptor T-cell treatment in relapsed/refractory multiple myeloma: a comprehensive review and meta-analysis of prospective clinical trials

Background: Chimeric antigen receptor T cells treatment targeting B cell maturation antigen (BCMA) is an emerging treatment option for relapsed/refractory multiple myeloma (RRMM) and has demonstrated outstanding outcomes in clinical studies.Objective: The aim of this comprehensive review and meta-analysis was to summarize the effectiveness and safety of anti-BCMA CAR-T treatment for patients with relapsed/refractory multiple myeloma (RRMM). Our research identifies variables influencing outcome measures to provide additional evidence for CAR-T product updates, clinical trial design, and clinical treatment guidance.Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard was followed for conducting this comprehensive review and meta-analysis, which was submitted to PROSPERO (CRD42023390037). From the inception of the study until 10 September 2022, PubMed, Web of Science, EMBASE, the Cochrane Library, CNKI, and WanFang databases were searched for eligible studies. Stata software (version 16.0) was used to assess effectiveness and safety outcomes.Results: Out of 875 papers, we found 21 relevant trials with 761 patients diagnosed as RRMM and were given anti-BCMA CAR-T treatment. The overall response rate (ORR) for the entire sample was 87% (95% CI: 80–93%) complete response rate (CRR) was 44% (95% CI: 34–54%). The minimal residual disease (MRD) negativity rate within responders was 78% (95% CI: 65–89%). The combined incidence of cytokine release syndrome was 82% (95% CI: 72–91%) and neurotoxicity was 10% (95% CI: 5%–17%). The median progression-free survival (PFS) was 8.77 months (95% CI: 7.48–10.06), the median overall survival (OS) was 18.87 months (95% CI: 17.20–20.54) and the median duration of response (DOR) was 10.32 months (95% CI: 9.34–11.31).Conclusion: According to this meta-analysis, RRMM patients who received anti-BCMA CAR-T treatment have demonstrated both effectiveness and safety. Subgroup analysis confirmed the anticipated inter-study heterogeneity and pinpointed potential factors contributing to safety and efficacy, which may help with the development of CAR-T cell studies and lead to optimized BCMA CAR-T-cell products.Systematic Review Registration:Clinicaltrials.gov, PROSPERO, CRD42023390037

Superconductivity in a new layered cobalt oxychalcogenide Na6_{6}Co3_{3}Se6_{6}O3_{3} with a 3d5d^{5} triangular lattice

Unconventional superconductivity in bulk materials under ambient pressure is extremely rare among the 3$d$ transition-metal compounds outside the layered cuprates and iron-based family. It is predominantly linked to highly anisotropic electronic properties and quasi-two-dimensional (2D) Fermi surfaces. To date, the only known example of the Co-based exotic superconductor was the hydrated layered cobaltate, Na$_{x}$CoO$_{2}\cdot$ yH$_{2}$O, and its superconductivity is realized in the vicinity of a spin-1/2 Mott state. However, the nature of the superconductivity in these materials is still an active subject of debate, and therefore, finding new class of superconductors will help unravel the mysteries of their unconventional superconductivity. Here we report the discovery of unconventional superconductivity at $\sim$ 6.3 K in our newly synthesized layered compound Na$_{6}$Co$_{3}$Se$_{6}$O$_{3}$, in which the edge-shared CoSe$_{6}$ octahedra form [CoSe$_{2}$] layers with a perfect triangular lattice of Co ions. It is the first 3$d$ transition-metal oxychalcogenide superconductor with distinct structural and chemical characteristics. Despite its relatively low $T_{c}$, material exhibits extremely high superconducting upper critical fields, $\mu_{0}H_{c2}(0)$, which far exceeds the Pauli paramagnetic limit by a factor of 3 - 4. First-principles calculations show that Na$_{6}$Co$_{3}$Se$_{6}$O$_{3}$ is a rare example of negative charge transfer superconductor. This new cobalt oxychalcogenide with a geometrical frustration among Co spins, shows great potential as a highly appealing candidate for the realization of high-$T_{c}$ and/or unconventional superconductivity beyond the well-established Cu- and Fe-based superconductor families, and opened a new field in physics and chemistry of low-dimensional superconductors

Oncolytic Adenovirus ORCA-010 Activates Proinflammatory Myeloid Cells and Facilitates T Cell Recruitment and Activation by PD-1 Blockade in Melanoma

Immune checkpoint inhibitors have advanced the treatment of melanoma. Nevertheless, a majority of patients are resistant, or develop resistance, to immune checkpoint blockade, which may be related to prevailing immune suppression by myeloid regulatory cells in the tumor microenvironment (TME). ORCA-010 is a novel oncolytic adenovirus that selectively replicates in, and lyses, cancer cells. We previously showed that ORCA-010 can activate melanoma-exposed conventional dendritic cells (cDCs). To study the effect of ORCA-010 on melanoma-conditioned macrophage development, we used an in vitro co-culture model of human monocytes with melanoma cell lines. We observed a selective survival and polarization of monocytes into M2-like macrophages (CD14(+)CD80(-)CD163(+)) in co-cultures with cell lines that expressed macrophage colony-stimulating factor. Oncolysis of these melanoma cell lines, effected by ORCA-010, activated the resulting macrophages and converted them to a more proinflammatory state, evidenced by higher levels of PD-L1, CD80, and CD86 and an enhanced capacity to prime allogenic T cells and induce a type-1 T cell response. To assess the effect of ORCA-010 on myeloid subset distribution and activation in vivo, ORCA-010 was intratumorally injected and tested for T cell activation and recruitment in the human adenovirus nonpermissive B16-OVA mouse melanoma model. While systemic PD-1 blockade in this model in itself did not modulate myeloid or T cell subset distribution and activation, when it was preceded by i.t. injection of ORCA-010, this induced an increased rate and activation state of CD8 alpha(+) cDC1, both in the TME and in the spleen. Observed increased rates of activated CD8(+) T cells, expressing CD69 and PD-1, were related to both increased CD8 alpha(+) cDC1 rates and M1/M2 shifts in tumor and spleen. In conclusion, the myeloid modulatory properties of ORCA-010 in melanoma, resulting in recruitment and activation of T cells, could enhance the antitumor efficacy of PD-1 blockade.Peer reviewe

Integrated Network Pharmacology and Metabolomics Analysis of the Therapeutic Effects of Zi Dian Fang on Immune Thrombocytopenic Purpura

Current hormone-based treatments for immune thrombocytopenic purpura (ITP) are associated with potentially serious adverse reactions. Zi Dian Fang (ZDF) is a multi-target Traditional Chinese Medicine (TCM) used to treat both the symptoms and root causes of ITP, with fewer side effects than hormone-based treatments. This study analysis of the therapeutic effects of ZDF on ITP from three aspects: platelet proliferation, immunoregulation, and inflammation. After detection of 52 chemical constituents of ZDF by UPLC-Q-TOF/MS, The main targets and pathways affected by ZDF were screened by network pharmacology and verified by Western blot and ELISA. Meanwhile, metabolomics analysis were applied to a mouse model of ITP to identify and screen endogenous terminal metabolites differentially regulated by ZDF. Integrated network pharmacology and metabolomics analysis of the therapeutic effects of ZDF on ITP may be as follows: ZDF counteracts ITP symptoms mainly by inhibiting Ras/MAPKs (Ras/Mitogen-activated protein kinases) pathway, and the expression of upstream protein (Ras) and downstream protein (p-ERK, p-JNK, p-p38) were inhibited, which affects the content of effect index associated with proliferation (Thrombopoietin, TPO; Granulocyte-macrophage colony stimulating factor, GM-CSF), inflammation (Tumor necrosis factor-α, TNF-α; Interleukin-6, IL-6), immune (Interleukin-2, IL-2; Interferon-gamma, IFN-γ; Interleukin-4, IL-4), so that the body’s arginine, Δ12-prostaglandin j2 (Δ12-PGJ2), 9-cis-Retinoic Acid, sphingosine-1-phosphate (S1P), oleic acid amide and other 12 endogenous metabolites significantly changes. Considering the established safety profile, the present study suggests ZDF may be a useful alternative to hormone-based therapies for the treatment of ITP

Iron induces two distinct Ca²⁺ signalling cascades in astrocytes.

From Europe PMC via Jisc Publications RouterHistory: ppub 2021-05-01, epub 2021-05-05Publication status: PublishedFunder: National Natural Science Foundation of China (National Science Foundation of China); Grant(s): 81871852Iron is the fundamental element for numerous physiological functions. Plasmalemmal divalent metal ion transporter 1 (DMT1) is responsible for cellular uptake of ferrous (Fe2+), whereas transferrin receptors (TFR) carry transferrin (TF)-bound ferric (Fe3+). In this study we performed detailed analysis of the action of Fe ions on cytoplasmic free calcium ion concentration ([Ca2+]i) in astrocytes. Administration of Fe2+ or Fe3+ in μM concentrations evoked [Ca2+]i in astrocytes in vitro and in vivo. Iron ions trigger increase in [Ca2+]i through two distinct molecular cascades. Uptake of Fe2+ by DMT1 inhibits astroglial Na+-K+-ATPase, which leads to elevation in cytoplasmic Na+ concentration, thus reversing Na+/Ca2+ exchanger and thereby generating Ca2+ influx. Uptake of Fe3+ by TF-TFR stimulates phospholipase C to produce inositol 1,4,5-trisphosphate (InsP3), thus triggering InsP3 receptor-mediated Ca2+ release from endoplasmic reticulum. In summary, these findings reveal the mechanisms of iron-induced astrocytic signalling operational in conditions of iron overload

Reference genome of wild goat (<i>capra aegagrus</i>) and sequencing of goat breeds provide insight into genic basis of goat domestication

BACKGROUND: Domestic goats (Capra hircus) have been selected to play an essential role in agricultural production systems, since being domesticated from their wild progenitor, bezoar (Capra aegagrus). A detailed understanding of the genetic consequences imparted by the domestication process remains a key goal of evolutionary genomics. RESULTS: We constructed the reference genome of bezoar and sequenced representative breeds of domestic goats to search for genomic changes that likely have accompanied goat domestication and breed formation. Thirteen copy number variation genes associated with coat color were identified in domestic goats, among which ASIP gene duplication contributes to the generation of light coat-color phenotype in domestic goats. Analysis of rapidly evolving genes identified genic changes underlying behavior-related traits, immune response and production-related traits. CONCLUSION: Based on the comparison studies of copy number variation genes and rapidly evolving genes between wild and domestic goat, our findings and methodology shed light on the genetic mechanism of animal domestication and will facilitate future goat breeding. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1606-1) contains supplementary material, which is available to authorized users

Analysis of the dermatophyte Trichophyton rubrum expressed sequence tags

BACKGROUND: Dermatophytes are the primary causative agent of dermatophytoses, a disease that affects billions of individuals worldwide. Trichophyton rubrum is the most common of the superficial fungi. Although T. rubrum is a recognized pathogen for humans, little is known about how its transcriptional pattern is related to development of the fungus and establishment of disease. It is therefore necessary to identify genes whose expression is relevant to growth, metabolism and virulence of T. rubrum. RESULTS: We generated 10 cDNA libraries covering nearly the entire growth phase and used them to isolate 11,085 unique expressed sequence tags (ESTs), including 3,816 contigs and 7,269 singletons. Comparisons with the GenBank non-redundant (NR) protein database revealed putative functions or matched homologs from other organisms for 7,764 (70%) of the ESTs. The remaining 3,321 (30%) of ESTs were only weakly similar or not similar to known sequences, suggesting that these ESTs represent novel genes. CONCLUSION: The present data provide a comprehensive view of fungal physiological processes including metabolism, sexual and asexual growth cycles, signal transduction and pathogenic mechanisms