120 research outputs found

    Sparse Signal Inversion with Impulsive Noise by Dual Spectral Projected Gradient Method

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    We consider sparse signal inversion with impulsive noise. There are three major ingredients. The first is regularizing properties; we discuss convergence rate of regularized solutions. The second is devoted to the numerical solutions. It is challenging due to the fact that both fidelity and regularization term lack differentiability. Moreover, for ill-conditioned problems, sparsity regularization is often unstable. We propose a novel dual spectral projected gradient (DSPG) method which combines the dual problem of multiparameter regularization with spectral projection gradient method to solve the nonsmooth l1+l1 optimization functional. We show that one can overcome the nondifferentiability and instability by adding a smooth l2 regularization term to the original optimization functional. The advantage of the proposed functional is that its convex duality reduced to a constraint smooth functional. Moreover, it is stable even for ill-conditioned problems. Spectral projected gradient algorithm is used to compute the minimizers and we prove the convergence. The third is numerical simulation. Some experiments are performed, using compressed sensing and image inpainting, to demonstrate the efficiency of the proposed approach

    Transcriptional control of Flt3 ligand targeted by fluorouracil-induced Egr-1 promoter in hematopoietic damage

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    <p>Abstract</p> <p>Background</p> <p>Ionizing radiation (IR) activate the early growth response-1 (Egr-1) promoter by production of radical oxygen intermediates (ROIs). Egr-EF, an expression vector pCIneo containing Egr-1 promoter cloned upstream of the cDNA for Flt3 ligand, was used to treat hematopoietic damage. 5-fluorouracil, a commonly used chemotherapeutic agent, cause tumor cell death by producing DNA damage and generating ROIs. We therefore hypothesized that clinically employed chemotherapeutic agents that increase ROIs could also be employed to activate Egr-EF in a chemoinducible gene therapy strategy. The goal of this study was to explore the effect of Flt3 Ligand gene transcription regulated by fluorouracil-induced Egr-1 promoter on hematopoietic recovery.</p> <p>Methods</p> <p>Human Flt3 Ligand (FL) cDNA and enhanced green fluorescent protein (EGFP) cDNA were linked together with IRES and inserted into the expression vector pCI-neo under control of the Egr-1 promoter (Egr-EF). The vector was transfected into the HFCL human bone marrow stromal cell line, and these cells were exposed to 5-FU, a chemotherapeutic drug. Expression of FL by HFCL/EF cells after 5-FU treatment was determined with ELISA, western blot and RT-PCR assays. In addition, the effect of FL from HFCL/EF cell culture supernatants on growth of CD34<sup>+ </sup>cells from cord blood was also studied. HFCL/EF cells were injected into CB-17 combined immunodeficient (SCID) mice with B16 melanoma. 5-FU was given three days after injection of the HFCL/EF cells. In the recipient mice, white blood cell levels in peripheral blood and expression of EGFP and FL in human stromal cells were measured. Tumor volumes in tumor-bearing mice were also measured.</p> <p>Results</p> <p>5-FU treatment increased EGFP levels and secreted FL levels in HFCL/EF cells. Supernatants from HFCL/EF cell cultures treated with 5-FU increased CD34<sup>+ </sup>cell growth significantly. HFCL/EF exhibited an increase in the number of white blood cells after chemotherapy.</p> <p>Conclusion</p> <p>The data presented here support the use of transcriptional control mediated by chemoinducible gene therapy to reduce hematopoietic injury associated with 5-FU.</p

    Sound absorption, structure and mechanical behavior of konjac glucomannan-based aerogels with addition of gelatin and wheat straw

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    Environment-friendly konjac glucomannan (KGM)-based aerogels with addition of gelatin and wheat straw are produced by freeze-drying method to have promising sound absorption performance, thermal stability and mechanical property. Results show that gelatin addition can significantly improve sound absorption performance at medium and high frequencies, as well as mechanical strength, because of the positive effect on increase of small open pores. Appropriate little addition of wheat straw can improve the sound absorption property due to the dissipation effect of sound energy by the unique multi-cavity structure. Better sound absorption performance is achieved than melamine foam, while the best result is obtained with a noise reduction coefficient of 0.38, and the coefficient reaches 0.88 at 4500 Hz. Wheat straw addition leads to strength reduction firstly but enhancement when the addition is more than 1.00%, where fine wheat straw bars form nest structures for strengthening. For potential loading capacity evaluation, a mechanical model is proposed and confirmed to be effective in predicting compressive stress-strain relationship of KGM-based aerogels with consideration of gelatin and wheat straw addition

    Retrospective seroepidemiology indicated that human enterovirus 71 and coxsackievirus A16 circulated wildly in central and southern China before large-scale outbreaks from 2008

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    <p>Abstract</p> <p>Background</p> <p>Large nationwide outbreaks of hand, foot, and mouth disease (HFMD) occurred in China from 2008; most of the cases were in children under 5 years. This study aims to identify the situation of natural human enterovirus 71 (HEV71) and coxsackievirus A16 (CVA16) infections in children before 2008 in China.</p> <p>Results</p> <p>Retrospective seroepidemiologic studies of HEV71 and CVA16 were performed with 900 serum samples collected from children ≤5 years of age in 2005. The samples were collected from 6 different geographical areas (Anhui, Guangdong, Hunan, Xinjiang, Yunnan, and Heilongjiang provinces) in mainland China. Of the 900 samples, 288 were positive for HEV71; the total positive rate was 32.0% and the geometric mean titer (GMT) was 1:8.5. Guangdong (43.7% and 1:10.8), Xinjiang (45.4% and 1:11.1), and Yunnan (43.4% and 1:12.0) provinces had relatively high rates of infection, while Heilongjiang province (8.1% and 1:4.9) had the lowest rate of infection. On the other hand, 390 samples were positive for CVA16; the total positive rate was 43.4% and the GMT was 1:9.5. Anhui (62.2% and 1:16.0) and Hunan (61.1% and 1:23.1) had relatively high rates, while Heilongjiang (8.0% and 1:4.6) had the lowest rate. Although there is a geographical difference in HEV71 and CVA16 infections, low neutralizing antibody positive rate and titer of both viruses were found in all 6 provinces.</p> <p>Conclusions</p> <p>This report confirmed that HEV71 and CVA16 had wildly circulated in a couple provinces in China before the large-scale outbreaks from 2008. This finding also suggests that public health measures to control the spread of HEV71 and CVA16 should be devised according to the different regional characteristics.</p

    Global supply chains amplify economic costs of future extreme heat risk

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    Evidence shows a continuing increase in the frequency and severity of global heatwaves, raising concerns about the future impacts of climate change and the associated socioeconomic costs. Here we develop a disaster footprint analytical framework by integrating climate, epidemiological and hybrid input–output and computable general equilibrium global trade models to estimate the midcentury socioeconomic impacts of heat stress. We consider health costs related to heat exposure, the value of heat-induced labour productivity loss and indirect losses due to economic disruptions cascading through supply chains. Here we show that the global annual incremental gross domestic product loss increases exponentially from 0.03 ± 0.01 (SSP 245)–0.05 ± 0.03 (SSP 585) percentage points during 2030–2040 to 0.05 ± 0.01–0.15 ± 0.04 percentage points during 2050–2060. By 2060, the expected global economic losses reach a total of 0.6–4.6% with losses attributed to health loss (37–45%), labour productivity loss (18–37%) and indirect loss (12–43%) under different shared socioeconomic pathways. Small- and medium-sized developing countries suffer disproportionately from higher health loss in South-Central Africa (2.1 to 4.0 times above global average) and labour productivity loss in West Africa and Southeast Asia (2.0–3.3 times above global average). The supply-chain disruption effects are much more widespread with strong hit to those manufacturing-heavy countries such as China and the USA, leading to soaring economic losses of 2.7 ± 0.7% and 1.8 ± 0.5%, respectively.

    Molecular mechanisms of pruritus in prurigo nodularis

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    Pruritus is the most common symptom of dermatological disorders, and prurigo nodularis (PN) is notorious for intractable and severe itching. Conventional treatments often yield disappointing outcomes, significantly affecting patients’ quality of life and psychological well-being. The pathogenesis of PN is associated with a self-sustained “itch-scratch” vicious cycle. Recent investigations of PN-related itch have partially revealed the intricate interactions within the cutaneous neuroimmune network; however, the underlying mechanism remains undetermined. Itch mediators play a key role in pruritus amplification in PN and understanding their action mechanism will undoubtedly lead to the development of novel targeted antipruritic agents. In this review, we describe a series of pruritogens and receptors involved in mediating itching in PN, including cytokines, neuropeptides, extracellular matrix proteins, vasculogenic substances, ion channels, and intracellular signaling pathways. Moreover, we provide a prospective outlook on potential therapies based on existing findings

    Research progress of 3D printed poly (ether ether ketone) in the reconstruction of craniomaxillofacial bone defects

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    The clinical challenge of bone defects in the craniomaxillofacial region, which can lead to significant physiological dysfunction and psychological distress, persists due to the complex and unique anatomy of craniomaxillofacial bones. These critical-sized defects require the use of bone grafts or substitutes for effective reconstruction. However, current biomaterials and methods have specific limitations in meeting the clinical demands for structural reinforcement, mechanical support, exceptional biological performance, and aesthetically pleasing reconstruction of the facial structure. These drawbacks have led to a growing need for novel materials and technologies. The growing development of 3D printing can offer significant advantages to address these issues, as demonstrated by the fabrication of patient-specific bioactive constructs with controlled structural design for complex bone defects in medical applications using this technology. Poly (ether ether ketone) (PEEK), among a number of materials used, is gaining recognition as a feasible substitute for a customized structure that closely resembles natural bone. It has proven to be an excellent, conformable, and 3D-printable material with the potential to replace traditional autografts and titanium implants. However, its biological inertness poses certain limitations. Therefore, this review summarizes the distinctive features of craniomaxillofacial bones and current methods for bone reconstruction, and then focuses on the increasingly applied 3D printed PEEK constructs in this field and an update on the advanced modifications for improved mechanical properties, biological performance, and antibacterial capacity. Exploring the potential of 3D printed PEEK is expected to lead to more cost-effective, biocompatible, and personalized treatment of craniomaxillofacial bone defects in clinical applications

    Retinal alterations in evaluation of rheumatoid arthritis with chloroquine treatment: A new approach

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    Objective: To evaluate the effect of hydroxychloroquine on conjunctival and retinal microvascular density in rheumatoid arthritis (RA) patients. Methods: Ten healthy controls, 10 RA patients who had not been treated with hydroxychloroquine, and 10 RA patients who had been treated with chloroquine for more than 5 years were recruited. Optical coherence tomography (OCTA) was used to examine the conjunctival and superficial and deep retinal microvascular density and compared the differences in microvascular density between the three groups. Results: The vascular density in RA group in superficial microvascular was significantly lower than that in control group (p < 0.001). Compared with RA group, the chloroquine group showed statistically significantly lower microvascular (p < 0.001) and deep microvascular (p = 0.018). Superficial microvascular was positively correlated with conjunctival vessel density in RA patients (r = 0.868, p = 0.0048). Conclusions: The use of chloroquine could further reduce the vascular density in the absence of statistical difference in the course of the disease

    Ubiquitin ligase RNF125 targets PD-L1 for ubiquitination and degradation

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    As a critical immune checkpoint molecule, PD-L1 is expressed at significantly higher levels in multiple neoplastic tissues compared to normal ones. PD-L1/PD-1 axis is a critical target for tumor immunotherapy, blocking the PD-L1/PD-1 axis is recognized and has achieved unprecedented success in clinical applications. However, the clinical efficacy of therapies targeting the PD-1/PD-L1 pathway remains limited, emphasizing the need for the mechanistic elucidation of PD-1/PD-L1 expression. In this study, we found that RNF125 interacted with PD-L1 and regulated PD-L1 protein expression. Mechanistically, RNF125 promoted K48-linked polyubiquitination of PD-L1 and mediated its degradation. Notably, MC-38 and H22 cell lines with RNF125 knockout, transplanted in C57BL/6 mice, exhibited a higher PD-L1 level and faster tumor growth than their parental cell lines. In contrast, overexpression of RNF125 in MC-38 and H22 cells had the opposite effect, resulting in lower PD-L1 levels and delayed tumor growth compared with parental cell lines. In addition, immunohistochemical analysis of MC-38 tumors with RNF125 overexpression showed significantly increased infiltration of CD4+, CD8+ T cells and macrophages. Consistent with these findings, analyses using The Cancer Genome Atlas (TCGA) public database revealed a positive correlation of RNF125 expression with CD4+, CD8+ T cell and macrophage tumor infiltration. Moreover, RNF125 expression was significantly downregulated in several human cancer tissues, and was negatively correlated with the clinical stage of these tumors, and patients with higher RNF125 expression had better clinical outcomes. Our findings identify a novel mechanism for regulating PD-L1 expression and may provide a new strategy to increase the efficacy of immunotherapy

    Effect of sarcopenia on survival of patients with cirrhosis: A meta-analysis

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    The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, by sex, underlying liver disease etiology, and severity of hepatic dysfunction.PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with additional manual search of bibliographies of relevant articles. Cohort studies of ?100 patients with cirrhosis and ?12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included.22 studies with 6965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), higher in male patients, patients with alcohol associated liver disease (ALD), patients with CTP grade C, and when sarcopenia was defined in patients by lumbar 3- skeletal muscle index (L3-SMI). Sarcopenia was associated with the increased risk of mortality in patients with cirrhosis (adjusted-hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in sensitivity analysis of cirrhosis patients without HCC (aHR 2.35, 95% CI 1.95-2.83) and in subgroup analysis by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the poor prognosis for patients with sarcopenia (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in all analyses.Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis.The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% in patients with ALD or Child's class C cirrhosis. Sarcopenia was independently associated with about 2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer period of having sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized
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