Existence of positive solutions for singular boundary value problem on time scales

AbstractThis paper deals with a class of boundary value problem of singular differential equations on time scales. The conditions we used here differ from those in the majority of papers as we know. An existence theorem of positive solutions is established by using the Krasnosel'skii fixed point theorem and an example is given to illustrate it

Gab1 and SHP-2 promote Ras/MAPK regulation of epidermal growth and differentiation

În epidermis, Ras can influence proliferation and differentiation; however, regulators of epidermal Ras function are not fully characterized, and Ras effects on growth and differentiation are controversial. EGF induced Ras activation in epidermal cells along with phosphorylation of the multisubstrate docking protein Gab1 and its binding to SHP-2. Expression of mutant Gab1Y627F deficient in SHP-2 binding or dominant-negative SHP-2C459S reduced basal levels of active Ras and downstream MAPK proteins and initiated differentiation. Differentiation triggered by both Gab1Y627F and SHP-2C459S could be blocked by coexpression of active Ras, consistent with Gab1 and SHP-2 action upstream of Ras in this process. To study the role of Gab1 and SHP-2 in tissue, we generated human epidermis overexpressing active Gab1 and SHP-2. Both proteins stimulated proliferation. In contrast, Gab1Y627F and SHP-2C459S inhibited epidermal proliferation and enhanced differentiation. Consistent with a role for Gab1 and SHP-2 in sustaining epidermal Ras/MAPK activity, Gab1−/− murine epidermis displayed lower levels of active Ras and MAPK with postnatal Gab1−/− epidermis, demonstrating the hypoplasia and enhanced differentiation seen previously with transgenic epidermal Ras blockade. These data provide support for a Ras role in promoting epidermal proliferation and opposing differentiation and indicate that Gab1 and SHP-2 promote the undifferentiated epidermal cell state by facilitating Ras/MAPK signaling

Multiple Positive Periodic Solutions for Delay Differential System

We obtain some existence results for multiple positive periodic solutions of some delay differential systems. Examples are presented as applications. For a general positive integer m≥2, main results of this paper do not appear in former literatures as we know. Comparing with the existing results, our results are new also when m=1

Coarse-Super-Resolution-Fine Network (CoSF-Net): A Unified End-to-End Neural Network for 4D-MRI with Simultaneous Motion Estimation and Super-Resolution

Four-dimensional magnetic resonance imaging (4D-MRI) is an emerging technique for tumor motion management in image-guided radiation therapy (IGRT). However, current 4D-MRI suffers from low spatial resolution and strong motion artifacts owing to the long acquisition time and patients' respiratory variations; these limitations, if not managed properly, can adversely affect treatment planning and delivery in IGRT. Herein, we developed a novel deep learning framework called the coarse-super-resolution-fine network (CoSF-Net) to achieve simultaneous motion estimation and super-resolution in a unified model. We designed CoSF-Net by fully excavating the inherent properties of 4D-MRI, with consideration of limited and imperfectly matched training datasets. We conducted extensive experiments on multiple real patient datasets to verify the feasibility and robustness of the developed network. Compared with existing networks and three state-of-the-art conventional algorithms, CoSF-Net not only accurately estimated the deformable vector fields between the respiratory phases of 4D-MRI but also simultaneously improved the spatial resolution of 4D-MRI with enhanced anatomic features, yielding 4D-MR images with high spatiotemporal resolution

Intratumoral Cancer Chemotherapy with a Carrier-Based Immunogenic Cell-Death Eliciting Platinum (IV) Agent

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see doi.org/10.1021/acs.molpharmaceut.0c00781.A carrier-based, immunogenic cell death (ICD)-eliciting platinum(IV) chemotherapeutic agent was synthesized via complexation between an axially derivatized Pt(IV)-tocopherol and hyaluronan (HA)–tocopherol nanocarrier. The resultant HA-Pt(IV) complex demonstrated antiproliferative activity and induced calreticulin translocation, an indicator of ICD, in murine and human head and neck cancer (HNC) cells. The intratumorally administered HA-Pt(IV) treatments were tolerable and efficacious in both immunocompetent and immunodeficient mice with HNC, partially because of the direct cytotoxicity. Superior efficacy and survival were observed in the immunocompetent group, suggesting a possible Pt(IV)-induced immunological response, which would only manifest in animals with an intact immune system. Subsequent imaging of tumor tissues demonstrated increased macrophage infiltration in the HA-Pt(IV)-treated tumors compared to the nontreated controls and the cisplatin-treated tumors, suggesting favorable inflammatory activation. RNA sequencing of HA-Pt(IV)-treated tumors indicated that carbohydrate and vitamin metabolisms were the most important Kyoto Encyclopedia of Genes and Genomes pathways, and molecular function, biological process, and cellular component were highly enriched gene ontology categories

Protective Effect of Antioxidant Peptides Derived from Yak Milk Casein on Oxidative Stress Injury in HEK293 Cells

In this experiment, HEK293 cells were induced by H2O2 to establish a cell model of oxidative damage, and the optimal H2O2 concentration and treatment time were determined. The effects of five antioxidant peptides (AFK, IEQI, FPFF, LPVPQ and RELEEL) derived from yak milk casein on the survival rate, malondialdehyde (MDA) content, antioxidant enzyme activities, reduced glutathione and oxidized glutathione contents of the damaged cells were studied, and the mechanism of action of the antioxidant peptides was explored to provide a theoretical basis for their development and application in high value-added biological products and functional foods. The results showed that these antioxidant peptides had different scavenging effects on different radical species, but they all showed a dose-effect relationship. After being treated with a final concentration of 400 μmol/L H2O2 for 12 h, the inhibitory rate of HEK293 cells was (46.21 ± 0.40)%. Cytotoxicity test showed that the five antioxidant peptides had no toxic or side effects on HEK-293 cells, and did not promote cell proliferation either. These antioxidant peptides could significantly reduce the contents of malondialdehyde (except LPVPQ) and oxidized glutathione in HEK293 cells damaged by oxidation, and enhance the activity of antioxidant enzymes. RELEEL at a concentration of 200 μg/mL significantly reduced MDA content to (0.062 ± 0.000) nmol/104 cells and increased glutathione content to (61.17 ± 2.48) μg/106 cells while maintaining high GSH/GSSG ratio of 64.93 ± 0.95. The antioxidant peptide LPVPQ at 200 μg/mL significantly reduced the content of oxidized glutathione to (0.74 ± 0.26) μg/106 cells and increased the activity of superoxide dismutase (SOD) to (1.17 ± 0.02) U/104 cells; the antioxidant peptide AFK at 200 μg/mL significantly enhanced catalase (CAT) activity to (0.60 ± 0.09) U/104 cells. These results indicate that the antioxidant peptides derived from yak milk casein have positive effects on cells damaged by oxidation, which can provide a reference for further development of relevant products

Bilateral Habenula deep brain stimulation for treatment-resistant depression: clinical findings and electrophysiological features.

Deep brain stimulation (DBS) of structures in the brain's reward system is a promising therapeutic option for patients with treatment-resistant depression (TRD). Recently, DBS of the habenula (HB) in the brain's anti-reward system has also been reported to alleviate depressive symptoms in patients with TRD or bipolar disorder (BD). In this pilot open-label prospective study, we explored the safety and clinical effectiveness of HB-DBS treatment in seven patients with TRD or BD. Also, local field potentials (LFPs) were recorded from the patients' left and right HB to explore the power and asymmetry of oscillatory activities as putative biomarkers of the underlying disease state. At 1-month follow-up (FU), depression and anxiety symptoms were both reduced by 49% (n = 7) along with substantial improvements in patients' health status, functional impairment, and quality of life. Although the dropout rate was high and large variability in clinical response existed, clinical improvements were generally maintained throughout the study [56%, 46%, and 64% reduction for depression and 61%, 48%, and 70% reduction for anxiety at 3-month FU (n = 5), 6-month FU (n = 5), and 12-month FU (n = 3), respectively]. After HB-DBS surgery, sustained improvements in mania symptoms were found in two patients who presented with mild hypomania at baseline. Another patient, however, experienced an acute manic episode 2 months after surgery that required hospitalization. Additionally, weaker and more symmetrical HB LFP oscillatory activities were associated with more severe depression and anxiety symptoms at baseline, in keeping with the hypothesis that HB dysfunction contributes to MDD pathophysiology. These preliminary findings indicate that HB-DBS may offer a valuable treatment option for depressive symptoms in patients who suffer from TRD or BD. Larger and well-controlled studies are warranted to examine the safety and efficacy of HB-DBS for treatment-refractory mood disorders in a more rigorous fashion

Development of Chinese food picture library for inducing food cravings

Cue-induced food cravings are strong desires directed toward specific foods, usually ones with high caloric content, and can lead to overeating. However, although food cravings vary according to individual preferences for specific high-calorie food subtypes, a structured library of food craving-inducing pictures including multiple categories of high-calorie foods does not yet exist. Here, we developed and validated a picture library of Chinese foods (PLCF) consisting of five subtypes of high-calorie foods (i.e., sweets, starches, salty foods, fatty foods, and sugary drinks) to allow for more nuanced future investigations in food craving research, particularly in Chinese cultural contexts. We collected 100 food images representing these five subtypes, with four food items per subtype depicted in five high-resolution photographs each. We recruited 241 individuals with overweight or obesity to rate the food pictures based on craving, familiarity, valence, and arousal dimensions. Of these participants, 213 reported the severity of problematic eating behaviors as a clinical characteristic. Under the condition of mixing multiple subtypes of high-calorie foods, we did not observe significant differences in craving ratings for high- and low-calorie food images (ptukey > 0.05). Then, we compared each subtype of high-calorie food images to low-calorie ones, and found craving ratings were greater for the images of salty foods and sugary drinks (ps < 0.05). Furthermore, we conducted a subgroup analysis of individuals according to whether they did or did not meet the criteria for food addiction (FA) and found that greater cravings induced by the images of high-calorie food subtypes (i.e., salty foods and sugary drinks) only appeared in the subgroup that met the FA criteria. The results show that the PLCF is practical for investigating food cravings

Complete chloroplast genome sequence of Holoparasite Cistanche Deserticola (Orobanchaceae) reveals gene loss and horizontal gene transfer from Its host Haloxylon Ammodendron (Chenopodiaceae)

The central function of chloroplasts is to carry out photosynthesis, and its gene content and structure are highly conserved across land plants. Parasitic plants, which have reduced photosynthetic ability, suffer gene losses from the chloroplast (cp) genome accompanied by the relaxation of selective constraints. Compared with the rapid rise in the number of cp genome sequences of photosynthetic organisms, there are limited data sets from parasitic plants. The authors report the complete sequence of the cp genome of Cistanche deserticola, a holoparasitic desert species belonging to the family Orobanchaceae