Toll-like receptor 4 on islet β cells senses expression changes in high-mobility group box 1 and contributes to the initiation of type 1 diabetes

Type 1 diabetes mellitus is caused by the autoimmune destruction of β cells within the islets. In recent years, innate immunity has been proposed to play a key role in this process. High-mobility group box 1 (HMGB1), an inflammatory trigger in a number of autoimmune diseases, activates proinflammatory responses following its release from necrotic cells. Our aim was to determine the significance of HMGB1 in the natural history of diabetes in non-obese diabetic (NOD) mice. We observed that the rate of HMGB1 expression in the cytoplasm of islets was much greater in diabetic mice compared with non-diabetic mice. The majority of cells positively stained for toll-like receptor 4 (TLR4) were β cells; few α cells were stained for TLR4. Thus, we examined the effects of anti-TLR4 antibodies on HMGB1 cell surface binding, which confirmed that HMGB1 interacts with TLR4 in isolated islets. Expression changes in HMGB1 and TLR4 were detected throughout the course of diabetes. Our findings indicate that TLR4 is the main receptor on β cells and that HMGB1 may signal via TLR4 to selectively damage β cells rather than α cells during the development of type 1 diabetes mellitus

Anti-kollision utrustning Tillämpad på lastbil

In modern society of industrialization, there are more and more trucks running on the roads transporting raw material or finished goods. With the rise of traffic accidents between cars and trucks, we need to put more attention to the tail of the truck. The authors design a device which can be fixed on the rear beams of the truck chassis. It’s called anti-collision equipment to avoid the cars crash into the truck tail. Although there are many available anti-collision solutions on trucks, studies show that there are still areas for improvement. The truck we choose to study is the heavy-duty truck of Jiefang J6M which is one of the mainstream models in China. The rear space of the truck is about 2400 mm (Width) × 2000 mm (Length) × 1050 mm (Height) and we design the device according to that size. Figure 1: Anti-collision Equipment Applied on Truck In other to achieve a better design, the authors study the literature and theses about energy absorption board, non-Newtonian fluid damper and thread shearing absorber. All of these three shock absorbers were combined together to make the design useful for different impact intensity. The height of the anti-collision is made adjustable for on-road and on-working site use. The authors design all the devices with Autodesk Inventor and validate material and dimensions by FEM Abaqus simulation. MATLAB simulation is used for calculating of fluid damper shock absorption. To make the best choice, the authors consider economic and reusability factors too.I det moderna samhället av industrialisering, det finns fler och fler lastbilar som kör på vägarna transporterar råmaterial eller färdiga varor. Med uppkomsten av trafikolyckor mellan bilar och lastbilar, måste vi lägga mer uppmärksamhet på svansen av lastbilen. Författarna utforma en anordning som kan fästas på de bakre balkar lastbilschassi. Det kallas anti-kollision utrustning för att undvika att bilar kraschar in i lastbilen svansen. Även om det finns många tillgängliga anti-kollision lösningar på lastbilar, studier visar att det fortfarande finns områden som kan förbättras. Lastbilen vi väljer att studera är den tunga lastbilen av Jiefang J6M som är en av de traditionella modeller i Kina. Den bakre utrymmet av lastbilen är omkring 2400 mm (bredd) x 2000 mm (längd) x 1050 mm (höjd) och vi utforma anordningen enligt den storleken.   Figur 1: Anti-kollision utrustning Tillämpad på lastbil I andra att uppnå en bättre konstruktion, författarna studera litteratur och avhandlingar om energiabsorberande ombord, icke-newtonska fluiddämpare och tråd klippning absorbator. Alla dessa tre stötdämpare kombinerades tillsammans för att göra utformningen användbart för olika konsekvenser intensitet. Höjden av anti-kollision görs justerbara för on-road och på arbetsplatsen användning. Författarna designar alla enheter med Autodesk Inventor och validera material och dimensioner av FEM Abaqus simulering. MATLAB simulering används för beräkning av fluiddämpare stötdämpning. För att göra det bästa valet, anser författarna ekonomiska och återanvändbarhet faktorer också

Ultra-narrowband and rainbow-free mid-infrared thermal emitters enabled by a flat band design in distorted photonic lattices

Abstract Most reported thermal emitters to date employing photonic nanostructures to achieve narrow bandwidth feature the rainbow effect due to the steep dispersion of the involved high-Q resonances. In this work, we propose to realize thermal emissions with high temporal coherence but free from rainbow effect, by harnessing a novel flat band design within a large range of wavevectors. This feature is achieved by introducing geometric perturbations into a square lattice of high-index disks to double the period along one direction. As a result of the first Brillouin zone halving, the guided modes will be folded to the Γ point and interact with originally existing guided-mode resonances to form a flat band of dispersion with overall high Q. Despite the use of evaporated amorphous materials, we experimentally demonstrate a thermal emission with the linewidth of 23 nm at 5.144 μm within a wide range of output angles (from −17.5° to 17.5°)

A deep-learning approach for segmentation of liver tumors in magnetic resonance imaging using UNet++

Abstract Objective Radiomic and deep learning studies based on magnetic resonance imaging (MRI) of liver tumor are gradually increasing. Manual segmentation of normal hepatic tissue and tumor exhibits limitations. Methods 105 patients diagnosed with hepatocellular carcinoma were retrospectively studied between Jan 2015 and Dec 2020. The patients were divided into three sets: training (n = 83), validation (n = 11), and internal testing (n = 11). Additionally, 9 cases were included from the Cancer Imaging Archive as the external test set. Using the arterial phase and T2WI sequences, expert radiologists manually delineated all images. Using deep learning, liver tumors and liver segments were automatically segmented. A preliminary liver segmentation was performed using the UNet + + network, and the segmented liver mask was re-input as the input end into the UNet + + network to segment liver tumors. The false positivity rate was reduced using a threshold value in the liver tumor segmentation. To evaluate the segmentation results, we calculated the Dice similarity coefficient (DSC), average false positivity rate (AFPR), and delineation time. Results The average DSC of the liver in the validation and internal testing sets was 0.91 and 0.92, respectively. In the validation set, manual and automatic delineation took 182.9 and 2.2 s, respectively. On an average, manual and automatic delineation took 169.8 and 1.7 s, respectively. The average DSC of liver tumors was 0.612 and 0.687 in the validation and internal testing sets, respectively. The average time for manual and automatic delineation and AFPR in the internal testing set were 47.4 s, 2.9 s, and 1.4, respectively, and those in the external test set were 29.5 s, 4.2 s, and 1.6, respectively. Conclusion UNet + + can automatically segment normal hepatic tissue and liver tumors based on MR images. It provides a methodological basis for the automated segmentation of liver tumors, improves the delineation efficiency, and meets the requirement of extraction set analysis of further radiomics and deep learning

Coupling mass balance analysis and multi-criteria ranking to assess the commercial-scale synthetic alternatives: a case study on glyphosate

Department of Science, Technology and Standards of China's Ministry of Environmental Protection [201009059]; China's Ministry of Science and Technology [2006BAC02A16]Quantitative and systematical assessment of the greenness of synthetic alternatives is one of the key topics of green chemistry. By coupling mass balance analysis and multi-criteria decision analysis, the paper seeks to assess the greenness of three commercial-scale production processes of a broad spectrum herbicide named glyphosate on the basis of seven assessment criteria and sixteen metrics. The seven criteria include mass intensity, efficiency of four core elements (i.e., carbon, nitrogen, phosphorous, and chlorine), energy consumption, nature of the industrial waste, cost of raw materials, and toxicity of materials. The multi-criteria decision method is applied to rank the greenness of glyphosate's three synthetic alternatives in a comprehensive, aggregate manner. Our findings highlight the discrepancy between greenness-driven alternative and cost-driven alternative in fine chemical production. At present, the actual choice of glyphosate production process in China remains dominated by the economic criteria rather than a more comprehensive, balanced set of criteria spanning economic profitability, environmental soundness, and social responsibility. Nonetheless, the underlining research method is relevant to the choice of synthetic alternatives of other fine chemicals

Significant CircRNAs in liver cancer stem cell exosomes: mediator of malignant propagation in liver cancer?

Abstract Hepatocellular carcinoma (HCC), one of the most prevalent forms of cancer worldwide, presents a significant global healthcare challenge. Cancer stem cells (CSCs), which can influence neighboring non-CSCs, are believed to play a crucial role in tumor growth and resistance to treatment, but the specific mechanisms and mediators are not fully understood. Regulation of the CSC state is considered an ideal therapeutic strategy both in the early stages of tumor formation and within established tumors. Exosomes have emerged as key players in intercellular communication, similar to classical hormone signaling, and are essential for facilitating communication between cells in liver cancer. Here, by coupling immunomagnetic bead sorting and exosomal sequencing, we found that exosome-derived circRNAs enriched in liver cancer CSCs were the key subsets with stemness characteristics and ultimately promoted HCC development. Of interest, we found that circ-ZEB1 and circ-AFAP1 are strongly correlated with liver cancer stemness and a poor prognosis, and can regulate the epithelial-mesenchymal transition (EMT) process. Our novel exosome-derived circRNAs play a vital role as key components of various intercellular crosstalk and communication systems in malignant transmission. This finding not only provides valuable support for utilizing plasma exosomal circRNAs as clinical prognostic indicators for HCC patients but also highlights a new research direction in exploring the signaling between liver CSCs and the messenger molecules contained within exosomes

HLF promotes ovarian cancer progression and chemoresistance via regulating Hippo signaling pathway

Abstract Hepatic leukemia factor (HLF) is aberrantly expressed in human malignancies. However, the role of HLF in the regulation of ovarian cancer (OC) remains unknown. Herein, we reported that HLF expression was upregulated in OC tissues and ovarian cancer stem cells (CSCs). Functional studies have revealed that HLF regulates OC cell stemness, proliferation, and metastasis. Mechanistically, HLF transcriptionally activated Yes-associated protein 1 (YAP1) expression and subsequently modulated the Hippo signaling pathway. Moreover, we found that miR-520e directly targeted HLF 3′-UTR in OC cells. miR-520e expression was negatively correlated with HLF and YAP1 expression in OC tissues. The combined immunohistochemical (IHC) panels exhibited a better prognostic value for OC patients than any of these components alone. Importantly, the HLF/YAP1 axis determines the response of OC cells to carboplatin treatment and HLF depletion or the YAP1 inhibitor verteporfin abrogated carboplatin resistance. Analysis of patient-derived xenografts (PDXs) further suggested that HLF might predict carboplatin benefits in OC patients. In conclusion, these findings suggest a crucial role of the miR-520e/HLF/YAP1 axis in OC progression and chemoresistance, suggesting potential therapeutic targets for OC

Reduced regional homogeneity in bilateral frontostriatal system relates to higher impulsivity behavior in codeine-containing cough syrups dependent individuals.

BACKGROUND: In the past twenty years, codeine-containing cough syrups (CCS) was recognized as a new type of addictive drugs. However, the exact neurobiologic mechanisms underlying CCS-dependence are still ill-defined. The aims of this study are to identify CCS-related modulations of neural activity during the resting-state in CCS-dependent individuals and to investigate whether these changes of neural activity can be related to duration of CCS use, the first age of CCS use and impulse control deficits in CCS-dependent individuals. We also want to observe the impact of gray matter deficits on these functional results. METHODOLOGY/PRINCIPAL FINDINGS: Thirty CCS-dependent individuals and 30 control subjects participated. Resting-state functional MRI was performed by using gradient-echo echo-planar imaging sequence. Regional homogeneity (ReHo) was calculated by using REST software. Voxel-based analysis of the ReHo maps between controls and CCS-dependent groups was performed using two-sample t tests (p<0.05, corrected for multiple comparisons). The Barratt Impulsiveness Scale 11 (BIS.11) was surveyed to assess participants' impulsivity trait soon after MR examination. Abnormal clusters revealed by group comparison were extracted and correlated with impulsivity, duration of CCS use, and age of first CCS use. ReHo was diminished in the bilateral medial orbitofrontal cortex (mOFC) and left dorsal striatum in CCS-dependent individuals. There were negative correlations between mean ReHo in the bilateral medial OFC, left dorsal striatum and duration of CCS use, BIS.11 total scores, and the subscale of attentional impulsivity in CCS-dependent individuals. There was a significantly positive correlation between mean ReHo in the left dorsal striatum and age of first CCS use in CCS-dependent individuals. Importantly, these results still remain significant after statistically controlling for the regional gray matter deficits. CONCLUSION: Resting-state abnormalities in CCS-dependent individuals revealed in the present study may further improve our understanding about the neural substrates of impulse control dysfunction in CCS-dependent individuals

Longitudinal brain structural alterations in patients with nasopharyngeal carcinoma early after radiotherapy

Background and purpose: To investigate effects of radiotherapy on normal brain tissue using in vivo neuroimaging in patients with nasopharyngeal carcinoma (NPC). Methods and materials: We used longitudinal MRI to monitor structural brain changes during standard radiotherapy in patients newly diagnosed with NPC. We assessed volumetric measures in 63 patients at 2–3 time points before and after radiotherapy, with 20 NPC-free participants as normal controls. Images were processed using validated software (FreeSurfer). Automated results were inspected visually for accuracy. We examined changes in volume of the whole brain, gray matter, white matter, and ventricles, as well as in cerebral volumes partitioned into temporal, frontal, parietal, and occipital lobes. A linear mixed model was used to evaluate longitudinal changes in these measurements. Statistical significance was evaluated at p < 0.05, which was corrected for multiple comparisons. Results: Volumes of the gray matter, and bilateral temporal lobes decreased in a time-dependent manner, whereas ventricle volume showed a time-dependent increase after radiotherapy. No volume changes were detected in NPC patients before radiotherapy when compared normal controls. No volume changes were detected in the subcohort of patients after completion of induction chemotherapy but prior to initiation of radiotherapy. Changes of bilateral temporal lobe volume correlated with irradiation dose in this region. Expansion of the ventricles correlated with a reduction in cognition assessment. Conclusions: We detected significant and progressive radiotherapy-associated structural changes in the brains of patients with NPC who were treated with standard radiotherapy, especially in the bilateral temporal lobe in which the effect was dose-dependent. Expansion of the ventricles can serve as an imaging marker for treatment-related reduction in cognitive function. Future studies with longer follow-ups are needed to evaluate morphometric changes long-term after radiotherapy. Keywords: Radiotherapy, Nasopharyngeal carcinoma (NPC), MRI, Structural, Brai