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Abstract Hypoxia can cause a variety of diseases, including ischemic stroke and neurodegenerative diseases. Within a certain range of partial pressure of oxygen, cells can respond to changes in oxygen. Changes in oxygen concentration beyond a threshold will cause damage or even necrosis of tissues and organs, especially for the central nervous system. Therefore, it is very important to find appropriate measures to alleviate damage. MiRNAs can participate in the regulation of hypoxic responses in various types of cells. MiRNAs are involved in regulating hypoxic responses in many types of tissues by activating the hypoxia-inducible factor (HIF) to affect angiogenesis, glycolysis and other biological processes. By analyzing differentially expressed miRNAs in hypoxia and hypoxia-related studies, as well as the HT22 neuronal cell line under hypoxic stress, we found that the expression of miR-18a was changed in these models. MiR-18a could regulate glucose metabolism in HT22 cells under hypoxic stress by directly regulating the 3’UTR of the Hif1a gene. As a small molecule, miRNAs are easy to be designed into small nucleic acid drugs, so this study can provide a theoretical basis for the research and treatment of nervous system diseases caused by hypoxia. Graphical Abstract

Abstract Fat loss predicts adverse outcomes in advanced heart failure (HF). Disrupted circadian clocks are a primary cause of lipid metabolic issues, but it's unclear if this disruption affects fat expenditure in HF. To address this issue, we investigated the effects of disruption of the BMAL1/REV-ERBα circadian rhythmic loop on adipose tissue metabolism in HF.50 Wistar rats were initially divided into control (n = 10) and model (n = 40) groups. The model rats were induced with HF via monocrotaline (MCT) injections, while the control group received equivalent solvent injections. After establishing the HF model, the model group was further subdivided into four groups: normal rhythm (LD), inverted rhythm (DL), lentivirus vector carrying Bmal1 short hairpin RNA (LV-Bmal1 shRNA), and empty lentivirus vector control (LV-Control shRNA) groups, each with 10 rats. The DL subgroup was exposed to a reversed light–dark cycle of 8 h: 16 h (dark: light), while the rest adhered to normal light–dark conditions (light: dark 12 h: 12 h). Histological analyses were conducted using H&E, Oil Red O, and Picrosirius red stains to examine adipose and liver tissues. Immunohistochemical staining, RT-qPCR, and Western blotting were performed to detect markers of lipolysis, lipogenesis, and beiging of white adipose tissue (WAT), while thermogenesis indicators were detected in brown adipose tissue (BAT). The LD group rats exhibited decreased levels of BMAL1 protein, increased levels of REV-ERBα protein, and disrupted circadian circuits in adipose tissue compared to controls. Additionally, HF rats showed reduced adipose mass and increased ectopic lipid deposition, along with smaller adipocytes containing lower lipid content and fibrotic adipose tissue. In the LD group WAT, expression of ATGL, HSL, PKA, and p-PKA proteins increased, alongside elevated mRNA levels of lipase genes (Hsl, Atgl, Peripilin) and FFA β-oxidation genes (Cpt1, acyl-CoA). Conversely, lipogenic gene expression (Scd1, Fas, Mgat, Dgat2) decreased, while beige adipocyte markers (Cd137, Tbx-1, Ucp-1, Zic-1) and UCP-1 protein expression increased. In BAT, HF rats exhibited elevated levels of PKA, p-PKA, and UCP-1 proteins, along with increased expression of thermogenic genes (Ucp-1, Pparγ, Pgc-1α) and lipid transportation genes (Cd36, Fatp-1, Cpt-1). Plasma NT-proBNP levels were higher in LD rats, accompanied by elevated NE and IL-6 levels in adipose tissue. Remarkably, morphologically, the adipocytes in the DL and LV-Bmal1 shRNA groups showed reduced size and lower lipid content, while lipid deposition in the liver was more pronounced in these groups compared to the LD group. At the gene/protein level, the BMAL1/REV-ERBα circadian loop exhibited severe disruption in LV-Bmal1 shRNA rats compared to LD rats. Additionally, there was increased expression of lipase genes, FFA β oxidation genes, and beige adipocyte markers in WAT, as well as higher expression of thermogenic genes and lipid transportation genes in BAT. Furthermore, plasma NT-proBNP levels and adipose tissue levels of NE and IL-6 were elevated in LV-Bmal1 shRNA rats compared with LD rats. The present study demonstrates that disruption of the BMAL1/REV-ERBα circadian rhythmic loop is associated with fat expenditure in HF. This result suggests that restoring circadian rhythms in adipose tissue may help counteract disorders of adipose metabolism and reduce fat loss in HF.

The concept of low-dose radiation (LDR)-induced hormetic responses was initially observed approximately 70 years ago and systematically reviewed along with the discovery of LDR-induced adaptive responses in a cytogenetic in vitro study in 1980s. By the end of the 1990s, discussions regarding the potential applications of LDR-induced hormesis and adaptive responses for preventing or treating chronic diseases, such as Alzheimer’s disease (AD) had taken place. Until 2016, reports on radiotherapy for the subjects with AD and for genetic AD model mice were published. Subsequently, several preclinical studies with animal models of AD and clinical studies in AD subjects were conducted. A significant milestone was achieved with the online availability of a new Systematic Review based on qualified publications from these preclinical and clinical studies. This mini-review provides a concise historical introduction to LDR-induced hormesis and adaptive responses with discussion of AD radiotherapy with either LDR or relatively high dose radiation. Highlights of this Systematic Review cover promising outcomes, challenges, and new questions, followed by discussion of potential mechanisms.

Abstract Objectives The endometrium of most unexplained infertility (UI) patients has been altered histologically. Shear wave elastography (SWE) is utilized to assess the signature of living tissue. This study aimed to explore the value of SWE in evaluating endometrial receptivity (ER) in UI patients. Methods In total, 59 UI patients (UI group) and 52 normal control women (NC group) who received fertility consultation in our hospital were included between January 2022 and June 2023. We divided them into the late-proliferative phase of UI group (LPUI; n = 59), mid-secretory phase of UI group (MPUI; n = 41), late-proliferative phase of NC group (LPNC; n = 52), and mid-secretory phase of NC group (MPNC; n = 45). Transvaginal ultrasonography and SWE were performed during the LP and MP. Endometrial thickness (EMT), uterine artery pulsatility index (UA-PI), endometrial mean elasticity (E-mean), and mean shear wave velocities (SWV-mean) were measured. Results There were significant differences in E-mean, SWV-mean, EMT, and UA-PI between the UI group and the NC group during both the LP and MP (p MPNC vs MPUI < 0.05, p LPNC vs LPUI < 0.05). E-mean and SWV-mean decreased with increasing EMT but increased with increasing UA-PI (p < 0.05). The most effective parameter for evaluating ER in UI patients is the E-mean (AUC = 0.89). Conclusions UI patients exhibited thinner endometrium, increased endometrial stiffness, and poor endometrial blood perfusion. E-mean was the most effective parameter to evaluate ER in UI patients. The study preliminarily proved that SWE is a promising non-invasive tool for evaluating the condition of endometrium. Critical relevance statement This study aimed to explore the significance of endometrial elasticity measured by SWE in evaluating patients with UI. The findings revealed a correlation between EMT, UA-PI, and E-mean. Endometrial elasticity can serve as an effective indicator for predicting ER. Key points 1. To explore the significance of endometrial elasticity in assessing patients with UI. 2. The endometrium of UI patient exhibited thinness, stiffness, and poor blood perfusion. 3. Endometrial elasticity serves as a valuable indicator for evaluating endometrial receptivity. Graphical Abstract

Abstract U-10 wt.% Zr (U-10Zr) metallic fuel is the leading candidate for next-generation sodium-cooled fast reactors. Porosity is one of the most important factors that impacts the performance of U-10Zr metallic fuel. The pores generated by the fission gas accumulation can lead to changes in thermal conductivity, fuel swelling, Fuel-Cladding Chemical Interaction (FCCI) and Fuel-Cladding Mechanical Interaction (FCMI). Therefore, it is crucial to accurately segment and analyze porosity to understand the U-10Zr fuel system to design future fast reactors. To address the above issues, we introduce a workflow to process and analyze multi-source Scanning Electron Microscope (SEM) image data. Moreover, an encoder-decoder-based, deep fully convolutional network is proposed to segment pores accurately by integrating the residual unit and the densely-connected units. Two SEM 250 × field of view image datasets with different formats are utilized to evaluate the new proposed model’s performance. Sufficient comparison results demonstrate that our method quantitatively outperforms two popular deep fully convolutional networks. Furthermore, we conducted experiments on the third SEM 2500 × field of view image dataset, and the transfer learning results show the potential capability to transfer the knowledge from low-magnification images to high-magnification images. Finally, we use a pre-trained network to predict the pores of SEM images in the whole cross-sectional image and obtain quantitative porosity analysis. Our findings will guide the SEM microscopy data collection efficiently, provide a mechanistic understanding of the U-10Zr fuel system and bridge the gap between advanced characterization to fuel system design.

Abstract Gaseous fission products from nuclear fission reactions tend to form fission gas bubbles of various shapes and sizes inside nuclear fuel. The behavior of fission gas bubbles dictates nuclear fuel performances, such as fission gas release, grain growth, swelling, and fuel cladding mechanical interaction. Although mechanical understanding of the overall evolution behavior of fission gas bubbles is well known, lacking the quantitative data and high-level correlation between burnup/temperature and microstructure evolution blocks the development of predictive models and reduces the possibility of accelerating the qualification for new fuel forms. Historical characterization of fission gas bubbles in irradiated nuclear fuel relied on a simple threshold method working on low-resolution optical microscopy images. Advanced characterization of fission gas bubbles using scanning electron microscopic images reveals unprecedented details and extensive morphological data, which strains the effectiveness of conventional methods. This paper proposes a hybrid framework, based on digital image processing and deep learning models, to efficiently detect and classify fission gas bubbles from scanning electron microscopic images. The developed bubble annotation tool used a multitask deep learning network that integrates U-Net and ResNet to accomplish instance-level bubble segmentation. With limited annotated data, the model achieves a recall ratio of more than 90%, a leap forward compared to the threshold method. The model has the capability to identify fission gas bubbles with and without lanthanides to better understand the movement of lanthanide fission products and fuel cladding chemical interaction. Lastly, the deep learning model is versatile and applicable to the micro-structure segmentation of similar materials.

The functionality and excellent low temperature dyeability of wool fabrics play a crucial role in expanding their potential applications in the fields of healthcare and technical textiles. The study proposes a highly effective modification method to impart coloration enhancement and functionality for wool fibers using lipoic acid (LA) as a coupling agent to bind hydroxypropyl-β-cyclodextrin (HP-β-CD) capped magnetic nanoparticles (Fe3O4). The structure and morphology of the modified wool fabrics (MWF) were characterized by various measure techniques including FT-ATR, FE-SEM/EDS, XRD, X-ray photoelectron spectroscopy (XPS) and thermogravimetric analysis (TG). The results demonstrated the successful immobilization of HP-β-CD capped Fe3O4 nanoparticles on the surface of wool fibers through LA. The MWF exhibited enhanced wettability, anti-wrinkle performance, improved UV resistance, effective antioxidation, and good antibacterial effect against Gram-positive (Staphylococcus aureus). These properties were found to be dosage-dependent on LA. In addition, the dyed MWF with Curcumin and Acid red 1 demonstrated higher color strength compared to untreated wool, and the color strength (K/S value) reached to 17.1 and 23.4 respectively when using 4% (o.w.f) dye concentration at 80℃ without any pH adjustment. Furthermore, the dyed MWF with both dyes exhibited the improved rubbing and washing colorfastness. This study presents a potential effective approach for enhancement in the bio-functionality and dyeability of wool fabrics.

This is an editorial from the new editor-in-chief, EIC, who starts his role in March 2024. Due to the remarkable advance of various research fields in terms of its concepts and technology, the emerging concepts of “Exposome” and associated “Exposomics” have been introduced into the toxicology research. Therefore, the mission of “Dose-Response” will remain adhered to the original goals but will incorporate with these new concepts as the next chapter’s principle and strategies. Accordingly, although it remains with special interest in the biological response to low-dose (level) ranges of stresses. The types and contents of interested manuscripts will be extended with more diverse, newer concepts from a wide range of disciplines. We wish this journal can open a door for various discipline scientists and researchers to share their state-of-the-art discoveries to shed new insight to understand the impact of environmental and toxicological medicine and develop more specific and effective intervention strategies.

ABSTRACTThe quality of fish pre-treatment processing directly affected the production competitiveness of the fish industry. The removal of heads and tails is one of the key technologies in the fish processing. This study proposed an identification method of fish head and tail, and the original YOLOV3 model was improved by replacing the backbone feature extraction network of the YOLOV3 model with the lightweight neural network MobileNetv3. Firstly, a freshwater fish image dataset was created and divided into the training, validation and test sets with the assigned ratio of 6:2:2. Next, the freshwater fish dataset was trained using the target detector YOLOV3. Finally, the average accuracy mAP (mean of Average Precision) and the average image detection time were used as the accuracy and speed indexes to evaluate the detection effect of the model. In addition, the SSD-MobileNetv3 and SSD-VGG16 were introduced into present study and they were compared with the improved algorithm. The experimental results showed that the detection speed of the YOLOV3 model with MobileNetV3 was significantly improved. The mAP of YOLOV3-MobileNetv3 model was 98.36%, the inference speed was 28.2 ms, which was 5.09%, 4.24% and 2.07% higher than the mAP of other three models (SSD-VGG16, SSD-MobileNetv3 and YOLOV3-Darknet-53), and the average detection time shortened by 86%, 9.99% and 29%, respectively. Therefore, this experimental method of head and tail of freshwater fish could achieve real-time detection and recognition of various kinds of freshwater fish, which had the great advantages of high detection accuracy and fast detection speed.

We are facing a critical aging crisis, with geriatric populations (65+) growing to unprecedented proportions and ~4 million people (a 6.5-fold increase) expected to become centenarians by 2050. This is compounded by environmental pollution, which affects individuals of all ages and contributes to age-related diseases. As we have a limited understanding of how environmental pollutants affect older populations distinctly from younger populations, these longer-lived geriatric populations present a key knowledge gap. To address this knowledge gap, we employ a “Toxic Aging Coin” approach: heads consider how age impacts chemical toxicity, and tails consider how chemicals act as gerontogens—or how they accelerate biological aging. We employed this approach to investigate hexavalent chromium (Cr[VI]) impacts on female rats exposed to 0.05 or 0.1 mg Cr(VI)/L in drinking water for 90 days; these are the maximum contaminant levels (i.e., the highest levels permitted) from the World Health Organization and U.S. Environmental Protection Agency, respectively. During exposure, rats performed a battery of behavior assays to assess grip strength, locomotor coordination, anxiety, spatial memory, sociability, and social novelty preference. We observed age differences in Cr(VI) neurotoxicity, with grip strength, locomotor function, and spatial memory in middle-aged females being particularly affected. We further compared these results in females to results in males, noting many sex differences, especially in middle-aged rats. These data emphasize the need to consider age and sex as variables in toxicology and to revisit drinking water regulations for Cr(VI).

Microplastic pollution in agricultural soil threatens soil quality and human health which has attracted extensive attention worldwide. However, there is no uniform standard for microplastic extraction methods and the identification of microplastic component in different typical agricultural soils. In this study, an artificial simulation adding experiment was used in eight typical agricultural soil samples in China. The aim of the study was to use different methods for extraction, comparing the extraction rates of four microplastics and their influence on polymer identification using ATR- FTIR. The two separate methods were oil extraction (water + oil and saturated NaCl solution + oil), and density method (saturated NaCl solution). The four types of microplastics include polyethylene terephthalate (PET), polypropylene (PP), polystyrene (PS), and polyethylene (PE). We found that the oil extraction method effectively extracted four types of microplastics in agricultural soils, which varied from 83.33% to 100.00%. However, the extraction rate of PET under the oil extraction method and PP under the density method from Southern laterite area was lower than other soils. The presence of iron and aluminum ions influenced the extraction rates of microplastics in the Southwest laterite area. With the increase in microplastic density, the extraction rates of the density method decrease. The oil extraction methods with the cleaning of residual oil were recommended for the higher density microplastics. The density method was recommended for the lighter microplastics in agricultural soils. However, these two extraction methods were not ideal to extract the microplastics from the Southern laterite area and the appropriate extraction methods for laterite need to be further studied in the future. Our results can provide technical support for the extraction treatment and scientific microplastic pollution control of typical agricultural soils with different erosion areas.

In recent years, severe traffic congestion in urban areas has become a growing concern for many cities in China. While beltway expressways have been built to alleviate urban congestion by diverting traffic away from city centers, existing preferential access schemes have led to overuse of certain beltway links and a decline in service levels. This research is motivated by the need to develop an improved scheme that balances urban traffic relief and beltway service level maintenance. To benefit both the government and the beltway expressway company, we propose a tradable credit scheme (TCS) to shift some of the traffic burden from urban roads to the beltway expressway while maintaining its current service level. In order to determine an appropriate TCS, a biobjective bilevel programming model is introduced. The upper-level model seeks to maximize the revenue of the beltway expressway company while minimizing the system travel time as specified by the traffic management department. The lower-level model describes user travel behavior under given TCS and capacity constraints of beltway expressway links, represented as the generalized capacitated traffic assignment problem. Additionally, an NSGA-II framework is designed to discover Pareto-optimal TCSs. Within this framework, a gradient projection method is utilized within the augmented Lagrangian multiplier algorithm to solve the lower-level problem and evaluate the fitness of the TCS. Numerical experiments demonstrate that implementing well-designed tradable credit schemes can effectively alleviate urban traffic congestion, reducing system travel time by up to 1.6%, while simultaneously increasing the beltway company’s revenue by up to 300% compared to the base case without requiring government subsidies. The sensitivity analysis results indicate the insufficiency of the existing preferential access or toll-free schemes on the beltway, highlighting the greater effectiveness of the integrated strategy proposed in this study.

AbstractObjective This study aimed to compare the repeatability and diagnostic efficiency of shear wave elastography (SWE) while using coupling gel and gel pads in the diagnosis of superficial breast lesions.Methods Two experienced sonographers, trained in SWE, used different methods to perform the maximum Young’s modulus (Emax) measurement of the lesion while using coupling gel SWE and gel pad SWE at different time points. All 80 lesions were in the superficial layer of the breast. The interclass correlation coefficient (ICC) was calculated to evaluate the intraobserver and interobserver repeatability. Meanwhile, the receiver operating characteristic curve (ROC curve) was used to calculate the sensitivity, specificity and area under the curve of the two methods.Results In the 80 breast lesions, the intraobserver and interobserver reproducibility of SWE measurements using coupling gel were considered good, and the ICCs were 0.728 (95% CI: 0.509–0.813) and 0.702 (95% CI: 0.492–0.795), respectively. The intraobserver and interobserver reproducibility of the SWE measured by the gel pad were also considered good, and the ICCs were 0.745 (95% CI: 0.501–0.801) and 0.713 (95% CI: 0.498–0.802), respectively. The sensitivity, specificity and area under the curve were 0.711 and 0.737, 0.929 and 0.905, and 0.873 and 0.878, respectively.Conclusions In the SWE measurement of superficial breast lesions, the use of a gel pad does not affect the repeatability and diagnostic efficiency of the measurement.

As a complex multiphase food, ice cream is composed of fat globules, bubbles and ice crystals dispersed in a semi-frozen solution. The fat content is usually 8%~16%, which plays an important role in the ice cream system. However, excessive fat intake can have a negative impact on health, so the use of fat substitutes to replace part or all of ice cream fat has become a research focus. This paper reviewed the research progress of fat substitutes in ice cream by domestic and foreign scholars in recent years, and focused on the introduction of different types of fat substitutes, as well as the effects on the physicochemical and sensory characteristics of low-fat ice cream. The applications were summarized and the future research direction and focus were also prospected.

Abstract U-10Zr Metal fuel is a promising nuclear fuel candidate for next-generation sodium-cooled fast spectrum reactors. Since the Experimental Breeder Reactor-II in the late 1960s, researchers accumulated a considerable amount of experience and knowledge on fuel performance at the engineering scale. However, a mechanistic understanding of fuel microstructure evolution and property degradation during in-reactor irradiation is still missing due to a lack of appropriate tools for rapid fuel microstructure assessment and property prediction based on post irradiation examination. This paper proposed a machine learning enabled workflow, coupled with domain knowledge and large dataset collected from advanced post-irradiation examination microscopies, to provide rapid and quantified assessments of the microstructure in two reactor irradiated prototypical annular metal fuels. Specifically, this paper revealed the distribution of Zr-bearing secondary phases and constitutional redistribution across different radial locations. Additionally, the ratios of seven different microstructures at various locations along the temperature gradient were quantified. Moreover, the distributions of fission gas pores on two types of U-10Zr annular fuels were quantitatively compared.

In our previous studies, we showed that the generation of ovarian tumors in NSG mice (immune-compromised) resulted in the induction of muscle and cardiac cachexia, and treatment with withaferin A (WFA; a steroidal lactone) attenuated both muscle and cardiac cachexia. However, our studies could not address if these restorations by WFA were mediated by its anti-tumorigenic properties that might, in turn, reduce the tumor burden or WFA’s direct, inherent anti-cachectic properties. To address this important issue, in our present study, we used a cachectic model induced by the continuous infusion of Ang II by implanting osmotic pumps in immunocompetent C57BL/6 mice. The continuous infusion of Ang II resulted in the loss of the normal functions of the left ventricle (LV) (both systolic and diastolic), including a significant reduction in fractional shortening, an increase in heart weight and LV wall thickness, and the development of cardiac hypertrophy. The infusion of Ang II also resulted in the development of cardiac fibrosis, and significant increases in the expression levels of genes (ANP, BNP, and MHCβ) associated with cardiac hypertrophy and the chemical staining of the collagen abundance as an indication of fibrosis. In addition, Ang II caused a significant increase in expression levels of inflammatory cytokines (IL-6, IL-17, MIP-2, and IFNγ), NLRP3 inflammasomes, AT1 receptor, and a decrease in AT2 receptor. Treatment with WFA rescued the LV functions and heart hypertrophy and fibrosis. Our results demonstrated, for the first time, that, while WFA has anti-tumorigenic properties, it also ameliorates the cardiac dysfunction induced by Ang II, suggesting that it could be an anticachectic agent that induces direct effects on cardiac muscles.

The water produced during the oxidative esterification reaction occupies the active sites and reduces the activity of the catalyst. In order to reduce the influence of water on the reaction system, a hydrophobic catalyst was prepared for the one-step oxidative esterification of methylacrolein (MAL) and methanol. The catalyst was synthesized by loading the active component Au onto ZnO using the deposition–precipitation method, followed by constructing the silicon shell on Au/ZnO using tetraethoxysilane (TEOS) to introduce hydrophobic groups. Trimethylchlorosilane (TMCS) was used as a hydrophobic modification reagent to prepare hydrophobic catalysts, which exhibited a water droplet contact angle of 111.2°. At a temperature of 80 °C, the hydrophobic catalyst achieved a high MMA selectivity of over 95%. The samples were characterized using XRD, N2 adsorption, ICP, SEM, TEM, UV-vis, FT-IR, XPS, and water droplet contact angle measurements. Kinetic analysis revealed an activation energy of 22.44 kJ/mol for the hydrophobic catalyst.

Rapidly and accurately extracting tobacco plant information can facilitate tobacco planting management, precise fertilization, and yield prediction. In the karst mountainous of southern China, tobacco plant identification is affected by large ground undulations, fragmented planting areas, complex and diverse habitats, and uneven plant growth. This study took a tobacco planting area in Guizhou Province as the research object and used DJI UAVs to collect UAV visible light images. Considering plot fragmentation, plant size, presence of weeds, and shadow masking, this area was classified into eight habitats. The U-Net model was trained using different habitat datasets. The results show that (1) the overall precision, recall, F1-score, and Intersection over Union (IOU) of tobacco plant information extraction were 0.68, 0.85, 0.75, and 0.60, respectively. (2) The precision was the highest for the subsurface-fragmented and weed-free habitat and the lowest for the smooth-tectonics and weed-infested habitat. (3) The weed-infested habitat with smaller tobacco plants can blur images, reducing the plant-identification accuracy. This study verified the feasibility of the U-Net model for tobacco single-plant identification in complex habitats. Decomposing complex habitats to establish the sample set method is a new attempt to improve crop identification in complex habitats in karst mountainous areas.

Alopecia areata (AA) is a non-scarring hair loss disorder. Alopecia totalis (AT) and alopecia universalis (AU) are the severe subtypes of AA. Age of onset before 6 years of age, disease duration of more than 1 year, and extensive alopecia involving more than 50% of the scalp (including AT or AU) suggest a poorer prognosis. Topical corticosteroids are the preferred first-line treatment for pediatric AA. While some treatments, such as intralesional corticosteroids, systemic steroids, contact immunotherapy with squaric acid dibutyl ester, and JAK inhibitors, showed efficacy in adults with AA, their safety profiles limit their use in pediatric AA patients. Dupilumab is a biologic that effectively addresses the patho-physiology of Th2 allergic diseases, and treats atopic diseases by inhibiting the helper Th2 immune axis. AA has been reported to be significantly improved with dupilumab for atopic dermatitis (AD) in children and adults. We report hair regrowth over all of the scalp, eyebrows, and eyelashes after 10 months of dupilumab therapy in a 4-year-old AU patient resistant to baricitinib.

The geological model plays an important role in geophysics and engineering geology. The data source of geological modeling comes from interpretation data, borehole data, and outcrop data. Due to economic and technical limitations, it is impossible to obtain highly accurate and high-density data sources. The sparsity and inaccuracy of data sources lead to the uncertainty in geological models. Unlike the problem of probability, there is not enough samples for a geological model. Spatial diffusion model and merging model are introduced, which are more satisfied with the cognition of uncertainty than the existing methods. And then, using conditional information entropy, a quantification method of geological uncertainty, is proposed. Compared with the approaches of information entropy, this method took full account of the constraints of geological laws. Based on the uncertainty models and conditional information entropy, a framework of uncertainty assessment in geological models is established. It is not necessary in our framework to create multiple geological models, which is a time-consuming and laborious task. The application of Hashan survey located at north of China shows that the method and framework of this study are reasonable and effective.

Abstract Background Astragalus polysaccharide (APS) is a key active ingredient isolated from Astragalus membranaceus that has been reported to be a potential treatment for obesity and diabetes by regulating lipid metabolism and adipogenesis, alleviating inflammation, and improving insulin resistance. However, whether APS regulates lipid metabolism in the context of cachexia remains unclear. Therefore, this study analysed the effects of APS on lipid metabolism and adipose expenditure in a heart failure (HF)-induced cardiac cachexia rat model. Methods A salt-sensitive hypertension-induced cardiac cachexia rat model was used in the present study. Cardiac function was detected by echocardiography. The histological features and fat droplets in fat tissue and liver were observed by H&E staining and Oil O Red staining. Immunohistochemical staining, Western blotting and RT‒qPCR were used to detect markers of lipolysis and adipose browning in white adipose tissue (WAT) and thermogenesis in brown adipose tissue (BAT). Additionally, sympathetic nerve activity and inflammation in adipose tissue were detected. Results Rats with HF exhibited decreased cardiac function and reduced adipose accumulation as well as adipocyte atrophy. In contrast, administration of APS not only improved cardiac function and increased adipose weight but also prevented adipose atrophy and FFA efflux in HF-induced cachexia. Moreover, APS inhibited HF-induced lipolysis and browning of white adipocytes since the expression levels of lipid droplet enzymes, including HSL and perilipin, and beige adipocyte markers, including UCP-1, Cd137 and Zic-1, were suppressed after administration of APS. In BAT, treatment with APS inhibited PKA-p38 MAPK signalling, and these effects were accompanied by decreased thermogenesis reflected by decreased expression of UCP-1, PPAR-γ and PGC-1α and reduced FFA β-oxidation in mitochondria reflected by decreased Cd36, Fatp-1 and Cpt1. Moreover, sympathetic nerve activity and interleukin-6 levels were abnormally elevated in HF rats, and astragalus polysaccharide could inhibit their activity. Conclusion APS prevented lipolysis and adipose browning in WAT and decreased BAT thermogenesis. These effects may be related to suppressed sympathetic activity and inflammation. This study provides a potential approach to treat HF-induced cardiac cachexia.

Promoting the uptake of dyes is an important part of the sustainable processing of wool products. This study presents an effective modification approach to enhance the dyeability of wool fabric with adenosine triphosphate as an activator, 3-carboxyphenyl boronic acid as a ligand-binding agent, and chitin whisker as a couple agent. The structure and surface morphology of the as-prepared wool fabric was characterized in detail. Natural luteolin and acid red 1 were used to dye the modified wool fabric, and the effect of different dyeing parameters on dyeing properties was discussed. The results indicated that the modified wool gained better surface color depth (K/S) and uptake without additional agents than the untreated wool fabric. When the modified wool fabric was dyed at 45 °C with luteolin and at 60 °C with acid red 1, the dyeing processes of the two dyes on the modified wool fabrics followed the Langmuir isotherm and the pseudo-second-order kinetic model. Furthermore, the dyed modified wool fabrics possessed improved color fastness. Overall, this work offers a facile, effective, and sustainable way to improve the low-temperature dyeability of wool products.

In this paper, we combine electrospinning with laminar flow theory to verify the influence of the spinning needle length on the internal structure of PVDF (polyvinylidene fluoride) nanofibers. The long spinning needle is referred as a reference like long ducts in the body of spiders. We also discussed the effect of different needle length on the micro-morphology, mechanical properties, electrical properties, porosity, and hydrophobic properties of PVDF nanofiber membranes. The results showed that when the needle length increased, more PVDF macromolecular chains will have sufficient time to be straightened and aligned, resulting in an increasingly ordered internal structure of the prepared PVDF nanofibers. The different length of the long needle has a certain influence on the morphology, mechanical properties, electrical properties, porosity, and hydrophobic properties of PVDF nanofiber membrane obtained by electrospinning. The more ordered the internal structure of nanofibers, the worse the membrane’s mechanical properties, but the lower its electrical resistivity.

The primary objective of this investigation was to study the effect of altitude on fish swimming ability. Different species were tested to ensure that the differences observed are not associated with a single species. Fish critical swimming speed and burst speed were determined using stepped-velocity tests in a Brett-type swimming respirometer. Based on the effects of water temperature and dissolved oxygen, it is clear that the swimming ability of fish decreases as altitude increases. Further, because the effects of high altitude on fish physiology go beyond the effects of lower temperature and dissolved oxygen, we recommend that fish swimming ability be tested at an altitude similar to the target fishway site to ensure the validity of fish data used for fishway design.

In order to explore the nutritional value and food safety in flower of different varieties of Hibiscus mutabilis L., the composition and contents in flower of 17 H. mutabilis cultivars were determined by inductively coupled plasma spectroscopy (ICP-OES), and were evaluated by principal component analysis, the pollution levels and potential health risks were estimated by provisional tolerated weekly intake (PTWI) and target hazard quotient (THQ), respectively. The results showed that the major elements K, Ca, Mg, and Na content ranged from 13564.921 to 24951.771, 1301.943 to 4786.171, 1724.442 to 3748.11 mg·kg−1 and 122.894 to 706.763 mg·kg−1 in flower of 17 H. mutabilis cultivars, respectively. The content range of 11 kinds of beneficial mineral elements: I, Zn, Fe, B, Al, Cu, Co, Mo, Mn, Si, V were 0.009~1.360, 17.880~81.381, 55.185~115.034, 19.281~52.571, 31.555~92.710, 6.220~13.308, 0.040~0.147, 0.320~3.286, 4.223~23.472, 0.062~0.193, 0.128~0.502 mg·kg−1, the contents of Cd, As, Pb and Cr in all the samples were not exceeded national standards. This indicated that the H. mutabilis flower was rich in mineral elements, safe for human consumption, and conducived to improving our dietary nutrition. The results of principal component analysis showed that 'JBY' had the highest comprehensive score and could be used as a suitable variety for the development of functional products. The highest average ratio of AWI to PTWI of the four harmful elements was no more than 10%, and the THQ was less than 1, the results indicated that trace elements intake form the flower of H. mutabilis had no significant health risk to people who consume it. The trace elements of As and Pb were the main risk elements, which had high contribution rate to HI.

BackgroundAlthough transforming growth factor-β (TGF-β)/Smad signaling pathway is important in regulating the occurrence and development of pulmonary fibrosis, the pathogenesis of pulmonary fibrosis remains elusive. ObjectiveTo explore the functions of genes associated with TGF-β/Smad signaling pathway in the progression of pulmonary fibrosis. MethodsA NIH-3T3 fibroblast model induced by TGF-β1 was established. The experiment samples were divided into a control group and a TGF-β1 treatment group. The control group was exposed to normal saline, while the TGF-β1 treatment group was exposed to 10 ng·mL−1 TGF-β1 for 12 h. The RNAs of the two groups were extracted, sequenced, and analyzed by bioinformatics methods to identify seven key genes in TGF-β pathway, including Dcn, Smad3, Smad7, Fbn1, Thbs1, TGF-β1, and TGF-β3. The gene expression levels of five markers [Collagen1α1, Collagen1α2, α-smooth muscle actin (α-SMA), TGF-β1, and TGF-β3] and the seven key genes were detected by quantitative real-time PCR (qRT-PCR). The proteins of the two groups were extracted. The important marker protein expression levels of Smad3, the phosphorylation of Smad3 (P-Smad3), and α-SMA were detected by Western blotting. At the same time, 30 healthy SPF-grade C57BL/6 mice were randomly divided into three groups, with 10 mice in each group: a control group, a SiO2 inhalation exposure group for 28 d (10 mice), and a SiO2 inhalation exposure group for 56 d (10 mice). The mice in the two treatment groups were exposed to a natural SiO2 environment for 4 h per day with a 10-min pause for breathing fresh air at 2 h intervals. The lung tissues of the mice were taken after execution. The changes of pulmonary fibrosis were detected by Masson staining, and mRNAs and proteins were extracted to detect the expression of the above key genes and proteins. ResultsThe expression levels of the five marker genes Collagen1α1, Collagen1α2, α-SMA, TGF-β1, and TGF-β3 were significantly increased in the TGF-β1-induced NIH-3T3 fibroblasts than those in the control group (P < 0.01); the expression levels of P-Smad3 and α-SMA proteins increased significantly (P < 0.01); the expression results of the seven key genes screened in the TGF pathway were that Dcn and Smad3 were obviously down-regulated (P < 0.01), and Smad7, Fbn1, Thbs1, TGF-β1, and TGF-β3 were obviously up-regulated (P < 0.01). The changes in gene expression levels of the transcriptome sequencing showed the same trend. The results of Masson staining showed that the content of collagen fibers in the lung tissues also increased in the SiO2 inhalation exposure groups over time. In the mouse experiment, five marker genes were obviously up-regulated compared with the control group (P < 0.01); no obvious change was found in the expression of Smad3 protein, and the expression levels of P-Smad3 and α-SMA were obviously higher in the SiO2 exposure groups than those in the control group (P < 0.01); the expression levels of Dcn and Smad3 showed a down-regulated trend, while the expression levels of Smad7, Fbn1, Thbs1, TGF-β1, and TGF-β3 showed an up-regulated trend with the increase of SiO2 inhalation exposure days (P < 0.01). The expression levels of the above five marker genes, three important marker proteins, and seven key genes were consistent with the expression trends of TGF-β1-induced NIH-3T3 fibroblasts. ConclusionThe expression levels of pulmonary fibrosis-related marker genes and proteins change significantly in TGF-β1-induced fibroblast cells, and the lung tissues of mice under natural SiO2 inhalation exposure has obvious fibrosis characteristics. Seven genes (Dcn, Smad3, Smad7, Fbn1, Thbs1, TGF-β1, and TGF-β3) may be involved in the regulation of pulmonary fibrosis by the TGF-β/Smad signaling pathway.

BackgroundThe main pathological feature of silicosis is pulmonary fibrosis. Multiple miRNAs regulate the development of silicosis.ObjectiveUsing a fibroblast cell line, to explore the effect of miR-18a on the expression of extracellular matrix-related genes, and verify the mechanism.MethodsThe fibroblast cell line NIH-3T3 cells were transfected with miR-18a mimics or neurogenic locus notch homolog protein 2 (Notch2) small interfering RNA (siRNA). The mRNA expression changes of Acta2, Col1a1, and Notch2 were detected by real-time quantitative reverse transcription PCR (qRT-PCR), α-smooth muscle actin (α-SMA) and Notch2 were also detected at the protein level by Western blotting. To verify whether miR-18a could directly act on the complementary sequences of the Notch2 gene, human embryonic kidney HEK293T cells and the psiCHECKTM-2 vector were used.ResultsThe results of qRT-PCR showed that in NIH-3T3 cells, the over-expression of miR-18a mimics for 36 h inhibited the mRNA expression of Col1a1 and Acta2 (P

The kidney plays a central role in maintaining the fluid and electrolyte homeostasis in the body. Bicarbonate transporters NBCn1, NBCn2, and AE2 are expressed at the basolateral membrane of the medullary thick ascending limb (mTAL). In a previous study, NBCn1, NBCn2, and AE2 are proposed to play as a regulatory pathway to decrease NaCl reabsorption in the mTAL under high salt condition. When heterologously expressed, the activity of these transporters could be stimulated by the InsP3R binding protein released with inositol 1,4,5-trisphosphate (IRBIT), L-IRBIT (collectively the IRBITs), or protein phosphatase PP1. In the present study, we characterized by immunofluorescence the expression and localization of the IRBITs, and PP1 in rat kidney. Our data showed that the IRBITs were predominantly expressed from the mTAL through the distal renal tubules. PP1 was predominantly expressed in the TAL, but is also present in high abundance from the distal convoluted tubule through the medullary collecting duct. Western blotting analyses showed that the abundances of NBCn1, NBCn2, and AE2 as well as the IRBITs and PP1 were greatly upregulated in rat kidney by dietary sodium. Co-immunoprecipitation study provided the evidence for protein interaction between NBCn1 and L-IRBIT in rat kidney. Taken together, our data suggest that the IRBITs and PP1 play an important role in sodium handling in the kidney. We propose that the IRBITs and PP1 stimulates NBCn1, NBCn2, and AE2 in the basolateral mTAL to inhibit sodium reabsorption under high sodium condition. Our study provides important insights into understanding the molecular mechanism for the regulation of sodium homeostasis in the body.

Nucleosomes not only serve as the basic building blocks for eukaryotic chromatin but also regulate many biological processes, such as DNA replication, repair, and recombination. To modulate gene expression in vivo, the histone variant H2A.Z can be dynamically incorporated into the nucleosome. However, the assembly dynamics of H2A.Z-containing nucleosomes remain elusive. Here, we demonstrate that our previous chemical kinetic model for nucleosome assembly can be extended to H2A.Z-containing nucleosome assembly processes. The efficiency of H2A.Z-containing nucleosome assembly, like that of canonical nucleosome assembly, was also positively correlated with the total histone octamer concentration, reaction rate constant, and reaction time. We expanded the kinetic model to represent the competitive dynamics of H2A and H2A.Z in nucleosome assembly, thus providing a novel method through which to assess the competitive ability of histones to assemble nucleosomes. Based on this model, we confirmed that histone H2A has a higher competitive ability to assemble nucleosomes in vitro than histone H2A.Z. Our competitive kinetic model and experimental results also confirmed that in vitro H2A.Z-containing nucleosome assembly is governed by chemical kinetic principles.

A series of Yttrium (Y)-doped Bi2MoO6 composites with calcined mussel shell powder (CMS) as supports were synthesized using a solvothermal method. The as-prepared samples were analyzed using multiple techniques to investigate their microscopic morphology, composition structure, and optical properties. The photocatalytic performance of the as-prepared samples was assessed via examining their capacity to degrade Rhodamine B (RhB) under visible-light irradiation. The photocatalytic data showed that the Y-doped Bi2MoO6/CMS composites exhibited better photocatalytic activity compared to pure Bi2MoO6 and undoped Bi2MoO6/CMS samples. Among the samples, the 0.5%Y-doped Bi2MoO6/CMS (0.5%Y-BC) showed the highest photocatalytic activity, achieving a maximum degradation rate of 99.7% within 60 min. This could be attributed to highly reactive sites due to Y doping, a narrower band gap, and a lower recombination rate of photoinduced electron–hole pairs. Additionally, the 0.5%Y-BC photocatalyst exhibited excellent stability and reusability properties even after four cycles, making it suitable for practical applications. The findings provided a feasible synthesis of nanocomposite photocatalysts with outstanding properties for organic pollutant removal from the solution system.

Abstract. Background:. Previous studies suggested higher serum N-terminal-pro-B-type natriuretic peptide (NT-proBNP) level with older age and in women, but the reference intervals (RIs) recommended by assay manufacturers do not fully recognize such pattern. Aims:. In this study, we aimed to establish a set of age- and sex-specific RIs for serum NT-proBNP in healthy adults from Northeast China. Methods:. Healthy adult subjects (20 to ≤95 years old) were recruited from the physical examination center at a teaching hospital during a period from March 2020 to July 2020. Serum NT-proBNP concentration was measured using the VITROS 5600 Integrated System with a chemiluminescence method. RIs were calculated based on the EP28-A3c guidelines by the Clinical and Laboratory Standards Institute. A generalized linear model was performed to factors that were associated with NT-proBNP level. Results:. The final analysis included 2,183 subjects (1,074 men and 1,109 women, mean age 54.2 ± 19.5 years). Serum NT-proBNP level increased with advancing age (20 to

Abstract Pulmonary arterial hypertension (PAH) prevalence is increasing worldwide, and the prognosis is poor with 5‐year survival

Herein, we define the role of ferroptosis in the pathogenesis of diabetic cardiomyopathy (DCM) by examining the expression of key regulators of ferroptosis in mice with DCM and a new ex vivo DCM model. Advanced glycation end-products (AGEs), an important pathogenic factor of DCM, were found to induce ferroptosis in engineered cardiac tissues (ECTs), as reflected through increased levels of Ptgs2 and lipid peroxides and decreased ferritin and SLC7A11 levels. Typical morphological changes of ferroptosis in cardiomyocytes were observed using transmission electron microscopy. Inhibition of ferroptosis with ferrostatin-1 and deferoxamine prevented AGE-induced ECT remodeling and dysfunction. Ferroptosis was also evidenced in the heart of type 2 diabetic mice with DCM. Inhibition of ferroptosis by liproxstatin-1 prevented the development of diastolic dysfunction at 3 months after the onset of diabetes. Nuclear factor erythroid 2-related factor 2 (NRF2) activated by sulforaphane inhibited cardiac cell ferroptosis in both AGE-treated ECTs and hearts of DCM mice by upregulating ferritin and SLC7A11 levels. The protective effect of sulforaphane on ferroptosis was AMP-activated protein kinase (AMPK)-dependent. These findings suggest that ferroptosis plays an essential role in the pathogenesis of DCM; sulforaphane prevents ferroptosis and associated pathogenesis via AMPK-mediated NRF2 activation. This suggests a feasible therapeutic approach with sulforaphane to clinically prevent ferroptosis and DCM.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of the coronavirus disease 2019 (COVID-19), has caused more than 179 million infections and 3.8 million deaths worldwide. Global health authorities working on the COVID-19 outbreak continue to explore methods to reduce the rate of its transmission to healthy individuals. Treatment protocols thus far have focused on social distancing and masking, treatment with antivirals early in infection, and steroids to reduce the inflammatory response. An alternative approach is therapy with low dose radiation (LDR), which has several advantages compared to the current drugs and medicines. To date more than 10 case reports and pilot clinical trial preliminary outcome are available from different countries. These reports cover a wide range of patient conditions and LDR treatment strategies. Although one report showed the failure to observe the improvement of COVID-19 patients after LDR therapy, the majority showed some clinical improvement, and demonstrated the safety of LDR for COVID-19 patients, particularly with 0.5 ​Gy. This review aims to summarize the potential rationales and mechanisms of LDR therapy for COVID-19 patients, and its current clinical status and potential use.

Abstract In the classic Cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway, downstream signals can control the production of type I interferon and nuclear factor kappa-light-chain-enhancer of activated B cells to promote the activation of pro-inflammatory molecules, which are mainly induced during antiviral responses. However, with progress in this area of research, studies focused on autoimmune diseases and chronic inflammatory conditions that may be relevant to cGAS–STING pathways have been conducted. This review mainly highlights the functions of the cGAS–STING pathway in chronic inflammatory diseases. Importantly, the cGAS–STING pathway has a major impact on lipid metabolism. Different research groups have confirmed that the cGAS–STING pathway plays an important role in the chronic inflammatory status in various organs. However, this pathway has not been studied in depth in diabetes and diabetes-related complications. Current research on the cGAS–STING pathway has shown that the targeted therapy of diseases that may be caused by inflammation via the cGAS–STING pathway has promising outcomes.

Abstract Cachexia is a progressive metabolic disorder characterized by the excessive depletion of adipose tissue. This hypermetabolic condition has catastrophic impacts on the survival and quality of life for patients suffering from critical illness. However, efficient therapies to prevent adipose expenditure have not been discovered. It has been established that the circadian clock plays an important role in modulating fat metabolic processes. Recently, an increasing number of studies had provided evidence showing that disrupted circadian rhythm leads to insulin resistance and obesity; however, studies analyzing the relationship between circadian misalignment and adipose tissue expenditure in cachexia are scarce. In the present review, we cover the involvement of the circadian clocks in the regulation of adipogenesis, lipid metabolism and thermogenesis as well as inflammation in white and brown adipose tissue. According to the present review, we conclude that circadian clock disruption is associated with lipid metabolism imbalance and elevated adipose tissue inflammation. Moreover, under cachexia conditions, lipid synthesis and storage processes lost rhythm and decreased, while lipolysis and thermogenesis activities remained high for 24 h. Therefore, disordered circadian clock may be responsible for fat expenditure in cachexia by adversely influencing lipid synthesis/ storage/lipolysis/utilization. Further study needs to be performed to explore the direct interaction between circadian clock and fat expenditure in cachexia, it will likely provide potential efficient drugs for the treatment of fat expenditure in cachexia.

Activation of the alternative pathway (AP) of complement is thought to play an important role in Immunoglobin A nephropathy (IgAN). Our previous study showed that rs4151657 within the complement factor B (CFB) gene increased the risk of IgAN. The protein encoded by the CFB gene is an initial factor that promotes AP activation. The aim of this study was to investigate whether other variants of CFB confer susceptibility to IgAN and elucidate their potential roles in AP activation. A total of 1,350 patients with IgAN and 1,420 healthy controls were enrolled and five tag single-nucleotide polymorphisms were selected for genotyping. The levels of key AP components, such as CFB, complement factor H and complement split product C3a, were measured by enzyme-linked immunosorbent assay. Molecular docking and molecular dynamic simulation were carried out to characterize the mutation of residues in the protein structure and the dynamic properties of wide type and mutation models of CFB protein. The allele-specific effect on CFB expression and its binding affinity to C3b were investigated through cell transfection and surface plasmon resonance analysis, respectively. We found that rs12614 significantly reduced the risk of IgAN (OR = 0.69, 95% CI = 0.52–0.91, P = 0.009), and the rs12614-T (R32W mutation) was correlated with lower CFB levels, higher serum C3 level, and less mesangial C3 deposition in patients with IgAN. The structural model showed that the R32W mutation reduced the structural stability of CFB protein. Furthermore, in vitro study revealed that rs12614-T decreased the expression of CFB and reduced its binding affinity to C3b by four-fold compared with rs12614-C. In conclusion, the rs12614-T in CFB was associated with low risk of IgAN probably by attenuating AP activation.

Endothelial progenitor cells (EPCs) are reduced in number and impaired in function in diabetic patients. Whether and how Nrf2 regulates the function of diabetic EPCs remains unclear. In this study, we found that the expression of Nrf2 and its downstream genes were decreased in EPCs from both diabetic patients and db/db mice. Survival ability and angiogenic function of EPCs from diabetic patients and db/db mice also were impaired. Gain- and loss-of-function studies, respectively, showed that knockdown of Nrf2 increased apoptosis and impaired tube formation in EPCs from healthy donors and wild-type mice, while Nrf2 overexpression decreased apoptosis and rescued tube formation in EPCs from diabetic patients and db/db mice. Additionally, proangiogenic function of Nrf2-manipulated mouse EPCs was validated in db/db mice with hind limb ischemia. Mechanistic studies demonstrated that diabetes induced mitochondrial fragmentation and dysfunction of EPCs by dysregulating the abundance of proteins controlling mitochondrial dynamics; upregulating Nrf2 expression attenuated diabetes-induced mitochondrial fragmentation and dysfunction and rectified the abundance of proteins controlling mitochondrial dynamics. Further RNA-sequencing analysis demonstrated that Nrf2 specifically upregulated the transcription of isocitrate dehydrogenase 2 (IDH2), a key enzyme regulating tricarboxylic acid cycle and mitochondrial function. Overexpression of IDH2 rectified Nrf2 knockdown- or diabetes-induced mitochondrial fragmentation and EPC dysfunction. In a therapeutic approach, supplementation of an Nrf2 activator sulforaphane enhanced angiogenesis and blood perfusion recovery in db/db mice with hind limb ischemia. Collectively, these findings indicate that Nrf2 is a potential therapeutic target for improving diabetic EPC function. Thus, elevating Nrf2 expression enhances EPC resistance to diabetes-induced oxidative damage and improves therapeutic efficacy of EPCs in treating diabetic limb ischemia likely via transcriptional upregulating IDH2 expression and improving mitochondrial function of diabetic EPCs.

Many landslides are triggered by excess precipitation. In the eastern part of China, landslides caused by extreme rainfall from typhoons in the monsoon season are the main geomorphological process with catastrophic impacts on society and the environment. In this study, Wenzhou City in eastern China was taken as the study area, and we compiled a detailed inventory of rainfall-triggered landslides between 1999 and 2016. The developmental characteristics of these landslides were determined with an emphasis on temporo-spatial distribution. The results showed that most of the landslides were located in the mountainous area of the western part of Wenzhou City. Landslides triggered by typhoon rainfall were commonly concentrated in a short period from July to September, when more than 70% of the landslides occurred. The landslides in this region were mainly of the debris-flow type, most of which were on a small scale, but had severe effects because of large elevation differences and long runout distances. Because the precipitation in typhoon events was commonly extreme, the initiation area of most landslides coincided with the region of highest hourly precipitation. Our results can provide reference data and guidelines for developing an early warning system for landslides and risk reduction in the study area.

Alternative splicing is pervasive in mammalian genomes and involved in embryo development, whereas research on crosstalk of alternative splicing and embryo development was largely restricted to mouse and human and the alternative splicing regulation during embryogenesis in zebrafish remained unclear. We constructed the alternative splicing atlas at 18 time-course stages covering maternal-to-zygotic transition, gastrulation, somitogenesis, pharyngula stages, and post-fertilization in zebrafish. The differential alternative splicing events between different developmental stages were detected. The results indicated that abundance alternative splicing and differential alternative splicing events are dynamically changed and remarkably abundant during the maternal-to-zygotic transition process. Based on gene expression profiles, we found splicing factors are expressed with specificity of developmental stage and largely expressed during the maternal-to-zygotic transition process. The better performance of cluster analysis was achieved based on the inclusion level of alternative splicing. The biological function analysis uncovered the important roles of alternative splicing during embryogenesis. The identification of isoform switches of alternative splicing provided a new insight into mining the regulated mechanism of transcript isoforms, which always is hidden by gene expression. In conclusion, we inferred that alternative splicing activation is synchronized with zygotic genome activation and discovered that alternative splicing is coupled with transcription during embryo development in zebrafish. We also unveiled that the temporal expression dynamics of splicing factors during embryo development, especially co-orthologous splicing factors. Furthermore, we proposed that the inclusion level of alternative splicing events can be employed for cluster analysis as a novel parameter. This work will provide a deeper insight into the regulation of alternative splicing during embryogenesis in zebrafish.

Both obesity and diabetes are global health threats due to their high risk of developing different complications [...]

Studying vegetation change and its interaction with climate change is essential for regional ecological protection. Previous studies have demonstrated the impact of climate change on regional vegetation in South America; however, studies addressing the fragile ecological environment in Argentina are limited. Therefore, we assessed the vegetation dynamics and their climatic feedback in five administrative regions of Argentina, using correlation analysis and multiple regression analysis methods. The Normalized Difference Vegetation Index 3rd generation (NDVI3g) from Global Inventory Monitoring and Modeling Studies (GIMMS) and climatic data from the Famine Early Warning Systems Network (FEWS NET) Land Data Assimilation System (FLDAS) were processed. The NDVI of the 1982–2015 period in Argentina showed a downward trend, varying from −1.75 to 0.69/decade. The NDVI in Northeast Argentina (NEA), Northwest Argentina (NWA), Pampas, and Patagonia significantly decreased. Precipitation was negatively correlated with the NDVI in western Patagonia, whereas temperature and solar radiation were positively correlated with the NDVI. Extreme precipitation and drought were essential causes of vegetation loss in Patagonia. The temperature (73.09%), precipitation (64.02%), and solar radiation (73.27%) in Pampas, Cuyo, NEA, and NWA were positively correlated with the NDVI. However, deforestation and farming and pastoral activities have caused vegetation destruction in Pampas, NEA, and NWA. Environmental protection policies and deforestation regulations should be introduced to protect the ecological environment. The results of this study clarify the reasons for the vegetation change in Argentina and provide a theoretical reference for dealing with climate change.

In this study, three mesoporous-activated crab shell biochars were prepared by carbonation and chemical activation with KOH (K−CSB), H3PO4 (P−CSB), and KMnO4 (M−CSB) to evaluate their tetracycline (TC) adsorption capacities. Characterization by SEM and a porosity analysis revealed that the K−CSB, P−CSB, and M−CSB possessed a puffy, mesoporous structure, with K−CSB exhibiting a larger specific surface area (1738 m2/g). FT-IR analysis revealed that abundant, surface ox-containing functional groups possessed by K−CSB, P−CSB, and M−CSB, such as −OH, C−O, and C=O, enhanced adsorption for TC, thereby enhancing their adsorption efficiency for TC. The maximum TC adsorption capacities of the K−CSB, P−CSB, and M−CSB were 380.92, 331.53, and 281.38 mg/g, respectively. The adsorption isotherms and kinetics data of the three TC adsorbents fit the Langmuir and pseudo-second-order model. The adsorption mechanism involved aperture filling, hydrogen bonding, electrostatic action, π-π EDA action, and complexation. As a low-cost and highly effective adsorbent for antibiotic wastewater treatment, activated crab shell biochar has enormous application potential.

As an environmental pollutant, cadmium (Cd) has been widely reported to induce male infertility due to its gonadotoxicity. However, the specific mechanism of Cd-induced testicular damage remains unclear. We investigated whether Cd causes testicular injury through ferroptosis. Male C57BL/6 J mice were exposed to 0, 0.5, or 5 ppm Cd via drinking water, starting in utero, and continuing through 24 weeks post-weaning. The results showed that Cd accumulated in the testes in a dose-dependent manner. Cd exposure at a concentration of 5 ppm, but not 0.5 ppm, caused a mass loss and detachment of germ cells, as well as a decreased meiotic index and testis weight. Exposure to 5 ppm Cd caused iron accumulation, increased levels of malondialdehyde (MDA) and nitro tyrosine (3-NT), and decreased expression of Nrf2, HO-1 and SOD2. We also found that exposure to 5 ppm Cd significantly decreased the expression of SLC7A11, a marker of ferroptosis in mice, along with the expression of SLC40A1 mRNA and ferritin heavy chain (FTH) protein, whereas there was no obvious change in the mRNA expression of Tfrc, ZIP8, ZIP14, and NCOA4. These findings indicate that 5 ppm Cd exposure increased testicular ferroptosis, which may be attributed to the reduction of stored iron export.

The effects of exposure to the environmental toxicant cadmium, in combination with obesity, on the metal content in mouse testis were evaluated. Starting in utero and continuing through to 10 or 24 weeks post-weaning, male mice were exposed to cadmium (0, 0.5 or 5 ppm), and fed either a low (LFD) or high fat diet (HFD) post-weaning. Testicular levels of cadmium and essential metals were determined 10 and 24 weeks post-weaning by ICP-MS. Similar to what has been previously observed in the liver, kidney, heart and brain, significant levels of cadmium accumulated in the testis under all exposure conditions. Additionally, HFD-fed animals accumulated more cadmium than did their LFD-treated counterparts. Both treatments affected essential metal homeostasis in the testis. These findings suggest that cadmium and obesity may compromise the reproductive potential in the male mouse by disrupting essential metal levels.