There is considerable interest in delineating the molecular mechanisms of action of transforming growth factor-β (TGF-β), considered as central player in a plethora of human conditions, including cancer, fibrosis and autoimmune disease. TGF-β elicits its biological effects through membrane bound serine/threonine kinase receptors which transmit their signals via downstream signalling molecules, SMADs, which regulate the transcription of target genes in collaboration with various co-activators and co-repressors. Until now, therapeutic strategy for primary Sjӧgren’s syndrome (pSS) has been focused on inflammation, but, recently, the involvement of TGF-β/SMADs signalling has been demonstrated in pSS, although TGFβ family members seems to have ambiguous effects on the function of pSS salivary glands. Based on these premises, this review highlights recent advances in unravelling the molecular basis for the multi-faceted functions of TGF-β in pSS that are dictated by orchestrations of SMADs, and describe TGF-β/SMADs value as both disease markers and/or therapeutic target for pSS.

Meprin α is a zinc metalloproteinase (metzincin) that has been implicated in multiple diseases, including fibrosis and cancers. It has proven difficult to find small molecules that are capable of selectively inhibiting meprin α, or its close relative meprin β, over numerous other metzincins which, if inhibited, would elicit unwanted effects. We recently identified possible molecular starting points for meprin α-specific inhibition through an HTS effort (see part I, preceding paper). In part II we report the optimization of a potent and selective hydroxamic acid meprin α inhibitor probe which may help define the therapeutic potential for small molecule meprin α inhibition and spur further drug discovery efforts in the area of zinc metalloproteinase inhibition.

Tenascin C (TNC) is an element of the extracellular matrix (ECM) of various tissues, including the skin, and is involved in modulating ECM integrity and cell physiology. Although skin aging is apparently associated with changes in the ECM, little is known about the role of TNC in skin aging. Here we found that Tnc mRNA level was significantly reduced in the skin tissues of aged mice compared with young mice, consistent with reduced TNC protein expression in aged human skin. TNC-large (TNC-L; 330-kDa) and -small (TNC-S; 240-kDa) polypeptides were observed in conditional media from primary dermal fibroblasts. Both recombinant TNC polypeptides, corresponding to TNC-L and TNC-S, increased the expression of type I collagen and reduced the expression of matrix metalloproteinase-1 in fibroblasts. Treatment of fibroblasts with a recombinant TNC polypeptide, corresponding to TNC-L, induced phosphorylation of SMAD2 and SMAD3. TNC increased the level of TGF-β1 mRNA and upregulated the expression of type I collagen by activating the TGF-β signaling pathway. In addition, TNC also promoted the expression of type I collagen in fibroblasts embedded in a three-dimensional collagen matrix. Our findings suggest that TNC contributes to the integrity of ECM in young skin and to prevention of skin aging.

In this paper, the lamellar structural evolution and microvoids variations of β-iPP during the processing of two different stretching methods, sequential biaxial stretching and simultaneous biaxial stretching, were investigated in detail. It was found that different stretching methods led to significantly different lamellae deformation modes, and the microporous membranes obtained from the simultaneous biaxial stretching exhibited better mechanical properties. For the sequential biaxial stretching, abundant coarse fibers originated from the tight accumulation of the lamellae parallel to the longitudinal stretching direction, whereas the lamellae perpendicular to the stretching direction were easily deformed and separated. Those coarse fibers were difficult to be separated to form micropores during the subsequent transverse stretching process, resulting in a poor micropores distribution. However, for the simultaneous biaxial stretching, the β crystal had the same deformation mode, that is, the lamellae distributed in different directions were all destroyed, forming abundant microvoids and little coarse fibers formation.

GbtXyl43A, a β-xylosidase that is isolated from Geobacillus thermoleovorans IT-08 and grouped in GH43 family. The substitution of 121Asp residue with Asn in GbtXyl43A caused decrease the enzyme activity. The aim of this study, determine the kinetic characteristics of wild-type GbtXyl43A and D121N variant using Vmax, KM, kcat, and kcat/KM. These parameters indicated catalytic mechanism of GbtXyl43A and its derivative. All of them were produced in Escherichia coli BL21 star. The purification of wild-type GbtXyl43A using affinity chromatography, but D121N variant also required anion-exchange chromatography. The specific activity of wild-type GbtXyl43A and D121N variant were 0.471 U mg-1 in purity level 55,44 and 0.012 U mg-1 in purity level 2,407, respectively. Both enzymes had same molecular weight, ~58 kDa. The kinetic parameters of wild-type GbtXyl43A were KM: 2.845 mM, kcat: 0.033 s-1, Vmax: 0.0033 mM min-1and kcat/KM: 0.0115 s-1mM-1. Furthermore, the KM, kcat, Vmax, and kcat/KM values of D121N variant were 4.565 mM, 1.01 × 10-4 mM min-1, 0.140 × 10-4 s-1, and 0.0307 s-1mM-1, respectively. The KM value of the D121N variant was higher than its wild type and showed the affinity of D121N variant was lower than GbtXyl43A

COVID-19 disease, caused by the SARS-CoV2 virus, is a potentially fatal disease that represents a serious public health and economic problem worldwide. The SARS-CoV2 virus infects the lower respiratory tract and can cause pneumonia in humans. ARDS is the leading cause of death in COVID-19 disease. One of the main characteristics of ARDS is the cytokine storm, an uncontrolled systemic inflammatory response resulting from the release of pro-inflammatory cytokines and chemokines and growth factors, by immune cells. The other important aspect of the disease is represented by the involvement of the vascular organ that undergoes endothelitis. Hyperinflammation and endothelitis contribute in various ways to trigger coagulation disorders with diffuse micro thrombotic and thromboembolic phenomena. Lastly, multiple organ failure may occur (MOF). Since so far there is no approved treatment, there is an urgent need to reposition known treatments, considered safe, to be included in trials. Naturally produced interferons represent the body's first line of defense against viruses. Pharmacological forms, obtained by means of genetic recombination techniques, have long been approved and used to treat numerous pathologies. Interferons are divided into three families, within which some subfamilies are distinguishable. Only IFN-II comprises a single isoform which has completely different aspects and functions. The IFN I and III, however, each comprise different subfamilies (17 subfamilies the IFN-I and 4 subfamilies the IFN-III), share many aspects, representing the body's first antiviral response, but play different roles. The use of IFNs has been studied in two severe hCoV (Human Coronavirus) diseases, closely related to COVID-19 disease, such as SARS and MERS. Numerous in vitro and in vivo studies have been conducted, often in combination with other antivirals. The results have been controversial. The positive results in vitro and in experimental animals were often not replicable in humans. The possible positioning of these molecules in the right window of therapeutic opportunity requires that the complex dialogue between IFN, inflammasome, cytokines, pro-inflammatory chemokines, growth factors and barrier function be shed light.

A derivative series of 3,4-dimethoxy-β-nitrostyrene were synthesized and identified including new compound 6. The effect of antimicrobial activity of 3,4-alkyloxy modification of β-nitrostyrene was investigated. A molecular docking was also performed to obtain information about their interactions with Protein Tyrosine Phosphatase 1B (PTP1B). PTP1B containing cysteine 215 and arginine 221 as essential active residues plays a key role in signaling pathways that regulate various cell functions of microorganisms, which also act as negative regulator in signaling pathways of insulin that are involved in type 2 diabetes and other metabolic diseases. Compound 5 and 6 were the most potent as fragment of PTP1B inhibitor based on molecular docking, but compound 5 was more effective against Candida albicans. These compounds interact with serine 216 and arginine 221 residues. However, further research is needed to investigate their potential medicinal use.

The recognition of (1→3)-β-D-glucans (BGs) by β-1,3-D-glucan recognition protein (BGRP) found in invertebrates plays a significant role in the activation of toll pathway and pro-phenol oxidase system in insect host defense against fungal invasion. To examine the structural diversity of BGs in BGRP interaction, the binding specificity of BGRPs cloned from four different insectswas characterized using ELISA. Recombinant BGRPs expressed as Fc-fusion proteins of human IgG1 bound to solid phase BGs. Because of the binding specificities, the BGRPs were categorized into two different ultrastructure- binding characters. The BGRPs from Silkworm and Indian meal moth bound to BGs containing triple-helical structure. Other BGRPs from red flour beetle and yellow mealworm beetle showed no binding to triple-helical BGs, but to alkaline-treated BGs, which have partially opened helical conformation. These evidences suggest that the innate immune system distinguishes different BG conformations and it is equipped for the diversity of BG structures.

Thienopyrimidines are a versatile group of compounds that contain a biologically active pharmacophore and reported to have anticancer efficacy in vitro. Here, we report for the first time, that thieno[3,2-d]pyrimidine - based compounds, designated the RP series, have efficacy in prostate cancer cells. The lead compound, RP-010, was efficacious in PC3 and DU-145 prostate cancer (PC) cells (IC50< 1µM). The cytotoxicity of RP-010 was significantly lower in normal cells. RP-010 (0.5, 1, 2, and 4 µM) arrested prostate cancer cells in the G2 phase of the cell cycle, induced mitotic catastrophe and apoptotic signaling in both PC cell lines. Mechanistic studies suggested that RP-010 (1 and 2 µM) inhibits the wingless-type MMTV (Wnt)/β-catenin signaling pathway, mainly by inducing β-catenin fragmentation, while down regulating important proteins in the pathway, i.e. LRP-6, DVL3, and c-Myc. Interestingly, RP-010 (1 and 2 µM) induced the nuclear translocation of the negative feedback proteins, Naked 1 and Naked 2, in the signaling pathway. In addition, RP-010 (0.5, 1, 2, and 4 µM) significantly decreased the migration and invasiveness of PC cells in vitro. Finally, RP-010 did not produce significant toxic effects in zebrafish at concentrations up to 6 µM. In conclusion, RP-10 is a promising anticancer compound in metastatic prostate cancer and did not produce overt toxicity in an in vivo zebrafish model. Future mechanistic and efficacy studies are needed in-vivo to optimize the lead compound RP-010 for clinical use.

Though Moracin D derived from Morus alba was known to have anti-inflammatory and antioxidant activities, the underlying antitumor mechanism of Moracin D was never unveiled so far. Thus, in the recent study, the apoptotic mechanism of Moracin D was elucidated in breast cancer cells. Herein, Moracin D exerted significant cytotoxicity in MDA-MB231 and MCF7 cells. Also, Moracin D increased sub G1 population, cleaved poly (ADP-ribose) polymerase (PARP) and attenuated the expression of pro-cysteine aspartyl-specific protease (procaspase 3), c-Myc, cyclin D1, B-cell lymphoma 2 (Bcl-2),and X-linked inhibitor of apoptosis protein (XIAP) in MDA-MB231 cells. Of note, Moracin D reduced expression of Forkhead box M1 (FOXM1), β-catenin, Wnt3a, and upregulated glycogen synthase kinase 3 beta (GSK 3β) on Tyr216 along with disturbed binding of FOXM1 with β-catenin in MDA-MB-231 cells. Conversely, GSK3β inhibitor SB216763 reversed the apoptotic ability of Moracin D to reduce expression of FOXM1, β-catenin, pro-caspase3 and pro-PARP in MDA-MB-231 cells. Overall, these findings provide novel insight that Moracin D inhibits proliferation and induces apoptosis via suppression of Wnt3a/FOXM1/β-catenin signaling and activation of caspase and GSK3β

Recent interest in intestinal hormones has risen with the idea that they modulate glucose tolerance and food intake through a variety of mechanisms, and such hormones like peptide YY (PYY), ghrelin, glucagon-like peptide (GLP)-1 and 2, and cholecystokinin (CKK) are therefore excellent therapeutic candidates for the treatment of diabetes and obesity. Furthermore, in the recent years, multiple studies suggest that the microbiota is critically important for normal host functions, while impaired host microbiota interactions contribute to the pathogenesis of numerous common metabolic disorders. In this study, we considered the nutraceutical effects of β-glucans added to pasta at the concentration of 6g\100g. Ten participants have been recruited and hematochemical analyses and intestinal hormones tests have been performed before and after 30 days of pasta intake. Stool specimens have been studied for Lactobacillus Fermentum, Lactobacillus acidophilus, Lactobacillus salivarius, Bifidobacterium longum, and Enterococcus faecium presence before and after 30 days of nutritional intervention. After 30 days of regular intake of pasta enriched by β-glucans results have been evaluated. In conclusion, pasta prepared from barley flour enriched with β-glucans at 6% exhibit promising responses on glucose metabolism, on intestinal hormones responses and on microbiota modification.

The increasing use of Convolutional Neural Networks (CNN) has brought about a significant transformation in numerous fields, such as image categorization and identification. In the development of a CNN model for classifying images of sericea lespedeza (SL; Lespedeza cuneata) from weed images, four architectures were explored: CNN-Model Variant 1, CNN-Model Variant 2, VGG16, and ResNet50. The CNN-Model Variant 1 demonstrated 100 % validation accuracy, while Variant 2 achieved 90.78% validation accuracy. Pre-trained models, like VGG16 and ResNet50, were also analyzed. In contrast, ResNet50's steady learning pattern indicated potential for better generalization. A detailed evaluation of these models revealed that Variant 1 achieved a perfect score in precision, recall, and F1-score, indicating superior optimization and feature utilization. Variant 2 presented a balanced performance, with metrics between 86% and 93%. The VGG16 mirrored the behavior of Variant 2, both maintaining around 90% accuracy, but ResNet50's results revealed a conservative approach for class 0 predictions. Overall, Variant 1 stood out in performance, while both Variant 2 and VGG16 showed balanced results. The reliability of CNN model Variant 1 is highlighted by the significant accuracy percentages, which demonstrate its potential for practical implementation in agriculture. Smartphone application for the identification of SL in a field-based trial has shown promising results with an accuracy of 98%-99%. Using a CNN model with batch normalization has the potential to play a crucial role in redefining and optimizing the management of undesirable vegetation in the future.

In order to foster a more sustainable and eco-friendly trajectory for the construction industry, while concurrently mitigating environmental pollution and energy inefficiency, it is imperative to cultivate an environmentally conscious building and urban environment. Under the background of carbon peak and carbon neutrality, green building evaluation system (GBRS) has become a research hotspot in the field of green building. This paper systematically summarizes the current research progress based on GBRS, focuses on the current weight and indicators setting, analyzes it with Cite Space software, and puts forward its future development direction. The results show that the weight setting method of green building evaluation system is determined by multidimensional and multi-method. From the perspective of environment, society and economy, the scope of indicators setting is expanding. The green building evaluation system will play a guiding role in green building design, and the evaluation process will continue to be optimized and developed in the direction of intelligence and automation.

Background: Ankle fractures, comprising about 10% of musculoskeletal injuries, pose a significant healthcare burden with an increasing incidence, particularly among an aging population. This study focuses on isolated Danis-Weber type B fractures. Recent trends lean towards surgical intervention for anatomical restoration, quicker recovery, albeit with associated complications. This report aims to assess the safety and efficacy of NewClip narrow locking plate system with early weight bearing in treating isolated fibular fractures. Methods: The study includes patients with Danis-Weber type B fractures surgically treated with NewClip narrow locking plate system. Exclusions involved nondisplaced fractures, open fractures, or those requiring additional fixation.Results: Fifteen patients were enrolled in this study. Minor complications, including wound swelling, were observed in two cases. The Visual Analogue Scale (VAS) for pain exhibited a steady decline postoperatively, with almost complete resolution by the third month. At three months, the FAOS demonstrated excellent results, and final follow-up at twelve months revealed complete osseous healing without complications.Conclusions: The use of this type of plates in treating isolated fibular fractures with early weight bearing shows promising results in terms of fracture healing, pain resolution, and functional outcomes warranting further investigation with larger cohorts.

Abstract: Rural digital governance is an inevitable requirement to improve the efficiency of rural governance, and is also an important means to realize the modernization of rural governance. In the context of the digital rural development strategy, the index measurement system of rural digital governance level is built around five key governance areas of "digital economy, digital ecology, digital culture, digital people's livelihood, and digital government affairs". The entropy weight Topsis model is used to measure and evaluate the level of rural digital governance in 31 provinces in China in 2021. The results show that there is a large gap in the level of digital governance in China's counties and villages, and the level of each region presents a decreasing spatial distribution from "east - middle - west". In terms of digital economy, the eastern region has a high score and good development, while the central and western regions have poor development. In terms of digital ecology, only the eastern region is higher than the national average; In terms of digital culture, only the central region is higher than the national average; In terms of digital livelihood and digital government, the central and eastern regions are slightly higher than the national average; The top three provinces in overall scores are Zhejiang, Guangdong and Jiangsu.

Accurate weight measurement is pivotal for monitoring the growth and well-being of cattle. However, the conventional weighing process, which involves physically placing cattle on scales, is labor-intensive and distressing for the animals. Hence, the development of automated cattle weight prediction techniques assumes critical significance. This study proposes a weight prediction approach for Korean cattle using 3D segmentation-based feature extraction and regression machine learning techniques from incomplete 3D shapes acquired from real farm environments. In the initial phase, we generated mesh data of 3D Korean cattle shapes using a multiple-camera system. Subsequently, deep learning-based 3D segmentation with the PointNet network model was employed to segment two dominant parts of the cattle. From these segmented parts, three crucial dimensions of Korean cattle were extracted. Finally, we implemented five regression machine learning models (CatBoost regression, LightGBM, Polynomial regression, Random Forest regression, and XGBoost regression) for weight prediction. To validate our approach, we captured 270 Korean cattle in various poses, totaling 1190 poses of 270 cattle. The best result was achieved with mean absolute error (MAE) of 25.2 kg and mean absolute percent error (MAPE) of 5.81% using the random forest regression model.

A pilot study regarding the transplantation of 100 specimens of the critically endangered Pinna nobilis took place in summer of 2019 in Maliakos Gulf (Central Aegean, Greece). In this study we present the relationships between total height (HT, in cm), unburied length (UL, in cm), and shell width (SW, in cm) for P. nobilis and the relationship between HT and net weight (W, in g). Length-length relationships were all linear for all cases: r2 > 0.900), whereas the relationship between HT and W was exponential with the value of the exponent b being allometric. "Ecology, Conservation and Restoration of Threatened Animal"

(1) Background: This study aimed to evaluate whether the implementation of a modified blood sampling protocol, which focused on need-based laboratory testing and minimized venous sampling by replacing it with point-of-care testing (POCT) via capillary puncture, successfully reduced iatrogenic blood loss, incidence of anemia, and frequency of blood transfusion in extremely low birth weight infants (ELBWIs) without negatively affecting neonatal outcomes. (2) Methods: A retrospective analysis was conducted on 313 ELBWIs of gestational age (GA) between 23 and 28 weeks, born between 2013 and 2019. The infants were divided into two groups: before (period I) and after (period II) the implementation of the modified blood sampling protocol in January 2016. Propensity score matching was conducted to minimize selection bias. Clinical data, including the frequency and amount of blood sampling, frequency and volume of blood transfusion, and clinical characteristics, such as gestational age, birth weight, and neonatal outcome data, were collected and compared between the two groups. (3) Results: No significant differences in the GA or birth weight between the two periods were observed. The total sampling volume during a month after birth (16.7 ± 4.1 mL vs. 15.6 ± 4.4 mL, P=0.03) and total sampling volume during hospital days (51.4 ± 29.7 mL vs. 44.3 ± 27.5 mL, P=0.04) in period II were significantly lower than that in period I. There were no differences in the mortality or morbidity between the two periods. Although the transfusion frequency and amount did not have significant differences between the periods, we observed a positive correlation between the transfusion frequency and sampling volume (coefficient: 0.09, 95% CI: 0.08–0.11). (4) Conclusions: The modified blood sampling protocol effectively reduced the iatrogenic blood loss without negatively affecting the neonatal outcomes.

Metabolic and bariatric surgery (MBS) is the most effective long-term treatment for Class III obesity. Reduced dietary intake is considered a behavioral driver of post-surgical weight loss, but limited data have examined this association. Therefore, this study examined prospective, longitudinal relationships between dietary intake and weight loss over 24 months following Roux-en-Y Gastric Bypass and Sleeve Gastrectomy. Relationships between weight loss and dietary intake were examined using a validated 24-hour dietary recall method. Associations between total energy/macronutrient intake and weight loss outcomes were assessed at 12-, 18-, and 24-months following MBS, defining patients as “responders” and “suboptimal responders” according to the Reinhold criteria of 50% excess weight loss. Consistent with previous literature, 12-month responders and suboptimal responders showed significant associations between weight loss and dietary intake. Unlike previous work, this study revealed that many of these associations are no longer significant 24 months post-MBS, despite consistent weight loss trends. This study suggests a short-term signal between these dietary factors and weight loss outcomes 12 months post-MBS, consistent with previous observations. However, this signal does not persist beyond 12 months. These results are essential for interpreting and designing clinical studies measuring long-term post-surgical weight loss outcomes.

Background: Blood flow restriction training (BFRT) uses occlusion during low-intensity resistance training (&lt;50% of repetition maximum, 1RM) to reduce arterial blood flow and venous return, imposing greater metabolic stress but similar muscular hypertrophy and strength gains as high-intensity resistance training (HIRT). However, no study, to date, has incorporated BFRT in a collegiate strength and conditioning setting to assess ecological validity. We aimed to investigate the effects of adding 6-weeks of accessory BFRT or HIRT to NCAA Division III soccer players prescribed resistance training regimen on muscle strength and hypertrophy. Methods: Male and female (n=17) athletes were randomly assigned to complete biceps curls 2x/week under BFRT or control (HIRT), following the regularly scheduled strength training. Bicep strength (1RM) and circumference (BC) were assessed at weeks 0, 3, and 6. Results: In men, no significant interaction between time and condition was observed for BC (p=0.861), though condition (BFRT vs Control, p=0.025) and time (p=0.024) were significant. For 1RM, there was no significant interaction between time and condition (BFRT vs HIRT, p=0.067) or of condition (p=0.598), but there was a significant effect of time (p=0.004). In women, there was no significant interaction between time and condition (p=0.765) or of condition (p=0.971) on BC, but time was significant (p=0.045). For 1RM, there was no significant interaction between time and condition (p=0.227) or of condition (p=0.741), but time was (p=0.018). Conclusion: BFRT induced similar increases in muscle strength and hypertrophy as HIRT in soccer players, suggesting that BFRT could be incorporated into collegiate athlete training.

Currently, algae arouse a growing interest in the pharmaceutical and cosmetic area due to the fact that they have a great diversity of bioactive compounds with the potential for pharmacological, cosmetic, and nutraceutical applications. Many of these bioactive compounds are secondary metabolites whose amounts in the algae vary with varying environmental conditions. Free radicals and other active oxygen derivatives are recognized as a natural by-product of aerobic metabolism. However, reactive oxygen species directly participate in mechanisms related to various pathological states such as cancer, diabetes, atherosclerosis, Alzheimer's, and Parkinson's, among others. Diabetes mellitus (DM) is a metabolic disease resulting from changes in glucose metabolism and/or deficient production/action of insulin. This review has as its main objective to reveal the potential antioxidant and antidiabetic capacity of algae extracts.

(1) Background: Loss of weight is one of the practices which have been identified as key in reducing the risk of various forms of cancer. Therefore, this study is a systematic review and meta-analysis of studies related to the topic of loss of weight and risk of cancer and addresses the question, ‘does losing weight reduce the risk of cancer?’ Its purpose is to identify current high-quality evidence on such a question and synthesize such evidence before summarizing it given specific data attributes to improve decision-making processes on cancer management. (2) Methods: Research studies were identified from four main databases: PubMed, Science Direct, Google scholar, and Medline. A systematic review and meta-analysis of such studies were then conducted to reveal the most current evidence on the research topic. (3) Results: The studies showed that losing weight reduces cancer risk. Nonetheless, such intervention is not necessarily effective, especially in cases where patients may be at risk of developing cancer due to other risk factors. (4) Conclusions: The current study concludes that there is a need to implement effective interventions such as physical exercise, dietary restrictions, or both that can be effective in reducing weight to reduce the risk of cancer.

A significant number of research studies have focused on determining whether BMI influences various types of cancer. The findings of these studies showed that people have to manage their BMIs to decrease their risk of developing various types of cancer, one of which is ovarian cancer. A PRISMA guideline for systematic review and meta-analysis was used to identify 20 research studies related to the topic to establish the truth or falsity of the findings. Later, their findings were synthesized. The synthesis of the findings of such research articles suggests that overweight and obesity increase an individual’s risk of developing ovarian cancer and experiencing severe symptoms of the disease. In such a manner, the current research study can conclude that effective management of BMI is necessary for decreasing the prevalence and mortality rates associated with ovarian cancer.

According to known laws of physics, chronic positive mass balance is the actual etiology of obesity, not positive energy balance. The relevant physical law in terms of body mass regulation is the Law of Conservation of Mass, not the Law of Conservation of Energy. A recently proposed mass balance model (MBM) describes the temporal evolution of body weight and body composition under a wide variety of feeding experiments, and it seems to provide a highly accurate description of the very best experimental human feeding data. By shifting to a mass balance paradigm of obesity, a deeper understanding of this disease may follow in the near future. The purpose of this living review is to present the core issues of the upcoming paradigm shift as well as some practical applications related to the topic.

In order to solve the labor-intensive and time-consuming problem in the process of measuring yak body ruler and weight in yak breeding industry in Qinghai Province, a non-contact method for measuring yak body ruler and weight was proposed in this experiment, and key technologies based on semantic segmentation, binocular ranging and neural network algorithm were studied to boost the development of yak breeding industry in Qinghai Province. Main conclusions: (1) Study yak foreground image extraction, and implement yak foreground image extraction model based on U-net algorithm; select 2263 yak images for experiment, and verify that the accuracy of the model in yak image extraction is over 97%. (2) Develop an algorithm for estimating yak body ruler based on binocular vision, and use the extraction algorithm of yak body ruler related measurement points combined with depth image to estimate yak body ruler. The final test shows that the average estimation error of body height and body oblique length is 2.6%, and the average estimation error of chest depth is 5.94%. (3) Study the yak weight prediction model; select the body height, body oblique length and chest depth obtained by binocular vision to estimate the yak weight; use two algorithms to establish the yak weight prediction model, and verify that the average estimation error of the model for yak weight is 10.7% and 13.01% respectively.

Introduction: Leptin is a polypeptide hormone and in pregnancy it is secreted by the placenta and maternal and fetal adipose tissues. The expression of leptin and its specific receptors is observed in the uterine endometrium which indicates leptin involvement in the implantation process and embryonic/fetal development. Normal leptin production is a factor responsible for uncomplicated gestation, embryo development and fetal growth. Objective: To compare at delivery maternal serum and cord blood leptin concentrations in normal pregnancies and in pregnancies complicated by intrauterine growth restriction (IUGR). Material and methods: The study was performed in 25 pregnant women with isolated IUGR diagnosed by ultrasonography (study subjects) and in 194 pregnant women without any comorbid health conditions (controls). Leptin concentrations in maternal serum and in cord blood samples collected at delivery were measured by ELISA and subsequently analyzed by maternal Body Mass Index (BMI), mode of delivery, and infant gender and birth weight. For comparative analyses of normally distributed variables, parametric tests were used, i.e. the Student-t to test the assumption of homogeneity or non-homogeneity of variance and a One-Way ANOVA when more than two groups were compared. The non-parametric Mann-Whitney test was used when the distribution was not normal. The Pearson correlation coefficient was calculated to assess the correlation between normally distributed variables (p<0.05). Results: In pregnancies complicated by IUGR, the mean maternal serum leptin concentration at delivery was significantly higher (52.73 ± 30.49 ng/mL) than in normal pregnancies (37.17 ± 28.07 ng/mL) (p=0.01). The mean cord blood leptin concentration in pregnancies complicated by IUGR was 7.97 ± 4.46 ng/mL and significantly lower than in normal pregnancies (14.78 ± 15.97 ng/mL) (p=0.04). In normal pregnancies, but not in pregnancies complicated by IUGR, a statistically significant correlation was established between maternal serum leptin concentrations and maternal BMI at delivery (r=0,22; p=0.00). No statistically significant correlation was found between cord blood leptin concentrations and maternal BMI in either study subjects or controls. In normal pregnancies, but not in pregnancies complicated by IUGR, a strong correlation was observed between cord blood leptin concentrations and birth weight (r=0,23; p=0.00). In both study subjects and controls, there were no correlations between leptin concentrations in maternal serum and cord blood and infant gender and mode of delivery. Conclusions: Elevated maternal blood leptin concentrations in pregnancies complicated by IUGR may indicate a significant adverse effect of elevated leptin on fetal growth. Enhanced leptin production by the placenta suggests leptin as a candidate marker of placental insufficiency. The differences in leptin concentrations, measured in maternal serum and in cord blood, between the study subjects and controls suggest that deregulated leptin levels may increase the risk of obstetric complications associated with placental insufficiency.

The inhibition impacts of 1,10-Phenanthroline-5,6-diamine (PTDA) on mild steel in 1 M HCl solution were investigated through weight loss method. The inhibition efficiencies of PTDA increase with increase in PTDA concentration at the temperature 303. Weight loss method indicate that PTDA is an excellent inhibitor the inhibition efficiency of 81.5% at the maximum PTDA concentration of 0.5 g/L at the temperature 303K.

This randomized control trial aims to test the hypothesis that twice-daily nurse-administered saline enema(SE) is comparable to physician-administrated SE in very low birth weight infants (VLBW) with meconium obstruction of prematurity (MOP). MOP is defined as no bowel opening for 48 h, and treatment failure is defined as the need for additional intervention and safety. Twice-daily SE was administered by accredited nurses, surgeons/neonatologists using standardized protocols. The outcomes were comparability of nurse to physician-administered SE in terms of frequency of administration, catheter insertion length and volume of enema, daily maximum meconium output, and treatment failure, defined as the need for additional intervention. Safety outcomes were evaluated. Twenty-eight infants were managed with SE. 389 SE were administered, 96 and 293 in 750-999g and 1000-1500g birth weight groups, respectively. Nurses administered 72.9% and 81.5% of SE in 750-999g and 1000-1500g birth weight groups, respectively. Physicians performed the rest of the SE. Daily meconium output was comparable in nurse and physician-administered SE in both groups. There were no treatment failures or adverse events in both SE group. SE administered by nurses was found to be comparable in terms of safety, efficacy, and frequency of administration to that of physician-administered SE.

This article focuses on the current state-of-the-art in the area of cellular and molecular biotechnology for over-production of clinically relevant therapeutic growth factors and how the technology can be used for the treatment of osteoarthritis (OA). Transfected and irradiated protein packaging cell lines may be used as “cellular factories” for large-scale production of therapeutic proteins and pro-anabolic growth factors, particularly in the context of cartilage matrix regeneration. We discuss the potential for new innovations in regenerative medicine for degenerative diseases of synovial joints using mammalian protein production platforms, specifically protein packaging cell lines, for over-producing growth factors for cartilage tissue regeneration and give recent examples. Mammalian protein production platforms that incorporate protein packaging cell lines are superior to bacterial expression systems and are likely to have a significant impact on the development of new biological therapies for treating focal cartilage defects and more generally for the treatment of degenerative joint diseases such as OA.

Permeability has an important effect on drug absorption. In this study, the effect of different concentrations of sodium sulfobutyl ether-β-cyclodextrin (SBE-β-CD) on the absorption of ranitidine was investigated to examine the mechanism of permeability changes. The results of parallel artificial membrane permeability assay (PAMPA) showed that increasing the concentration of sodium sulfobutyl ether-β-cyclodextrin, 0, 0.12% (w/v), 0.36% (w/v) and 3.6% (w/v), respectively, the apparent permeability coefficient of ranitidine decreased to 4.62×10-5 , 4.5×10-5 , 3.61×10-5 and 1.08×10-5 in Caco-2 cells, respectively. The same results were obtained from oral pharmacokinetic study in rats; Further studies indicated that SBE-β-CD significantly increased the zeta potential of ranitidine. SBE-β-CD interacted with ranitidine charges to form a complex that reduced ranitidine permeability, and SBE-β-CD should be chosen with caution for drugs with poor permeability.

Lipopolysaccharides are a type of polysaccharide mainly present in the bacterial outer membrane of Gram-negative bacteria. Recent studies have revealed that lipopolysaccharides contribute to the immune response of the host by functioning as a cancer antigen. We retrospectively recruited 198 patients with gastric cancer who underwent surgery. The presence of lipopolysaccharides was determined using immunohistochemical staining, with the intensity score indicating positivity. The relationship between lipopolysaccharides and CD8, PD-L1, TGFBI (a representative downstream gene of TGF-β signaling), E-cadherin, and claudin-4 (epithelial–mesenchymal transition markers) was also investigated. Thereafter, we identified 20 patients with advanced gastric cancer receiving nivolumab and investigated the relationship between lipopolysaccharides and nivolumab sensitivity. After staining for lipopolysaccharides in the nucleus of cancer cells, 150 negative (75.8%) and 48 positive cases (24.2%) were found. The lipopolysaccharide-positive group showed increased cancer stromal TGFBI expression (p &lt; 0.0001) and PD-L1 expression in cancer cells (p = 0.0029). Lipopolysaccharide positivity was significantly correlated with decreased E-cadherin expression (p = 0.0055) and claudin-4 expression (p = 0.029); however, no significant correlation was found between lipopolysaccharide expression and overall survival rate (p = 0.71). Among cases receiving nivolumab, the lipopolysaccharide-negative and -positive groups had a disease control rate of 66.7% and 11.8%, respectively (p = 0.049). Lipopolysaccharide positivity was associated with TGF-β signaling and epithelial–mesenchymal transition and was considered to promote therapeutic resistance to nivolumab.

Leukemia, characterized by abnormal blood cell proliferation, remains a significant challenge in cancer treatment. Thymoquinone (TQ), a bioactive compound derived from black seed, has demonstrated anticancer properties, including telomerase inhibition and induction of apoptosis. However, TQ's poor solubility and limited bioavailability hinder its clinical application. This study explores the use of SBE-β-CD, a cyclodextrin derivative, to enhance the solubility and stability of TQ for leukemia treatment. SBE-β-CD offers low hemolytic activity and has been successfully employed in controlled drug release systems. The study investigates the formation of inclusion complexes between TQ and SBE-β-CD and assesses their effects on leukemia cell growth. Results indicate that the TQ/SBE-β-CD complex exhibits improved solubility and enhanced cytotoxic effects compared to TQ alone, suggesting the potential of SBE-β-CD as a drug delivery system for TQ. Annexin V-FITC tests demonstrate increased apoptosis and reduced telomerase activity in leukemia cells treated with TQ/SBE-β-CD, supporting its anti-leukemic potential. Molecular docking analysis reveals a strong binding affinity between TQ and telomerase. However, further research is needed to optimize the apoptotic effects and minimize necrosis induction. In conclusion, TQ/SBE-β-CD shows promise as a novel strategy for leukemia treatment by targeting telomerase and enhancing the cytotoxic effects of TQ, offering a potential solution to overcome the limitations of TQ's poor solubility and bioavailability.

Background: For the treatment of bone defects, biodegradable compressive biomaterials are needed as a substitute, which degrade at the same rate as the bone regenerates. In this study, the compressive strength of CPC ceramics (with a layer thickness of more than 12 layers) should be compared with sintered ceramics. Methods: Round scaffolds with 20, 25, 30 and 45 layers were 3D printed the 3D Bioplotter, solidified in a water-saturated atmosphere for 3 days and then tested for compressive strength together with a sintered ceramic using a Zwick universal testing machine. Results: The 3D printed scaffolds are more compressive at 41.56 ± 7.12 MPa than the sintered ceramic at 24.16 ± 4.44. Conclusions: The round geometry sintered ceramics approach or exceed the upper limit of the compressive strength of cancellous bone in the direction of compacta (depending on the author).

TGF-ꞵ signaling is a vital regulator for maintaining articular cartilage homeostasis. Runx transcription factors, downstream targets of TGF-ꞵ signaling, have been studied in the context of osteoarthritis (OA). Although Runx partner core binding factor β (Cbfβ) is known to play a pivotal role in chondrocyte and osteoblast differentiation, the role of Cbfβ in maintaining articular cartilage remains obscure. This study investigated Cbfβ as a novel anabolic modulator of TGF-ꞵsignaling and determined its role in articular cartilage homeostasis. Cbfβ significantly decreased in aged mouse articular cartilage and human OA cartilage. Articular chondrocyte-specific Cbfb-deficient mice (Cbfb△ac/△ac) exhibited early cartilage degeneration at 20 weeks old and developed OA at 12 months old. Cbfb△ac/△ac mice showed enhanced OA progression under the surgical-induced mice OA model. Mechanistically, forced expression of Cbfβ rescued Col2α1 and Runx1 expression in Cbfβ-deficient chondrocytes. TGF-ꞵ1-mediated Col2α1 expression failed despite the pSmad3 activation under TGF-ꞵ1 treatment in Cbfβ-deficient chondrocytes. Cbfβ protected Runx1 from proteasomal degradation through Cbfβ/Runx1 complex formation. These results indicate that Cbfβ is a novel anabolic regulator for cartilage homeostasis, suggesting that Cbfβ could protect OA development by maintaining the integrity of the TGF-ꞵ1 signaling pathway in articular cartilage.

Mechanochemical production of copper (II) isonicotinate Metal-Organic Framework ([Cu (INA)2]-MOF) and its modified magnetic iron composite ([Cu (INA)2]-MOF@Fe3O4]) allowed for the adsorptive removal of Terbutaline from water. A variety of characterization techniques, including Fourier, transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and scanning electron microscopy (SEM), were used to elucidate the distinct chemical and morphological features of the two advanced materials. The optimal adsorption conditions were determined by investigating a wide range of adsorption-related variables, including contact time, initial Terbutaline concentration, adsorbent dosages pH, and temperature. The chemistry involved in the adsorption process between the adsorbents and the adsorbate molecules was evaluated using the best-fitting models, such as kinetics, isotherms, and thermodynamics, and the regeneration study was performed to evaluate the adsorbents' reusability. Incredibly maximum adsorption capacities (Qmax) of 1667 and 2500 mg L-1 were attained within 40 minutes under alkaline pH 11 by the [Cu (INA)2]-MOF and the [Cu (INA)2]-MOF@Fe3O4, respectively. The adsorbents have been proven to be good for the adsorption of Terbutaline as a priority pollutant in an aqueous solution, with pseudo-first order and Langmuir as the best-fitting models for the kinetic and isotherm models respectively.

Differences in fish assemblages’ structure and their relation with environmental variables (due to the variations in sampled seasons, habitats, and zones), were analyzed in two adjacent estuaries on the north Pacific coast of Mexico. Environmental variables and fish catches were registered monthly between August 2018 and October 2020. Multivariate analyses were conducted to define habitats and zones based on their environmental characteristics, and the effect of this variability on fish assemblages’ composition, biomass, and diversity (α and β) was evaluated. A total of 12,008 fish individuals of 143 species were collected using different fishing nets. Multivariate analyses indicated that fish assemblages’ structure was different between zones due to the presence, height, and coverage of distinct mangrove species. Additionally, factors such as depth and salinity showed effects on fish assemblages’ diversity (α and β-nestedness), which presented higher values in the ocean and remained similar in the rest of the analyzed zones and habitats. These results and the differences in species replacement (β-turnover) indicate the singularity of fish assemblages at estuaries (even in areas very close to the ocean), and the necessity to establish local management strategies for these ecosystems.

Approximately one-third of mankind is chronically exposed to the carcinogenic aflatoxin M1 contained in milk and dairy products and there is no ready to use procedure for decontamination purposes applicable in milk technology. Since β-cyclodextrin is frequently used in food industry, its effect on aflatoxin M1 concentration was investigated during cholesterol removal. So, milk samples were spiked with aflatoxin M1 at the average level 0.89 µg/kg and cholesterol removal was carried out by 2.0% (w/w) β-cyclodextrin addition. As found, average cholesterol concentration decreased by 92.3% while aflatoxin M1 concentration decreased to 0.53 µg/kg, i. e. by 39.1% after the treatment. The procedure itself is easy, inexpensive, and ready to use in milk processing technology on current production lines without any investments, thus fully applicable with a high potential of full aflatoxin M1 milk decontamination efficiency and such way to strengthen considerably the food safety issues associated with milk and dairy products on global level.

Diabetes mellitus (DM) is one of the most prevalent metabolic disorders. In order to replace the function of the destroyed pancreatic beta cells in diabetes, islet transplantation is the widely practiced treatment; however, it has several limitations. As an alternative approach, human pluripotent stem cells (hPSCs) can provide an unlimited source of pancreatic cells that have the ability to secrete insulin in response to high blood glucose level. However, determination of the appropriate pancreatic lineage candidate for the purpose of cell therapy for treatment of diabetes is still debated upon. While hPSC-derived beta cells are perceived as the ultimate candidate, the efficiency needs further improvement in order to obtain a sufficient number of glucose responsive β-cells for transplantation therapy. On the other hand, hPSC-derived pancreatic progenitors can be efficiently generated in vitro and can further mature into glucose responsive beta cells in vivo after transplantation. Herein, we discuss the advantages and predicted challenges associated with the use of each of the two pancreatic lineage products for diabetes cell therapy. Furthermore, we address co-generation of functionally relevant islet cell subpopulations and structural properties contributing to glucose responsiveness of beta cells, as well as the available encapsulation technology for these cells.

Substrate binding proteins (SBP) bind to specific ligands in the periplasmic region and bind to membrane proteins to participate in transport or signal transduction. Typical SBPs consist of two α/β domains and recognize the substrate by hinge motion between two domains. Conversely, short length Rhodothermus marinus SBP (named as RmSBP) exists around the methyl-accepting chemotaxis protein. We previously determined the crystal structure of RmSBP consisting of a single α/β domain, but the substrate recognition mechanism is still unclear. To better understand the short length RmSBP, we performed comparative structure analysis, computational substrate docking, and X-ray crystallographic study. RmSBP shares a high level of similarity in α/β domain with other SBP proteins, but it has a distinct topology in the C-term region. The substrate binding model suggested that conformational change in the peripheral region of RmSBP was required to recognize the substrate. We determined the crystal structures of RmSBP at pH 5.5, 6.0, and 7.5. RmSBP showed structural flexibility of the β1-α2 loop, β5-β6 loop, and extended C-term domain based on the electron density map and temperature B-factor analysis. These results provide information that will further the understanding of the function of the short length SBP.

Because of lower solubility and considerable metabolism, vardenafil (VRD) bioavailability is 15 %. To get over this obstacle, this study aimed to increase the solubility, hasten the onset of action, and mask the unpleasant taste of VRD utilizing β-cyclodextrin (β-CD) and formulation of the inclusion complex as oral disintegrating tablets (ODTs). The solubility of the obtained complexes in various ratios has been studied. A Box-Behnken design (BBD) was utilized to investigate the influence of excipients on the quality of ODTs. The solubility of VRD was improved at 1:2 drug: β-CD ratio. The formulated VRD-ODTs exhibited satisfying results regarding the hardness and disintegration time. In addition, in vivo taste masking and disintegration time showed improved results, after placing the tablets in the oral cavity of the healthy volunteers. The pharmacokinetic parameters for the optimized VRD–ODTs exhibited a significant improvement with P < 0.05 in the maximum plasma concentration and reduction in the time needed to reach this concentration when compared with the marketed tablets. Finally, the optimized VRD-ODTs exhibited increased oral absorption of VRD and subsequent decreasing the time of onset of clinical effect and masking the unpleasant taste, which is favored for patients with erectile dysfunction.

TGF-β signaling transduces immunosuppressive biochemical and mechanical signals in the tumor microenvironment. In addition to canonical SMAD signaling, TGF-β can promote tumor growth and survival by inhibiting proinflammatory signaling and extracellular matrix remodeling. In this article, we will review how TAK1 activation lies at the intersection of proinflammatory signaling by immune receptors and anti-inflammatory signaling by TGF-β receptors. Additionally, we will discuss the role of TGF-β in the mechanobiology of cancer. Understanding how TGF-β dampens proinflammatory responses and induces pro-survival mechanical signals throughout cancer development will be critical in designing therapeutics which inhibit tumor progression while bolstering the immune response.

Crosstalk between the BMP and TGF-β signaling pathways regulates many complex developmental processes from the earliest stages of embryogenesis throughout adult life. In many situations, the two signaling pathways act reciprocally. For example, TGF-β signaling is generally pro-fibrotic whereas BMP signaling is anti-fibrotic and pro-calcific. Sex-specific differences occur in many diseases including cardiovascular pathologies. Differing ratios of fibrosis and calcification in stenotic valves suggests that BMP/TGF-β signaling may vary in men and women. In this review, we focus on the current understanding of the interplay between sex and BMP/TGF-β signaling and pose several unanswered questions.

β-Lactams are pharmacologically important compounds because of their various biological uses, including antibiotic and so on. β-Lactams were synthesized from benzylidene-inden derivatives and acetoxyacetyl chloride. The inhibitory effect of these compounds was also examined for human carbonic anhydrase I and II (hCA I, and II) and acetylcholinesterase (AChE). The results reveal that β-lactams are inhibitors of hCA I, II and AChE. The K_i values of β-lactams (2a-k) were 0.44-6.29 nM against hCA I, 0.93-8.34 nM against hCA II, and 0.25-1.13 nM against AChE. Our findings indicate that β-lactams (2a-k) inhibit both CA isoenzymes and AChE at low nanomolar concentrations.

Weight loss solutions are on the rise, and there is growing interest in natural alternatives to the pharmaceuticals in the market, which are not devoid of relevant side effects. To this end, the objective of the current study is to assess the effects of a botanical-based blend comprised of lemon verbena and hibiscus extracts in weight management, body fat, appetite, lipid, and glucose profiles, in an overweight population, for 90 days. As a result, the volunteers presented significant weight loss in absence of diet, which coincided with decreased body fat. Body fat was assessed by anthropometry, electrical bioimpedance and DEXA scan. Cholesterol levels were also significantly decreased. Satiety assessment revealed that the product contributed to increased feeling of fullness and satisfaction after a meal, compared to the placebo group, which could contribute to the weight loss observed. Blood glucose and blood pressure levels remained unchanged, which was expected as the volunteers were normoglycemic and their blood pressure was in the healthy range. In conclusion, daily supplementation of a botanical-based blend contributes to weight loss in overweight individuals, in absence of diet, while not affecting other parameters that are in the healthy range. This product could be a candidate alternative or add-on to other weight loss products, as part of a healthy lifestyle.

Background: This study explored maternal gut, breast milk and infant gut microbiomes as possi-ble mediators of the observed effects of a relaxation intervention which reduced maternal stress and promoted infant weight gain. Methods: A randomized controlled trial was conducted in healthy Chinese primiparous mother-infant pairs. Mothers were randomly assigned to interven-tion group (IG, listening to relaxation meditation) or control group (CG). Outcomes were differ-ences in microbiome composition and diversity in maternal gut, breast milk and infant gut at 1- and 8-weeks between IG and CG, assessed by 16S rRNA gene amplicon sequencing of fecal and breastmilk samples. Results: 38 mother-infant pairs were included in this analysis (IG=19, CG=19). Overall microbiome community structure in the maternal gut was significantly different between IG and CG at 1-week and the difference was more significant at 8 weeks (Bray-Curtis distance R2=0.04 vs. R2=0.13). Post-intervention, the α-diversity was significantly lower in IG breast milk (observed features: CG=295 vs. IG=255, p=0.032); the Bifidobacterium genera presented higher relative abundance. In parallel, significantly higher α-diversity was observed in IG infant gut (observed features: CG=73 vs. IG=113, p

In this paper, a new full-Newton step feasible interior point method for convex quadratic programming is presented and analyzed. The idea behind this method is to replace the complementarity condition with a non-negative variable weight vector and use the algebraic equivalent transformation for the obtained equation. Under the selection of appropriate parameters, the quadratic rate of convergence of the new algorithm is established. In addition, the iteration complexity of the algorithm is obtained. Finally, some numerical results are presented to demonstrate the practical performance of the proposed algorithm.

Diabetes is one of the fatal diseases that play a vital role in the growth of other diseases in the human body. Controlling and curing diabetes in its early stages is the most significant technique to avoid its effects of diabetes. However, lack of awareness and expensive clinical tests are the primary reasons to skip clinical diagnosis and take preventive methods in lower-income countries like Bangladesh, Pakistan, and India. From this perspective, the study aims to build an automated machine learning (ML) model, which will predict diabetes at an early stage using socio-demographic characteristics rather than clinical attributes. Because clinical features are not always known to all people from lower-income countries. To find the best fit supervised ML classifier of the model, we applied six classification algorithms and found that RF outperformed with an accuracy of 99.36%. In addition, the most significant risk factors were found based on the SHAP value by all the applied classifiers. The study reveals that polyuria, polydipsia, and delayed healing are the most significant risk factors for growing diabetes. The findings indicate that the proposed model is highly capable of predicting diabetes in the early stages.

The gut microbiota plays an important role in the physiological activities of the host and affects the formation of important economic traits in agricultural animals. We investigated the effects of cecal microbiota on chicken weights using the Guizhou yellow chicken as a model. We collected experimental cohorts from chickens with high (HC, n=16) and low body weights (LC, n=16) and integrated microbial 16S rRNA gene sequencing and non-targeted serum metabolome data to explore the effect and its metabolic mechanism of cecal microbiota on market weight. The genera Lachnoclostridium, Alistipes, Negativibacillus, Sellimonas and Ruminococcus torques group were enriched in the HC group while Phascolarctobacterium was enriched in the LC group (P<0.05). Metabolomic analysis determined that pantothenic acid, luvangetin (2H-1-benzopyran-6-acrylic acid) and menadione (vitamin K) were significantly higher in HC serum while beclomethasone dipropionate (a glucocorticoid) and chlorophene (2-benzyl-4-chlorophenol) were present at higher levels in the LC group. The microbes enriched in HC that were significantly positively correlated with metabolites including pantothenic acid and menadione and negatively correlated with beclomethasone dipropionate and chlorophene. These results indicated that specific cecal bacteria in Guizhou yellow chickens alter the host metabolism and growth performance. This study provides a reference for revealing the mechanism of cecal microbe actions that affect chicken body weight.

Body weight support (BWS) and incline running (IR) are commonly used either during rehabilitation or during training separately, with many positive effects on athletes’ performance and rehabilitation. The aim of this study is to investigate the effect of BWS and IR. In eighteen healthy men (age: 20.3 ± 1.2 yr, body weight: 70.2 ± 4.8 kg, body height: 179.6 ± 5.4 cm), the changes in electromyographic activity (EMGA) during a 10-min run with BWS (15% or 30% of body weight; in different occasions) and IR at 7%, as well as jumping performance and gait spatiotemporal parameters were evaluated. Lower Rating of Perceived Exertion and a significant decrease in VL (33,4%), SOL (17%), and GL EMGA (28.5%, p &lt; 0.05) but not in GM (10.5%, p &gt; 0.05), were observed during BWS30% at 7% slope compared to flat running. Also, low-frequency fatigue of the quadriceps was induced only after running without BWS at 7% slope (P = 0.011). No changes were found in jumping performance (p = 0.246) and gait spatiotemporal parameters (p &gt; 0.05) except for flight time (p &lt; 0.006). In conclusion, compared to normal flat running, BWS reduces electromyographic activity and fatigue during slope running.

In the context of economic development and international economic integration, the logistics industry in Vietnam is developing to meet the market demand for the transportation of goods; thus, many logistics enterprises have been formulated and grown up in recent years. This research aims to measure the efficiency of logistics enterprises and recommend a feasible solution to improve their future performance by integrating the Super Slacked-based Measure model (Super-SBM) in Data Envelopment Analysis and Fuzzy Analytic Hierarchy Processes (Fuzzy AHP) in multi-criteria decision-making. The super-SBM model was utilized to conduct the efficiency scores of logistics enterprises from 2016 to 2022 based on calculating the ratio between input and output variables; the empirical result determined each enterprise's effectiveness and ineffectiveness. Next, the Fuzzy AHP method evaluated and ranked criteria that directly impacted the operational process of logistics enterprises based on experts' opinions; the examined result suggested a feasible direction to improve their business efficiency in the future. The proposed hybrid models are a helpful solution for efficiency determination and development direction for logistics enterprises. An overall picture of the logistics enterprises was also drawn to describe their operational business process.

Background: Changes in body weight are associated with the regulation of DNA methylation (DNAm). In this study, we investigated the associations between maternal gestational weight gain-related DNAm and foetal and neonatal body composition. Methods: Brazilian pregnant women from the Araraquara Cohort Study were followed up during pregnancy, delivery, and after hospital discharge. Women with normal pre-pregnancy BMI were allocated to two groups: adequate gestational weight gain (AGWG, n=45) and excessive gestational weight gain (EGWG, n=30). Foetal and neonatal body composition was evaluated by ultrasound and plethysmography, respectively. DNAm was assessed in maternal blood using Illumina Infinium MethylationEPIC BeadChip arrays. Linear regression models were used to explore the associations between DNAm and foetal and neonatal body composition. Results: Maternal weight, GWG, neonatal weight, and fat mass were higher in the EGWG group. Analysis of DNAm identified 46 differentially methyl-ated positions and 11 differentially methylated regions (DMRs) between the EGWG and AGWG groups. Nine human phenotypes were enriched for these 11 DMRs located in 13 genes (EMILIN1, HOXA5, CPT1B, CLDN9, ZFP57, BRCA1, POU5F1, ANKRD33, HLA-B, RANBP17, ZMYND11, DIP2C, TMEM232), highlighting the terms insulin resistance, and hyperglycaemia. Maternal DNAm was associated with foetal total thigh and arm tissues and subcutaneous thigh and arm fat, as well as with neonatal fat mass percentage and fat mass. Conclusion: The methylation pat-tern in the EGWG group indicated a risk for developing chronic diseases and involvement of ma-ternal DNAm in foetal lean and fat mass and in neonatal fat mass.

The pre-pregnancy BMI and the gestational weight gain are two important determinants of pregnancy outcomes. The aim of this study was to determine obstetric outcomes associated with insufficient gestational weight gain in women with a pre-pregnancy BMI &lt; 18.5 kg/m2. This study was based on observational routinely-collected data from a University Hospital Maternity. The participants were allocated to the group sufficient or insufficient gestational weight gain: ≥ 12.5 kg and &lt; 12.5 kg respectively. Primary outcomes were the adjusted birth weight in percentiles (%) and the proportion of SGA newborns. Secondary outcomes were obstetric and perinatal outcomes. A total of 135 participants with a median age of 28±8 years were included. The adjusted birth weight in percentiles was significantly lower in the insufficient gestational weight gain group (27.2±45.4 vs 42.6±48.8 %; P&lt;0.001). Moreover, the insufficient gestational weight gain is associated with a higher risk of SGA (28.1% vs 11.3%; P=0.017). Our study also showed increased risks of premature rupture of membranes, anaemia and intrauterine growth restriction in women with an insufficient weight gain. Future studies should explore the risk factors associated with insufficient weight gain, in order to develop specific care for underweight pregnant women.

Objective To Identify risk factors of perinatal complications amongst macrosomic babies in a reference hospital structure. Method We conducted a case-control institutional based study. Cases and controls of singleton livebirths were extracted from the maternity registry from January 2017 to December 2019 The case population consisted of mother and child macrosomic couples with perinatal complications. The control group consisted of couples without perinatal complications. Matching was done on age and sex. The main primary end point was the risk factors for complications. Data were analyzed using R, software version3.0 in adjusted and unadjusted analysis with p<0.05 threshold considered statistically significant. Results Out of 362 couples, we had 186 cases and 176 controls. Maternal age ≥30 years (p=0.024); non-screening for gestational diabetes (p=0.027); history of caesarean section (p=0.041); weight gain ≥16 kg (p<0.001); maternal HIV (p=0.047); birth weight ≥4500g (p=0.015) and birth height ≥ 52.7 ±1.7cm (p=0.026) were risk factors. Conclusion The delivery of a macrosomic baby remains problematic in this setting. The improvement of the maternal-fetal prognosis requires quality prenatal surveillance and management by a multidisciplinary perinatal team involving obstetricians, endocrinologist, and neonatal pediatricians.

To Identify risk factors of perinatal complications amongst macrosomic babies in a reference hospital structure.We conducted a case-control institutional based study. Cases and controls of singleton livebirths were extracted from the maternity registry from January 2017 to December 2019 The case population consisted of mother and child macrosomic couples with perinatal complications. The control group consisted of couples without perinatal complications. Matching was done on age and sex. The main primary end point was the risk factors for complications. Data were analyzed using R, software version3.0 in adjusted and unadjusted analysis with p<0.05 threshold considered statistically significant.Out of 362 couples, we had 186 cases and 176 controls. Maternal age ≥30 years (p=0.024); non-screening for gestational diabetes (p=0.027); history of caesarean section (p=0.041); weight gain ≥16 kg (p<0.001); maternal HIV (p=0.047); birth weight ≥4500g (p=0.015) and birth height ≥ 52.7 ±1.7cm (p=0.026) were risk factors. The delivery of a macrosomic baby remains problematic in this setting. The improvement of the maternal-fetal prognosis requires quality prenatal surveillance and management by a multidisciplinary perinatal team involving obstetricians, endocrinologists and neonatal pediatricians.

Abstract: A lower bed single row for pineapple cultivation could protect pineapple from soil erosion in rainy season and during drought, however, disease problem could arise due to water logging. Two experiments using a lower bed single row was done to understand the ability of gypsum providing soil calcium (Ca) available to pineapple plant, resistance to heart rot disease, and give better effect on crop growth and fruit quality of the pineapple in Ultisol soil. In the first trial, four level dosis of gypsum (0, 1.0, 1.5, 2.0 Mg ha-1) and dolomite 2 Mg ha-1 were applied by spreading and incorporated into the soil which have saturated with inoculums of Phytophthora nicotianae. In the second trial, gypsum treatments (0, 1.0, 1.5, 2.0, 2.5 Mg ha-1) were applied in the row between the single row beds as a basic fertilizer. The result showed that P. nicotianae attacked the pineapple plants in all treatments at 6 weeks after planting (WAP), and at 10 WAP, the mortality of dolomite treatment reached 63.8%, significantly different than that for gypsum treatments (3.3-14.3%). In the second experiment, gypsum increased plant weight significantly at 3 until 9 months after planting especially when it was applied 1.5-2.5 Mg ha-1. Fruit texture, total soluble solid (TSS), titratable acidity (TA) were not significant different among the treatment but all meet the standards for grades of canned pineapple. Result showed that soil applied gypsum before planting provides soil calcium and met the plant Ca requirement during a period of early and fast growth step and safe for heart rot disease.

TThe passion of bodybuilding athletes for a symmetric, lean, heavily muscled body leads them to carry out exhausting exercise programs and restrictive eating regimens, sometimes resulting in disordered eating behaviors. This study investigates potential exacerbators on the development of disordered eating in bodybuilding and strength athletes. The study involved 103 Cypriot bodybuilding athletes of both sexes, performing at three levels: professional, recreational and strength athletes. The Eating Attitude Test 26 (EAT-26) and The Three Factor Eating Question-naire (TFEQ-R21) were used to evaluate disordered eating and eating behaviors respectively. The current study was performed under the auspices of the Hellenic Center of Education & Treatment of Eating Disorders (KEADD). The degree of deviation between the perceived ideal body weight and the actual body weight was associated with increased risk of eating disorder. Athletes who desired a lower body weight recorded higher scores on EAT-26 overall, (p=0.001), and the subscales of dieting (p=0.01) and bulimia. (p=0.001). Cognitive restraint and emotional eating scales of TFEQ-R21 were more pronounced in the non-professional athletes. (p=0.01). The emotional eating score was higher in women. There is a need for appropriate sport-specific, gender-specific preventive intervention to deescalate the risk of eating disorder, in both profes-sional and non-professional bodybuilding athletes.

Introduction: In general, everyone believes that the smallest preterm infants should achieve normal intrauterine growth rates, but many thinks that this is not possible with current nutrition guidelines. There is resistance to giving enough nutrition for fear of "toxicity". The difference in weight Z-score between birth and a corrected gestational age (CGA) at discharge is assess in postnatal growth in our unit. Material and methods: An observational study was done between January 2018 and December 2020 where all cases that had ≤ 29 weeks of GA at birth and survived to 36 weeks corrected GA or that were discharged home. An aggressive nutrition protocol including parenteral as well as enteral nutrition was followed. Patients and their weight trajectory was plotted on the Fenton 2013 growth curve. The patients who had had a smaller WZP difference were also plotted. Results: A total of 32 cases were found. The median change in Z-score between birth and discharge of the whole group was -0.52 (IQR 0.53). Six of 32 (19%) had a more than one WZP, all of whom had severe pathologies. The median decline in Z score for this group with poor growth was 1.24 (IQR 0.22). There were 26 cases with a < 1 WZP (81%) and a median Z score fall of 0.39 (IQR 0.55). No important complications secondary to the ingested volumes or parenteral nutrition were reported. Conclusion: The group of cases with a > 1 WZP drop had severe pathologies. All the other cases had adequate growth parallel to normal weight growth charts and a few cases had some catch-up growth. The study showed that it is possible for many preterm infants to achieve normal intrauterine growth rates if they are given enough nutrition, but bigger multicenter studies are needed to confirm these findings.

The passion of bodybuilding athletes for a symmetric, lean, heavily muscled body leads them to carry out exhausting exercise programs and restrictive eating regimens, sometimes resulting in disordered eating behaviors. This study investigates potential exacerbators on the development of disordered eating in bodybuilding and strength athletes. The study involved 103 Cypriot bodybuilding athletes of both sexes, performing at three levels: professional, recreational and strength athletes. The Eating Attitude Test 26 (EAT-26) and The Three Factor Eating Questionnaire (TFEQ-R21) were used to evaluate disordered eating and eating behaviors respectively. The current study was performed under the auspices of the Hellenic Center of Education & Treatment of Eating Disorders (KEADD). The degree of deviation between the perceived ideal body weight and the actual body weight was associated with increased risk of eating disorder. Athletes who desired a lower body weight recorded higher scores on EAT-26 overall, and the subscales of dieting and bulimia. Cognitive restraint and emotional eating scales of TFEQ-R21 were more pronounced in the non-professional athletes. The emotional eating score was higher in women. There is a need for appropriate sport-specific, gender-specific preventive intervention to deescalate the risk of eating disorder, in both professional and non-professional bodybuilding athletes.

Recent evidence suggests that among behavioral-lifestyle factors, adherence to a healthy dietary pattern such as the Mediterranean Diet (MedDiet) is linked not only to better psychological health and mental positive status but also to increased subjective well-being (SWB). Nevertheless, this association has been unexplored among individuals with excessive weight. This study explored whether adherence to the MedDiet and the intake of healthy foods such as fruits and vegetables (FV) are associated with increased happiness and life satisfaction among Spanish adults with overweight or obesity when weight, body image, and body satisfaction are also considered. A convenience sample of adult individuals with excessive weight completed self-reports on the study variables, and weight and BMI were measured by bioimpedance. No evidence of a relationship with SWB indicators was obtained for MedDiet global indicators, probably due to the low adherence to a healthy diet by these individuals. In contrast, FV intake, as a powerful indicator of healthy eating, was associated with life satisfaction when BMI and body image dimensions were considered, among which body satisfaction also had a key role. Moreover, life satisfaction fully mediated the relationship between FV consumption and happiness. Our findings are expected to make a relevant contribution to knowledge on the positive correlates or protective factors for overall well-being in obesity, including dietary habits and body appreciation. Our results may inform obesity management actions focused on inclusive, positive aesthetic models and promoting a healthy lifestyle for happiness in obesity.

: This paper presents a couple of meal monitoring systems for senile dementia patients by using electronic weight and temperature sensors. These monitoring systems enable to convey the information of the amount of meal taken by the patients in real-time via wireless communication networks onto the mobile phones of their families or nurses in charge. Thereby, the nurses can easily spot the most desperate patient to take care of while the families can have relief to see the crucial information for survival of their parents at least three times a day. Meanwhile, the senile dementia patients tend to suffer the burn of their tongues because they can hardly recognize the temperature of hot meals served and therefore avoid the burn of tongues. This phenomenon can be discarded by utilizing the meal temperature monitoring system which displays alarm to the patients when the meal temperature is above the reference. These meal monitoring systems can be easily implemented by utilizing low-cost sensor chips and Arduino UNO boards so that elder-care hospitals and nursing homes can afford to exploit them with no additional cost. Hence, we believe that the proposed monitoring systems would be a potential solution to provide a great help and relief not only for the professional nursing nurses working in elder-care hospitals and nursing homes, but also for the families of the dementia patients.

The aim of this study was to investigate the effect of condensed tannin (CTs) with differing molecular weight on their capacity to modify the fatty acid profile in milk. Twenty multiparous crossbred lactating dairy goats were assigned in a randomized complete block design (RCBD), and were subjected to receive the dietary treatments as followings; T1: control (with no CTs supplementation), T2: supplemented with mangosteen peel in a concentrate as a source of low molecular weight CTs at level of 3.0 %DM of CTs equivalent, T3: supplemented with the same diet with T2 but added with polyethylene glycol (PEG, as tannin inactivator) as the control of T2, and T4: supplemented with quebracho CT extract (UNITAN ATO, Buenos Aires, Argentina; 75-77 % tannins) in a concentrate as a source of high molecular weight CTs at level of 3.0 %DM of CTs equivalent, and T5) supplemented with the same diet with T4 but added with PEG as the control of T4. No significant change was detected for feed intake and nutrient digestibility indicate that CTs at level of 3.0 %DM of diet did not showed the detrimental effect to feed intake and nutrient digestibility, however, ruminal fermentation parameters and milk yield and milk compositions did not affected by different source of CT inclusion.

With the rapid spread of carbon trading in the global economy, the interactions of prices between carbon (or clean/renewable energy) and traditional fossil energies such as coal and oil have raised growing attention, but little research have discussed their dynamic volatility spillover and time-varying correlation. The purpose of this study is to investigate these issues, for the weekly data of EUA futures, Biofuel and Brent oil prices from 25 October 2009 to 5 July 2020. We employ the VAR-GARCH model with the BEKK specification. Our results are summarized as follows. At first, we identified the sudden changes and the volatility persistence in the three markets, and also confirmed that the volatility of the markets has changed significantly over time. Secondly, we find that there are a weak volatility spillover effect among the three markets, while a strong spillover effect between the EUA and Brent oil markets. Lastly, in financial markets, the EUA can be used as a hedging portfolio for the Biofuel and Brent oil markets. These results can help investors to well compose their portfolios and manage their investment risks, and help potential pollutant emission sources to join in carbon market in a cost-effective way.

Dietary approach is essential to obesity control, but the effectiveness of changes in meal frequency (MF) as strategies for loss and maintenance of body mass remain unclear. This study aimed to evaluate the influence of MF on a hypocaloric diet on weight loss, active ghrelin levels and metabolic indicators of women with obesity. This is a randomized, parallel clinical trial, including forty women, randomized in two groups, both following a hypocaloric diet, according to MF (G1 – six meals/day; G2 – three meals/day). Dietary, laboratory, anthropometric and body composition indicators were assessed, as well as energy expenditure (EE), before and after the 90 days of intervention. After intervention, both groups decreased body weight, body mass index (BMI), waist circumference, fat mass (FM), insulin and HOMA-IR. G1 increased insulin sensitivity and G2 reduced triglyceride and FM and increased fat-free mass (FFM). MF increased ghrelin levels. There were no differences in EE variables. Hypocaloric diet with different MF promoted a reduction in total weight, BMI, WC and FM and an improvement in glycidic metabolism. However, the accomplishment of the three meals/day increased the FFM and active ghrelin and reduced triglyceride, while six meals/day was more beneficial in increasing insulin sensitivity.

We do fuzzification the concept of domination in crisp graph by using membership values of nodes, $\alpha$-strong arcs and arcs. In this paper, we introduce a new variation on the domination theme which we call vertex domination. We determine the vertex domination number $\gamma_v$ for several classes of fuzzy graphs, specially complete fuzzy graph and complete bipartite fuzzy graphs. The bounds is obtained for the vertex domination number of fuzzy graphs. Also the relationship between $M$-strong arcs and $\alpha$-strong is obtained. In fuzzy graphs, monotone decreasing property and monotone increasing property is introduced. We prove the vizing's conjecture is monotone decreasing fuzzy graph property for vertex domination. we prove also the Grarier-Khelladi's conjecture is monotone decreasing fuzzy graph property for it. We obtain Nordhaus-Gaddum (NG) type results for these parameters. The relationship between several classes of operations on fuzzy graphs with the vertex domination number of them is studied.

Fetal weight estimation before delivery is important in obstetrics, which assists doctors diagnose abnormal or diseased cases. Linear regression based on ultrasound measures such as bi-parietal diameter (bpd), head circumference (hc), abdominal circumference (ac), and fetal length (fl) is common statistical method for weight estimation but the regression model requires that time points of collecting such measures must not be too far from last ultrasound scans. Therefore this research proposes a method of early weight estimation based on expectation maximization (EM) algorithm so that ultrasound measures can be taken at any time points in gestational period. In other words, gestational sample can lack some or many fetus weights, which gives facilities to practitioners because practitioners need not concern fetus weights when taking ultrasound examinations. The proposed method is called dual regression expectation maximization (DREM) algorithm. Experimental results indicate that accuracy of DREM decreases insignificantly when completion of ultrasound sample decreases significantly. So it is proved that DREM withstands missing values in incomplete sample or sparse sample.

This review article focuses on the current state-of-the-art in the area of cellular and molecular biotechnology for over-production of clinically relevant therapeutic and anabolic growth factors. We discuss how the currently available tools and emerging technologies can be used for the regenerative treatment of osteoarthritis (OA). Transfected protein packaging cell lines such as GP-293 cells may be used as “cellular factories” for large-scale production of therapeutic proteins and pro-anabolic growth factors, particularly in the context of cartilage regeneration. However, when irradiated with gamma or x-rays, these cells lose their capacity for replication, which actually makes them safe for use as a live cell component of intra-articular injections. This innovation is already here, in the form of TissueGene-C, a new biological drug which consists of normal allogeneic primary chondrocytes combined with transduced GP2-293 cells that overexpress the growth factor transforming growth factor β1 (TGF-β1). TissueGene-C has revolutionized the concept of cell therapy, allowing drug companies to develop live cells as biological drug delivery systems for direct intra-articular injection of growth factors whose half-lives are in the order of minutes. Therefore, in this paper, we discuss the potential for new innovations in regenerative medicine for degenerative diseases of synovial joints using mammalian protein production platforms, specifically protein packaging cell lines, for over-producing growth factors for cartilage tissue regeneration and give recent examples. Mammalian protein production platforms that incorporate protein packaging eukaryotic cell lines are superior to prokaryotic bacterial expression systems and are likely to have a significant impact on the development of new humanized biological growth factor therapies for treating focal cartilage defects and more generally for the treatment of degenerative joint diseases such as OA, especially when injected directly into the joint.

Growth factors, chemokines and cytokines guide tissue regeneration after injuries. However, their applications as recombinant proteins are almost non-existent due to the difficulty of maintaining their bioactivity in the protease-rich milieu of injured tissues in humans. Safety concerns have ruled out their systemic administration. The vascular system provides a natural platform for circumvent the limitations of the local delivery of protein-based therapeutics. Tissue selectivity in drug accumulation can be obtained as organ-specific molecular signatures exist in the blood vessels in each tissue, essentially forming a postal code system (“vascular zip codes”) within the vasculature. These target-specific “vascular zip codes” can be exploited in regenerative medicine as the angiogenic vasculature forming in the regenerating tissues has a unique molecular signature. The identification of vascular homing peptides capable of finding these unique “vascular zip codes” after their systemic administration provides an opportunity for the target-specific delivery of therapeutics to tissue injuries. Therapeutic proteins can be “packaged” together with homing peptides by expressing them as multi-functional recombinant proteins. These multi-functional recombinant proteins provide an example how molecular engineering gives a compound an ability to home to regenerating tissue and enhance its therapeutic potential. Regenerative medicine has been dominated by the locally applied therapeutic approaches despite these therapies are not moving to clinical medicine with success. There might be a time to change the paradigm towards systemically administered, target organ-specific therapeutic molecules in future drug discovery and development for regenerative medicine

Maternal unbalanced diets cause adverse metabolic programming and affect the offspring's liver microRNA profile. The liver is a site of β-carotene (BC) metabolism and a target of BC action. We studied the interaction of maternal Western diet (WD) and early-life BC supplementation on the epigenetic remodeling of offspring’s liver microRNAs. Mouse offspring of WD-fed mothers were given daily a placebo (controls) or BC during suckling. The liver miRNAome was analyzed in recently weaned animals by microarray hybridization. BC impacted the liver miRNAome differently in male and female offspring, with no overlap in differentially expressed (DE) miRNAs between sexes and more impact in females. Bioinformatic analysis of DE miRNA predicted target genes revealed enrichment in biological processes/pathways related to metabolic processes, regulation of developmental growth and circadian rhythm, liver homeostasis and metabolism, insulin resistance, and neurodegeneration, among others, with differences between sexes. Fifty five percent of the overlapping target genes in both sexes identified were targeted by DE miRNAs changed in opposite directions in males and females. The results identify sex-dependent responses of the liver miRNA expression profile to BC supplementation during suckling and may sustain further investigations regarding the long-term impact of early postnatal life BC supplementation on top of an unbalanced maternal diet.

Sporadic Alzheimer’s disease (AD) derives from an interplay among environmental factors and genetic variants, while epigenetic modifications have been expected to affect the onset and progression of its complex etiopathology. Heterozygous carriers of the apolipoprotein E gene (APOE)4 allele have a 4-fold increased risk of developing AD, while APOE 4/4-carriers have a 12-fold increased risk in comparison with the APOE 3-carriers. The main longevity factor is the homozygous APOE ε3/ε3 genotype. In the present narrative review article, we summarized and described the role of APOE epigenetics in aging and AD pathophysiology. It is not fully understood how APOE variants may increase or decrease AD risk, but this gene is known to affect amyloid- and tau-mediated neurodegeneration directly or indirectly, also by affecting lipid metabolism and inflammation. For sporadic AD, epigenetic regulatory mechanisms may control and influence APOE expression in response to external insults. Diet, a major environmental factor, has been significant associated with physical exercise, cognitive function, and the methylation level of several cytosine-phosphate-guanine (CpG) dinucleotides sites of APOE.

Breast cancer (BC) is the most common malignancy and the second cause of cancer specific death in women from high-income countries. More than 70% of all breast cancer are hormone receptor-positive BC, and elevated estrogen circulating in blood has been proved to be a strong risk for BC development. This is due to its contribution to enhance proliferation of cancerous cells, angiogenesis and metastasis stimulation and therapy resistance. The estrogen (E) metabolism–gut microbiome axis is functional with underlying individual variations in E levels. It is reasonable that the estrobolome (bacterial genes whose products are capable of metabolizing E) could contribute to the risk of hormone-driven malignancies including BC and may serve as a potential biomarker and target. Gut microbial β -glucuronidase (GUS) enzymes have been suggested to be involved in the estrobolome. Furthermore, bacterial GUS enzymes within the gastrointestinal tract have been postulated to contribute to hormone breast cancer. In this review, we discuss the recent knowledge about the role of GUS enzyme in the pathogenesis of breast cancer. We focus on the role of GUS in (i)-the microbioma and estrogen metabolism, (ii) diet, estrobolome, and the BC development, (iii) other activities of the bacterial β-glucuronidase, and (iv) the new molecular target for BC therapeutic application.

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease due to early metastatic spread, late diagnosis and the lack of efficient therapies. A major driver of cancer progression and hurdle to successful treatment is transforming growth factor (TGF)-β. Recent data from pancreatic cancer mouse models have shown that transcriptionally active p73 (TAp73), a p53 family member, inhibits tumor progression through promoting tumor suppressive canonical TGF-β/Smad signaling, while preventing non-canonical TGF-β signaling through extracellular signal-regulated kinases (ERK)1/2. Here, we have studied whether this mechanism also operates in human PDAC. Using the PDAC-derived tumor cell lines PANC-1 and HPAFII, we show that TAp73 induces the expression of the epithelial marker and invasion suppressor E-cadherin and the common-mediator Smad, SMAD4, while at the same time suppressing expression of the EMT master regulator SNAIL and basal and TGF-β1-induced activation of ERK1 and ERK2. Using dominant-negative and RNA interference-based inhibition of SMAD4 function we went on to show that inhibition of ERK activation by TAp73 is mediated through SMAD4. Intriguingly, both SMAD4 and the α isoform of TAp73 - but not the isoform - interfered with cell migration as shown by xCELLigence technology. Our findings highlight the role of TAp73-SMAD4 signaling in tumor suppression of human PDAC and identify direct inhibition of basal and TGF-β-stimulated pro-invasive ERK activation as an underlying mechanism.

Alzheimer’s disease (AD) is characterized by the formation of senile plaques consisting fibrillated amyloid-β (Aβ), dystrophic neurites, and the neurofibrillary tangles of tau. The oligomers/fibrillar Aβ damages the neurons or initiate an intracellular signaling cascade for neuronal cell death leading to Aβ toxicity. The Aβ is a 4 kDa molecular weight peptide originating from the C-terminal region of the amyloid precursor protein via proteolytic cleavage. Apart from the typical AD hallmarks, certain deficits in metabolic alterations have been identified. This study describes the emerging features of AD from the aspect of alternation in the main pathway of carbohydrate metabolism in the human brain. Particularly, the neurons in patients with AD favor glycolysis despite a normal mitochondrial function indicating a Warburg-like effect. In addition, certain dietary patterns are well known for their properties in preventing AD. Among those, a ketogenic diet may substantially improve the symptoms of AD. An effective therapeutic method in the treatment, mitigation, and prevention of AD has not yet been established. Therefore, the researchers pursue the development and establishment of novel therapies effective in suppressing AD symptoms and the elucidation of their underlying protective mechanisms against neurodegeneration aiming for AD therapy in near future.

Cannabis Sativa L. has been used for a long time to obtain food, fiber and as a medicinal and psychoactive plant. Today the nutraceutical potential of C. Sativa is being increasingly reappraised; however, C. Sativa roots remain poorly studied, despite citations in the scientific literature. In this direction, we identified and quantified the presence of valuable bioactives (namely β-sitosterol, stigmasterol, campesterol, friedelin and epi-friedelanol) in the root extracts of C. Sativa, a finding which might pave the way to the exploitation of the therapeutic potential of C. Sativa in all its parts. To facilitate roots harvesting and processing, aeroponic (AP) and aeroponic elicited cultures (AEP), have been set up and compared to soil-cultivated plant (SP): interestingly a considerable overgrowth of the plants - particularly of roots - and a significant increase (up to 20 fold in the case of β-sitosterol) in the total content of the above roots’ bioactive molecules have been observed in AP and AEP. In conclusion aeroponics, an easy, standardised, free of contaminant cultivation tecchnique, allows an ease harvesting/processing of roots along with a greater production of their secondary bioactive metabolites which could be utilized in the formulation of health promoting and health care products.

The influence of the hot isostatic pressing (HIP) post-processing step on structural and phase changes, porosity healing and mechanical strength in a powder metallurgy Ti35Nb2Sn alloy was studied. Powders were pressed at room temperature at 750 MPa, and then sintered at 1,350°C in a vacuum for 3 h. The standard HIP process at 1,200°C and 150 MPa for 3 h was performed to study its effect on a Ti35Nb2Sn powder metallurgy alloy. The influence of the HIP process and cold rate on density, microstructure, the quantity of interstitial elements, mechanical strength and Young's modulus was investigated. HIP post-processing for 2 h at 1,200°C and 150 MPa led to greater porosity reduction and a marked retention of the β phase at room temperature. The slow cooling rate during the HIP process affected phase stability, with a large amount of α”-phase precipitate, which decreased the titanium alloy’s yield strength.

Cereal crops, such as oats and barley, possess a number of valuable properties that meet the requirements for functional diet components. This review summarized the available information about bioactive compounds of oat and barley grain. The results of studying the structure and physicochemical properties of the cell wall polysaccharides of barley and oat are presented. The main components of the flavonoids formation pathway are shown and data, concerning anthocyanins biosynthesis in various barley tissues, are discussed. Moreover, we analyzed the available information about structural and regulatory genes of anthocyanin biosynthesis in Hordeum vulgare L. genome, including β-glucan biosynthesis genes in Avena sativa L species. However, there is not enough knowledge about genes responsible for biosynthesis of β-glucans and corresponding enzymes and plant polyphenols. The review also covers contemporary studies about collections of oat and barley genetic resources held by VIR. This review intended to provide information on the processes of biosynthesis of biologically active compounds in cereals that will promote further researches devoted to transcription factors controlling expression of structural genes and their role in other physiological processes in higher plants. Found achievements will allow breeders to create new highly productive varieties with the desirable properties.

Autophagy refers to the degradation of cytoplasmic constituents by a lysosomal-mediated pathway, which plays a critical role in maintaining cellular homeostasis. Importantly, dysregulation of autophagy has been implicated in multiple neurodegenerative disorders. Previous studies reported that autophagy affects the processing of amyloid precursor protein (APP), thus stimulating β‐amyloid (Aβ) production in Alzheimer’s disease (AD) eventually. Although the mechanism of autophagy modulation on APP processing and its pathogenesis has not yet been fully elucidated at the molecular level, but modulation of autophagy has received considerable attention as a promising approach for the treatment of AD. In the early stage of AD, Aβ may prompt autophagy to facilitate its removal via mTOR‐independent as well as-dependent pathways. However, a recent study proposed that autophagy processes are not properly regulated as AD continues to progress, and consequently, the production of Aβ tends to accumulate rapidly. Meanwhile, a number of autophagy-related genes (Atg) as well as APP genes are also thought to influence the development of AD, which may serve as a bi‐directional link to autophagy and AD pathology. In this review, we summarized current observations related to autophagy regulation and APP processing, focusing on their dynamic modifications associated with the progression of AD. Recent findings together highlight the essential role of autophagy in the removal and clearance of APP and Aβ deposition in the pathological condition of AD.

Thymic stromal lymphopoietin (TSLP) is a cytokine and is closely related to Interleukin (IL) - 7, and hTSLP can activation through the human thymus dendritic cell in thymic to indirectly promote the differentiation of natural Regulatory T cells (Tregs) of the thymus. In this study, we focused on recombinant TSLP to determine its effects on the differentiation of CD4+CD25-T cells separated from the thymus of myasthenia gravis (MG) patients. Our results demonstrated that exogenous TSLP could increase CD4+CD25+T/CD4+T cells ratio, up-regulate the expression of Foxp3 mRNA and protein expression in CD4+CD25+Treg cells. Furthermore, we found that CD4+CD25+ Treg cells induced by exogenous TSLP could secrete IL - 10, Transforming growth factor (TGF) - β and the ability to inhibit CD4+T cell proliferation improved. These results indicate that TSLP may promote the differentiation of thymic CD4+CD25-T cells of MG patient to CD4+CD25+Foxp3+ regulatory T cells and enhance the function of immune suppression.

Innovations in drug delivery systems are crucial for enhancing therapeutic efficiency. Our research presents a novel approach based on Electro-fluid dynamic atomization (EFDA) to fabricate core-shell monophasic particles (CSMp) from sodium alginate blends of varying molecular weights. This study explores the morphological characteristics of these particles in relation to material properties and process conditions, highlighting their potential in drug delivery applications. A key aspect of our work is the development of a mathematical model that simulates the release kinetics of small molecules, specifically sodium diclofenac. By assessing the diffusion properties of different molecules and gel formulations through transport and rheological models, we have created a predictive tool for evaluating the efficiency of these particles in drug delivery. Our findings underscore two critical independent parameters for optimizing drug release: the external shell thickness and the diffusivity ratios within the dual layers. This allows for precise control over the timing and intensity of the release profile. The study advances our understanding of EFDA in the fabrication of CSMp and offers promising avenues for enhancing drug delivery systems by tailoring release profiles through particle characteristic manipulation.

The study examines the return performance and resilience to market volatility of the recently introduced Environment, Social/Sustainable, and Governance (ESG) weight-tilted Hang Seng Index (HSIESG) compared to its parent, the Hang Seng Index (HSI). The ESG-infused index has a higher mean return and lower return volatility than the parent index, although the differences are statistically and economically insignificant, a result consistent with the high correlation between the two index returns. Most important, the ESG weighted-tilted index is more resilient to volatility spikes than the parent index and therefore has lower downside risks. The overall results show that stocks with high ESG ratings are less susceptible to trading pressures triggered by volatility-induced turnovers. The paper contributes to the literature by providing significant incremental information on the emerging market for ESG-related equity products in Hong Kong.

Chicken collagen is a promising raw material source to produce gelatins and hydrolysates. Gelatins and hydrolysates can be prepared biotechnologically using proteolytic enzymes produced by submerged fermentation of genetically modified microorganisms. By choosing the appropriate process conditions, such changes can be achieved at the molecular level of collagen, making it possible to prepare products with targeted properties for advanced cosmetic, pharmaceutical, medical or food applications. The research aims to investigate: i) antioxidant activity (DPPH and ABTS) in model samples of chicken collagen products (gelatin and hydrolysates); ii) distribution of molecular weights by the GPC-RID analysis method; iii) functional groups and configuration of polypeptide chains related to molecular level properties using FTIR; iv) the microbiological properties on SDA, PCA, TSA and VRBL microbial populations using MALDI method. Antioxidant activity towards ABTS radicals of more than 80% was found for all samples. The molecular weights of all gelatin samples showed typical α- and β-chains. FTIR analysis confirmed that the samples showed all typical vibrational regions for collagen cleavage products, Amide A and B, Amide I, II, and III at characteristic values. Microbiological analysis of the prepared samples showed no undesirable bacteria that would limit advanced applications of the prepared products. Gelatins and hydrolysates from chicken stomachs represent a promising alternative to products made from standard collagen tissues of terrestrial animals.

Effects and interactions of incubation time and chick preplacement holding time on mortality at placement, utilization of yolk sac, crop filling rate, early feeding–drinking behavior and broiler live performance were investigated. Ross 308 broiler hatching eggs from a 39-week-old flock were set in two identical setters in a commercial hatchery,with setting time 12 hours earlier in one machine. At the end of incubation, chicks were removed from the hatchers at the same time. Thus, incubation times were either 504 h (normal incubation time (NIT) treatment) or 516 h (longer incubation time (LIT) treatment). After pull time, chicks from each incubation time group were subjected to either 6, 24, 48, 60 or 72 h preplacement holding times. At placement, chicks were given access to feed and water. In total, 19,200 chicks were randomly assigned to a total of 10 subtreatment groups (2 incubation times × 5 preplacement holding times). Therefore, a total of 1,920 chicks were used in each subtreatment group for the grow-out period in a commercial broiler house. An interaction was found between incubation time and preplacement holding time for residual yolk sac (RYS) weight (g, %) (p &lt; 0.001). RYS weight was greater at pull time and at 6 and 24 h of preplacement holding time in the NIT treatment compared to the LIT treatment, while differences were no longer evident at 48–72 h. The lowest percentage of chicks with full crops and eating activity was observed in the shortest preplacement holding time (6 h) group at 3 h after placement. As expected, the initial BW at placement clearly decreased with increasing duration after the pull time (p &lt; 0.05) with the highest and lowest weights were found in the 6 and 72 h holding time treatments respectively. This BW difference was still evident at 35 d after placement and chicks held for the longest period after the pull time (72 h) showed the lowest BW (p &lt; 0.001). However, there was no significant difference between the 6 and 60 h preplacement holding times. Mortality during the first 7 d after placement increased only when the preplacement holding time was extended to 72 h (p = 0.031). Similar to the 7 d results, chicks held for 72 h exhibited higher 0-35 day mortality compared to those held for 6 or 24 h (p = 0.028). Neither BW nor mortality was affected by incubation time treatment at 35 d after placement (p &gt; 0.05). It can be concluded that there were no significant differences in average BW and mortality, up to and including a 60-h holding time under thermal comfort conditions, but a 72-h preplacement holding time resulted in final BW and mortality being negatively affected. In addition, LIT tended to have a beneficial effect on BW and mortality compared to NIT when the preplacement holding time was shorter (6–24 h) but had a negative effect for extended holding times (48–72 h).

Wheat yield plays an important role in the global economy. Changing climate conditions and increased drought negatively affect grain yield. Currently, breeding programs are aimed at improving wheat productivity. To accelerate the selection process of hybrids and parental forms for crosses, it is essential to pay attention to plants' phenotypic and genetic potential. We studied the genes of the "green revolution" group Rht and coarse-grained TaGW and TaGS to increase yields by selecting optimal parameters for wheat. We focused on short-stemmed and coarse-grained characteristics in a dry climate and conducted a correlation analysis between the genetic potential of wheat varieties and hybrids and their phenotypic manifestation in drought conditions. Rht-D1b significantly reduced the height of plants by 51.67% and reduced the coleoptile length by 30.45%. At the same time, TaGW8-B1a increased the grain width by 13.37%. However, in the presence of Rht-D1b and Rht-B1b in the genome, the 1000-kernal weight was 35.06 g (p<0.05), the Rht-B1b gene enhanced it by 9% (p<0.05), while both Rht-D1a and Rht-B1a alleles gave a 1000-kernal weight of 37.96 g (p<0.05). The Rht-D1b and Rht-B1b alleles gave 18.5 seeds per ear, while the Rht-D1a and Rht-B1a alleles gave the value of grains per ear -24.1 pcs. The data obtained indicated the relationship of phenotypic and genetic parameters in wheat between the coarse-grained and short-stemmed genes, which makes it possible to select based on the genetic parameters of varieties and hybrids, thereby speeding up the selection process.

This work presents patient radiation dose data for pediatric interventional cardiology procedures in a large hospital in Colombia. The data collection period was from April 2020 to July 2022. The local DRLs were calculated as the 3rd quartile of patient dose data distributions for kerma area-product (Pka) values. The sample of collected clinical procedures (255) was divided into diagnostic and therapeutic procedures and grouped into five weight and five age bands. The Pka differences found between diagnostic and therapeutic procedures were statistically in all weight and age bands, except the group between 1-5 years. The local DRLs were 69 Gy/cm2 (< 5 kg), 3.44 Gy/cm2 (5-<15 kg), 8.87 Gy/cm2 (15-<30 kg), 10.51 Gy/cm2 (30-<50 kg) y 22.61 Gy/cm2 (50-<80 kg), respectively. In conclusion, from comparing our results with other existing DRL values, we are similar to other centers and scope to continue optimizing the radiation dose values. This will contribute to setting national diagnostic reference levels (DRLs) for Colombia in the near future.

In this paper, a Markov random field model is proposed to determine a site’s light pollution risk level. The specific data of 12 indicators of five typical cities in China is first collected to establish a hierarchical indicator system using an R-type clustering algorithm. Then, the entropy weight method is used to filter, determine 10-factor indicators, three potential impact indicators, and a light pollution risk index, and establish an undirected probability map model. A light pollution measurement based on Markov random field is obtained, and a location-based light pollution risk assessment index (LBLPRAI) is proposed. LBLPRAI of different types of sites is analyzed, and three possible intervention strategies are proposed to solve the light pollution problem: road lighting system planning, increasing vegetation coverage, and building system planning. Finally, the simulated annealing algorithm is used to determine the best intervention strategy, and it is concluded that the use of strategy 1 in the urban community 2 is the most effective measure, which can reduce the risk level of light pollution by 17.2%.

The present study was conducted the status of sea bass from Kokko and Kyuntone of The Gulf of Motttama Wetland (GoMW) area in Thanatpin Township in Bago Region Myanmar from September 2019 to August 2020. Fifty specimens were monthly collected, measured and weighed. Invoices of sea bass were collected for the depot and fish sellers by monthly. In Kokko, mean value of standard length and body weight were highest in March (32.70±1.58, 660.7±112.23). The mean value of standard length was peak in January (31.39±7.16) but peak of body weight was in March (963.24±280.86) in Kyuntone villages. The lowest mean value of standard length and body weight were found in June at both study areas. According to the invoice data revealed that monthly catch weight of sea bass is most abundance in October (829.92) kg in Kokko, (339.12) kg in Kyuntone. Based on price of relations to size group, small size C &lt; 300g (41%) was mostly abundance in Kokko and in Kyuntone small size C &lt; 300g (35%) was second abundance. Specimens were not landed in April and May. In June, young specimens were very rarely seen in both study sites. The important roles of wetland fishes, the economic valuation of GOMW in Myanmar and samples of fishing gear and value chain of sea bass in Myanmar was expressed in this study.

High temperature (HT) significantly affects the crop physiological traits and reduces the 12 productivity in plants. To increase yields as well as survival of crops under HT, developing heat13 tolerant plants is one of the main targets in crop breeding programs. The present study attempted 14 to investigate the linkage of the heat tolerance between the seedling and the reproductive growth 15 stages of tomato cultivars ’Dafnis‘ and ’Minichal’. This research was undertaken to evaluate heat 16 tolerance under two experimental designs such as screening at seedling stage and screening from 17 reproductive traits in greenhouses. Survival rate and physiological responses in seedlings of 18 tomatoes with 4-5 true leaf were estimated under HT (40 °C, RH 70%, day/night, respectively) and 19 under two control and HT greenhouse conditions (day time 28 °C and 40 °C, respectively). Heat 20 stress significantly affected physiological-chemical (photosynthesis, electrolyte conductivity, 21 proline) and vegetative parameters (plant height, shoot fresh weight, root fresh weight) in all 22 tomatoes seedlings. The finding revealed that regardless of tomato cultivars the photosynthesis, 23 chlorophyll, total proline and electrical conductivity parameters were varied in seedlings during the 24 heat stress period. The heat tolerance rate of tomatoes in the seedling stage might not be associated 25 always with reproductive parameters. HT reduced the fruit parameters likeas fruit weight (31.9%), 26 fruit length (14.1%), fruit diameter (19.1%) and fruit hardness (9.1%) in compared to NT under HT 27 in heat susceptible tomato cultivar ‘Dafnis’, while in heat tolerant cultivar ‘Minichal’ fruit length 28 (7.1%) and fruit diameter (12.1%) was decreased by the affect of HT but on the contrary fruit weight 29 (3.6%) and fruit hardness (8.3%) were increased. In conclusion, screening and selection for tomatoes 30 should be evaluated at the vegetative and reproductive stages with consideration of reproductive 31 parameters.

The synthesis of additives for thinning mineral suspensions based on sodium polyacrylate was carried out. The effect of molecular weight regulators on the molecular weight characteristics of the polymer and the effect of such polymers on the rheological properties of suspensions was studied. Sodium acrylate polymers are synthesized by free radical polymerization in aqueous solution using molecular weight regulators. The molecular weight characteristics of the polymeric samples were estimated by viscometry using Mark-Houwink-Kuhn-Sakurada (MHKS) equation. Synthesized polymers were used as thinners ceramic slurries, prepared according to the recipe of the enterprises producing ceramic products. The thinning ability of polymer samples with different molecular weights was estimated using an Engler viscometer from the time of the ceramic slurry flow. The influence of the type and amount molecular weight regulator on polyacryates was revealed. It was found that molecular weight synthesized samples was in the range of 21000 - 91000. It was determined that samples with a molecular weight of 28000 - 35000 synthesized using mercaptoethanol (at a dosage of 0.5-1.5% by weight of the monomer) provide optimal fluidity to the ceramic slurry.

.With the increasing use of carbon fiber reinforced plastics in various area, carbon fiber composites based on prepregs have attracted attention in industries and academia research. However, prepreg manufacturing processes are costly, and the strength of structures varies depending on the orientation and defects (pores and delamination). For non-contact evaluation of internal defects, we proposed lock-in infrared thermography to investigate orientation angles after a compression test. We also conducted a drop-weight impact test to study the behaviour of the composites after impact according the fibers orientation for composite fabricated using unidirectional carbon fiber prepregs. Using CAI tests, we determined the residual compressive strength and confirmed the damage modes using a thermal camera. The results of the drop weight impact tests show that the specimen laminated at 0° suffered the largest damage because of susceptibility of the resin to impact. In contrast, the specimens oriented in of 0°/90° and +45°/–45° directions transferred more than 90% of the impact energy back to the impactor because of the lamination of fibers in the orthogonal directions. Furthermore, the specimens that underwent complete damage in the impact tests were subjected to the lock-in method and showed internal delamination and cut fibers. With the finite elements analysis, the damage of each ply could be observed. Moreover, the temperature differences in the residual compression tests were not significant.

There is accumulating evidence that prenatal exposure to air pollution disturbs fetal growth and development, but little is known about these effects in cold climates or their season-specific or joint effects. Our objective was to assess independent and joint effects of prenatal exposure to specific air pollutants on the risk of low birth weight (LBW). We utilized the 2568 children of the Espoo Cohort Study, born between 1984 and 1990, and living in the City of Espoo. We conducted stratified analyses for births during warm and cold seasons separately. We analyzed the effect estimates using multi-pollutant Poisson regression models with risk ratio (RR) as the measure of effect. The risk of LBW was related to exposure to CO and (adjusted RR 1.44, 95% CI: 1.04-2.00) and exposure to O3 in the spring-summer season (1.82, 1.11-2.96). There was also evidence of synergistic effects between CO and O3 (relative risk due to interaction, RERI, all year 1.08, 95% CI: 0.27-4.94, spring-summer 3.97, 2.17-25.85) and PM2.5 and O3 (all year 0.72, -0.07-3.60, spring-summer 2.80, 1.36-19.88). We present new evidence of both independent and joint effects of prenatal exposure in a cold climate on the risk of LBW at low levels of air pollution.

By combing continuum topology optimization (TO) method and lattice structure technique, a sandwich aircraft spoiler with a high stiffness-to-weight is designed. TO method is served to produce the shell of the aircraft spoiler and the lattice structure, used as cores, is employed to support the shell. TO problem is established as maximizing the stiffness of the structure with limited material volume. Density-based method is utilized to achieve a 0/1 solution. We then empirically replace the core of the aircraft spoiler by using 3D kagome lattice structure. Two different materials, i.e., aluminum alloy and titanium alloy, are synthetically applied to further reduce the weight and simultaneously improve the strength of the aircraft spoiler. Numerical simulations are conducted to show that the designed aircraft spoiler can meet the service environment with a reduction of its weight by approximately 80% when compared with that of the initial design model. Finally, we have fabricated the designed model with photosensitive resin by using 3D printing technique.

The domestication and subsequent genetic improvement of wheat led to the development of large-seeded cultivated wheat species relative to their smaller-seeded wild progenitors. While increased grain weight (GW) continues to be an important goal of many wheat breeding programs, few genes underlying this trait have been identified despite an abundance of studies reporting quantitative trait loci (QTLs) for GW. Here we perform a QTL analysis for GW using a population of recombinant inbred lines (RILs) derived from the cross between wild emmer wheat accession ‘Zavitan’ and durum wheat variety ‘Svevo’. Identified QTLs in this population were anchored to the recent Zavitan reference genome, along with previously published QTLs for GW in tetraploid wheat. This genome-based, meta-QTL analysis enabled the identification of a locus on chromosome 6A whose introgression from wild wheat positively affects GW. The locus was validated using an introgression line carrying the 6A GW QTL region from Zavitan in a Svevo background, resulting in >8% increase in GW compared to Svevo. Using the reference sequence for the 6A QTL region, we identified a wheat ortholog to OsGRF4, a rice gene previously associated with GW. The coding sequence of this gene (TtGRF4-A) contains four SNPs between Zavitan and Svevo, one of which reveals the Zavitan allele to be rare in a core collection of wild emmer and completely absent from the domesticated emmer genepool. Similarly, another wild emmer accession (G18-16) was found to carry a rare allele of TtGRF4-A that also positively affects GW and is characterized by a unique SNP absent from the entire core collection. These results exemplify the rich genetic diversity of wild wheat, posit TtGRF4-A as a candidate gene underlying the 6A GW QTL, and suggest that the natural Zavitan and G18-16 alleles of TtGRF4-A have potential to increase wheat yields in breeding programs.

In this paper we show that the Schwarzschild radius can be extracted easily from any gravitationally-linked phenomena without having knowledge of the Newton gravitational constant or the mass size of the gravitational object. Further, the Schwarzschild radius can be used to predict any gravity phenomena accurately, again without knowledge of the Newton gravitational constant and also without knowledge of the size of the mass, although this may seem surprising at first. Hidden within the Schwarzschild radius are the mass of the gravitational object, the Planck mass (their relative mass), and the Planck length. We do not claim to have all the answers, but this seems to indicate that gravity is quantized, even at a cosmological scale, and this quantization is directly linked to the Planck units. This also supports our view that the Newton gravitational constant is a universal composite constant of the form $G=\frac{l_p^2{c}^3}{\hslash }$ , rather than relying on the Planck units as a function of G. This does not mean that Newton’s gravitational constant is not a universal constant, but that it is instead a composite universal constant that depends on the Planck length, the speed of light, and the Planck constant. Further, $\frac{G\times 1\hspace{0.17em}\mathrm{weight}\hspace{0.17em}\mathrm{unit}}{c^2}=\frac{G}{c^2}$ is the Schwarzschild radius off one weight unit. So G is only needed when we want to use gravity to find the weight of an object, such as weighing the Earth. This is, to our knowledge, the first paper that shows how a long series of major gravity predictions and measurements can be completed without any knowledge of the mass size of the object, or Newton’s gravitational constant. As a minimum we think it provides an interesting new angle for evaluating existing gravity theories, and it may even give us a small hint on how to combine quantum gravity with Newton and Einstein gravity.

The present study examined and compared the effects of high- and low-molecular weight (MW) chitosan, a nutraceutical, on intestinal and liver lipid metabolism in rats fed with high-fat diet. Both high- and low-MW chitosan decreased liver weight, elongated small intestine, improved the dysregulation of blood lipids and liver fat accumulation, and increased fecal lipid excretion in high-fat diet-fed rats. Supplementation of both high- and low-MW chitosan significantly inhibited the decreased phosphorylated AMP-activated protein kinase (AMPK)α and peroxisome proliferator-activated receptor (PPAR)α protein expressions and the increased lipogenesis/cholesterogenesis-associated protein expressions (sterol regulatory element binding protein (SREBP)1c, SREBP2, and PPARγ) and the decreased apolipoprotein (Apo)E and microsomal triglyceride transfer protein (MTTP) protein expressions in the livers of high-fat diet-fed rats. Both high and low-MW chitosan supplementation could also suppress the increased MTTP protein expression and the decreased angiopoietin-like protein (Angptl)4 protein expression in the intestines of high-fat diet-fed rats. Comparison between high and low-MW chitosan, high-MW chitosan has a higher efficiency than low-MW chitosan on the inhibition of intestinal lipid absorption and the increase of hepatic fatty acid oxidation, which can improve liver lipid biosynthesis and accumulation.

The use of pain relief during castration and dehorning of calves on commercial beef operations can be limited by constraints associated with the delivery of analgesic agents. As topical anaesthetic (TA) and buccal meloxicam (MEL) are now available in Australia, offering practical analgesic treatments for concurrent castration and dehorning of beef calves, a study was conducted to determine their efficacy in providing pain relief when applied alone or in combination. Weaner calves were randomly allocated to; (1) no castration and dehorning / positive control (CONP); (2) castration and dehorning / negative control (CONN); (3) castration and dehorning with buccal meloxicam (BM); (4) castration and dehorning with topical anaesthetic (TA); and (5) castration and dehorning with buccal meloxicam and topical anaesthetic (BMTA). Weight gain, paddock utilisation, lying activity and behaviour following treatment were measured. CONP and BMTA calves had significantly greater weight gain than CONN calves (P < 0.001). CONN calves spent less time lying compared to BMTA calves on all days (P < 0.001). All dehorned and castrated calves spent more time walking (P = 0.024) and less time eating (P < 0.001) compared to CONP calves. There was a trend for CONP calves to spend the most time standing and CONN calves to spend the least time standing (P = 0.059). There were also trends for the frequency of head turns to be lowest in CONP and BMTA calves (P = 0.098) and tail flicks to be highest in CONN and BM calves (P = 0.061). The findings of this study suggest that TA and MEL can improve welfare and production of calves following surgical castration and amputation dehorning.

Agavins consumption has lead to accelerate body weight loss in mice. We investigated the changes on cecal microbiota and short chain fatty acids (SCFA) associated to body weight loss in overweight mice. Firstly, mice were fed with standard (ST5) or high fat (HF5) diet for 5 weeks. Secondly, overweight mice were shifted to standard diet alone (HF-ST10) or supplemented with agavins (HF-ST+A10) or oligofructose (HF-ST+O10), five more weeks. Cecal contents were collected before and after supplementation to determine microbiota and SCFA concentrations. At the end of first phase, HF5 mice showed a significant increase of body weight, which was associated with reduction of cecal microbiota diversity (PD whole tree; non-parametric t-test, P < 0.05), increased Firmicutes/Bacteroidetes ratio and reduced SCFA concentrations (t-test, P < 0.05). After diet shifted, HF-ST10 normalized its microbiota, increase its diversity and SCFA levels, whereas agavins (HF-ST+A10) or oligofructose (HF-ST+O10) led to partial microbiota restoration, with normalization of the Firmicutes/Bacteroides ratio as well as higher SCFA levels (P < 0.1). Moreover, agavins noticeably enriched Klebsiella and Citrobacter (LDA > 3.0); this enrichment has not been reported previously under a prebiotic treatment. In conclusion, agavins or oligofructose modulated cecal microbiota composition, reduced extent of diversity and increased SCFA. Furthermore, identification of bacteria enriched by agavins, opens opportunities to explore new probiotics.

Human serum albumin (HSA) is multifunctional protein, known to be a natural carrier for a number of endogenous and exogenous compounds, including drugs. Formulating anticancer drugs with HSA is a clinically validated approach to improve the pharmacological properties and provide targeted delivery (passive and active) of cytotoxic payload to the tumor (such as in Abraxane). A number of receptors facilitating HSA uptake from systemic circulation have been characterized. What is interesting, such uptake may differ depending on the nature and quantity of ligands bound to HSA. Based on this, one might like to modify the HSA in a way that its distribution is more favorable for certain therapeutic purposes, thus ensuring more efficient delivery of the therapeutic cargo to disease site. E.g. Levofloxacin (LV), broad spectrum antibiotic drug, could benefit from extended systemic exposure, and stronger interaction with plasma proteins could be useful for this purpose. We have engrafted monomeric or polymeric CDs on the surface of HSA molecules to strengthen the LV adsorption (CD-LV dissociation constant is three orders of magnitude lower than that for HSA-LF). We have found that (HSA-HPolS)conj+LV exhibited the highest activity against E. coli, whereas (HSA-HPCD)conj+LV was the most effective against B. subtilis; and both HSA conjugates were more potent than LV alone or LV with HSA. Further fine-tuning of HSA could yield an improvement in biodistribution, and thus a more favorable risk/benefit ratio.

A form of dementia distinct from healthy cognitive aging, Alzheimer's disease (AD) is a complex multi-stage disease that currently afflicts over 50 million people worldwide. Unfortunately, previous therapeutic strategies developed from murine models emulating different aspects of AD pathogenesis have failed. Consequently, researchers are now developing models that express several aspects of pathogenesis that better reflect the clinical situation in humans. As such, this review seeks to provide insight regarding current applications of mammalian models in AD research by addressing recent developments and characterizations of prominent transgenic models and their contributions to pathogenesis as well as discuss the advantages, limitations, and application of emerging models (hAβ-KI) that better capture genetic heterogeneity and mixed pathologies observed in the clinical situation.

(1) Background: Heart failure (HF) is the final stage of multiple cardiac diseases, which has now become a severe public health problem worldwide. β-Adrenergic receptor (β-AR) overactivation is a major pathological factor associated with multiple cardiac diseases and mediates cardiac fibrosis and inflammation. Previous study has demonstrated that Bruton's tyrosine kinase (BTK) mediated cardiac fibrosis by TGF-β related signal pathways, indicating that BTK was a potential drug target for cardiac fibrosis. Zanubrutinib, a second-generation BTK inhibitor, has shown anti-fibrosis effects in previous research. However, it is unclear whether Zanubrutinib can alleviate cardiac fibrosis induced by β-AR overactivation;(2) Methods: In vivo: Male C57BL/6J mice were treated with or without the β-AR agonist isoproterenol (ISO) to establish cardiac fibrosis animal model. Here, results showed that BTK inhibitor Zanubrutinib (ZB) had a great effect on cardiac fibrosis and inflammation induced by β-AR. In vitro: Results showed that ZB alleviated β-AR-induced cardiac fibroblast activation and macrophage proinflammatory cytokine production. Further mechanism studies demonstrated that ZB inhibited β-AR-induced cardiac fibrosis and inflammation by BTK、STAT3、NF-κB and PI3K/Akt signal pathways both in vivo and in vitro; (4) Conclusions: our research provides evidence that ZB ameliorates β-AR-induced cardiac fibrosis and inflammation.

3,4-Dihydroquinolin-2(1H)-ones represent a class of valuable bioactive compounds with six-membered nitrogen-containing heterocyclic structures. The development of simple, mild and efficient synthetic methods has been widely concerned by synthetic chemists. In this review, we have summarized a series of different synthetic strategies for the synthesis of dihydroquinoline-2(1H)-ones via catalytic annulation of α,β-unsaturated N-arylamides in the past decade, including covering electrophilic cyclization, radical initiated cyclization and photochemical cyclization reactions. Besides, the substrate scope and mechanistic details are also discussed. This paper will provide a useful reference for the development of diverse synthesis methodologies of 3,4-dihydroquinolin-2(1H)-ones.

Cancer stem cells (CSCs) are a tumor cell subpopulation that drives tumor progression and metastasis, leading to poor overall survival of patients. In colorectal cancer (CRC), hyper-activation of Wnt/β-catenin signaling by mutation of both Adenomatous polyposis coli (APC) and K-Ras increases the size of the CSC population. We previously showed that the CPD0857 inactivates Wnt/β-catenin signaling by promoting ubiquitin-dependent proteasomal degradation of β-catenin and Ras proteins, thereby decreasing proliferation and increasing apoptosis of CRC lines. CPD0857 also decreased growth and invasiveness of CRC cells harboring mutant K-Ras resistant to EGFR mAb therapy. Here, we show that CPD0857 treatment decreases proliferation and increases neuronal differentiation of neural progenitor cells (NPCs). CDP0857 effectively reduced expression of CSC markers and suppressed self-renewal capacity. CPD0857 treatment also inhibited proliferation and expression of CSC markers in D-K-Ras MT cells carrying K-Ras, APC and PI3K mutations, indicating inhibition of PI3K/AKT signaling. Moreover, CPD0857-treated xenograft mice showed regression of tumor growth and decreased numbers of CSCs in tumors. We conclude that CPD0857 could serve as the basis of a drug development strategy targeting CSCs activated through Wnt/β-catenin-Ras MAPK-PI3K/AKT signaling in CRCs.