Search

Simple Summary: In this study, we conducted genome-wide copy number variation (CNV) analysis using next-generation sequencing data from Large White (LW) and Minzhu (MZ) pigs and integrated transcriptomic data from dorsal adipose tissues of 180-day-old LW and MZ pigs for expression quantitative trait loci (eQTL) analysis. Among the identified CNVs, the transforming growth factor beta receptor 3 (TGFBR3) gene was found to be associated with back fat thickness (BFT), with a dose effect observed between the TGFBR3 gene at the genomic and transcriptomic levels. In vitro experiments further demonstrated that TGFBR3 expression is involved in the proliferation and differentiation of porcine preadipocytes. BFT is closely related to meat quality and lean meat percentage in pigs. The BFT traits of European LW pigs significantly differ from those of Chinese indigenous fatty MZ pigs. CNV is a prevalent genetic variation that plays an important role in economically important traits in pigs. However, the potential contribution of CNV to BFT in LW and MZ pigs remains unclear. In this study, whole-genome CNV detection was performed using next-generation sequencing data from LW and MZ pigs, and transcriptome data from back fat tissue of 180-day-old LW and MZ pigs were integrated for expression quantitative trait loci (eQTL) analysis. We identified a copy number variation in the TGFBR3 gene associated with BFT, showing a dose effect between the genome and transcriptome levels of the TGFBR3 gene. In porcine preadipocytes, TGFBR3 expression continuously increased during differentiation. Knockdown of TGFBR3 using specific siRNA inhibited preadipocyte differentiation and proliferation. Our study provides insights into the genetic regulation of pork quality and offers a theoretical basis for improving carcass quality by modulating BFT in pigs. [ABSTRACT FROM AUTHOR]

Purpose: Palliative radiotherapy (RT) plays a crucial role in alleviating symptoms associated with metastatic sarcoma. However, there is a lack of consensus on the optimal palliative radiation dose and fractionation for metastatic sarcomas. We analyzed the association between biologically effective radiation dose and symptom response for patients who underwent palliative RT for metastatic sarcomas Methods and materials: We retrospectively identified patients with metastatic sarcoma treated with palliative RT between 1999 and 2021 at our institution. We assessed the association between equivalent dose in 2 Gy fractions (EQD2) with an α/β of three and symptom relief or overall survival (OS) using univariable and multivariable analyses. Results: Of the 198 metastatic sites treated, the most common indications for palliative radiation were pain (n = 181, 91 %) and compression of adjacent structures (n = 16, 8 %). In our analysis, an EQD2 of > 20 Gy was associated with greater rates of short-term symptom relief (n = 143, 85 %) at the RT site compared to an EQD2 of ≤ 20 Gy (n = 14, 54 %, P = 0.001) with no reports of grade 3 or higher toxicity. However, there was no significant improvement in short-term symptom relief for higher radiation doses. Patients treated with an EQD2 of ≤ 20 Gy had a significantly worse performance status, but there was no significant difference in overall survival based on EQD2 on multivariable analysis. Conclusions: An EQD2 ≤ 20 Gy (e.g., 8 Gy in 1 fraction) provided inadequate palliative benefit in this series. An EQD2 > 20 Gy resulted in greater rates of symptom palliation in metastatic sarcomas, but further dose escalation did not improve symptom response or durability. These findings suggest standard palliative regimens such as 20 Gy in 5 fractions (EQD2 of 28 Gy) are effective for patients with metastatic sarcomas.

Objective To monitor the effectiveness and accuracy of the blood transfusion compatibility test system by self-made weakly positive internal quality control products. Methods Red blood cells from DAT(-) healthy subjects were selected, and B/RhD(-)E(-) red blood cells were selected as tube 1. A/RhD(+ )E(+ ) was selected as tube 2 to prepare blood group quality control products according to the principle of blood group antigen compatibility, and red blood cell preservation solution and corresponding ABO blood group reagent antibody were added to make the agglutination intensity of microcolumn gel method in reverse blood typing reach a low positive value (1+ ). Tube 3 and tube 4 were prepared with five different preservation media: plasma, serum, antibody diluent, mixture of equal plasma and antibody diluent, and mixture of equal serum and antibody diluent, respectively. IgM anti-E antibody was added to tube 3, and IgG anti-D antibody was added to tube 4, so that the agglutination intensity of microcolumn gel method reached a low positive value (1+ ). Results Comparison between the 5 different preservation media showed that the preservation medium of antibody diluent was the most stable for weakly positive antibody (F=11.35, P

5‐Aminolevulinic acid (ALA) is a prodrug for protoporphyrin IX (PpIX)‐mediated photodynamic therapy (PDT) and fluorescence‐guided tumor surgery. We previously reported that lapatinib, a repurposed ABCG2 inhibitor, enhanced ALA‐induced PpIX fluorescence and PDT by blocking ABCG2‐mediated PpIX efflux. In the present study, we evaluated how the variation in ABCG2 activities/protein levels affected tumor cell response to the enhancement of PpIX/PDT by lapatinib and Ko143, an ABCG2 tool inhibitor. ABCG2 activities and protein levels were determined in a panel of human cancer cell lines. Effects of lapatinib and Ko143 on enhancing ALA‐PpIX fluorescence and PDT were evaluated and correlated with tumor cell ABCG2 activities. We found that both lapatinib and Ko143 enhanced ALA‐PpIX fluorescence and PDT in a dose‐dependent manner, although lapatinib exhibited lower efficacy and potency than Ko143 in nearly all cancer cell lines. The EC50 of ABCG2 inhibitors for enhancing ALA‐PpIX and PDT had a positive correlation with tumor cell ABCG2 activities, indicating that tumor cell lines with lower ABCG2 activities were more sensitive to ABCG2 inhibitors for PpIX/PDT enhancement. Our results suggest that, for optimal therapeutic enhancement, the dose of ABCG2 inhibitors needs to be tailored based on the ABCG2 expression/activity in tumors. [ABSTRACT FROM AUTHOR]

BFT is closely related to meat quality and lean meat percentage in pigs. The BFT traits of European LW pigs significantly differ from those of Chinese indigenous fatty MZ pigs. CNV is a prevalent genetic variation that plays an important role in economically important traits in pigs. However, the potential contribution of CNV to BFT in LW and MZ pigs remains unclear. In this study, whole-genome CNV detection was performed using next-generation sequencing data from LW and MZ pigs, and transcriptome data from back fat tissue of 180-day-old LW and MZ pigs were integrated for expression quantitative trait loci (eQTL) analysis. We identified a copy number variation in the TGFBR3 gene associated with BFT, showing a dose effect between the genome and transcriptome levels of the TGFBR3 gene. In porcine preadipocytes, TGFBR3 expression continuously increased during differentiation. Knockdown of TGFBR3 using specific siRNA inhibited preadipocyte differentiation and proliferation. Our study provides insights into the genetic regulation of pork quality and offers a theoretical basis for improving carcass quality by modulating BFT in pigs.

Introduction: The Republic of North Macedonia and especially the field pit of Polog in terms of geographical position and climatic aspect is considered as a place with different variables such as: temperature, humidity, radioactive exposure, hilly-mountainous relief. The Sharr mountain in the west and the dry mountain in the north, limit the Polog field pit in all directions, such as north-west and south-east, causing the living environment to deteriorate in the winter period due to air, water and land pollutants. With special emphasis, we highlight the winter season when we have an alarming state of air pollution, such as certain regions of the Republic of North Macedonia and especially the region of the field pit of Polog with the cities of Tetovo and Gostivar and the surrounding area. Recently, the city of Tetova and its surroundings is considered one of the most polluted cities in the country, region and the largest in the world, then this phenomenon of pollution necessarily leads us to unwanted consequences for the population that lives and operates in this region. As a result of environmental factors such as air pollution and other related factors such as: stress, temperature, food, social genes, mental state and other related factors can lead to disorders in the human body and lead to diseases that attack the nervous and cardiovascular systems, skeletal and thyroid. Many studies talk about the alarming condition of patients who are affected by these diseases, therefore our paper will focus on the effect of these factors above all on the actual state of pollutants in the Polog region of North Macedonia. The purpose of the study: This paper aims to investigate the potential causes that can affect the health of the population of the Polog field pit and especially the city of Tetova and its surroundings. As a potential pollutants of the living environment, the following can be considered: carbon monoxide, carbon dioxide, sulfur dioxide, urban combustion from automobiles, combustion of various physical substances, chemical components from factories, smoke from chimneys from burning oil and coal, combustion from wood in the form of pellets, etc. Material and working method: In the study, fertilized chicken eggs were taken and incubated in the incubator for 21 days of incubation. The eggs were treated with different doses of air pollutant extract at certain stages of embryonic development. Using the stereomicroscope with macroscopic and microscopic method were analyzed ontogenetic changes in certain stages of embryonic development. Research results: The results of the research will give a real insight into the situation of the level of pollution of the living environment in the city of Tetovo and its surroundings and in the field pit of Pollog. The monitoring of the living environment can be followed by the treatment of air pollutants in certain doses in the form of ampoule therapy, and the negative effect of the given dose on the hen's eggs will be observed. All eggs with the highest dose of injection had a stagnated embryonic development, whereas egss with lower dose of injections had underdeveloped embryos. Conclusion: From the results of the research we can conclude that the potential pollutants from air pollutants can lead to consequences for the population living in this region but also for the living world in general. These factors can lead to disorders of the nervous system, cardiovascular, and thyroid disorders and other respiratory diseases. This research will give a real insight into the pollution of the living environment and the possible consequences of this at a local, regional and wid er level. [ABSTRACT FROM AUTHOR]

Introduction: Various studies have shown that the effects of the action of drugs, in addition to having positive effects, they can also provoke negative effects in different organs of the body, where by giving more doses in some cases it can exceed the therapeutic limit and become toxic and produce pathological effects in both experimental animals and humans. Uncontrolled use and drug overdose can lead to macroscopic histopathological changes and give teratogenic, mutagenic and carcinogenic effects. Purpose of the paper: This paper aims to study the effects of some drugs at different stages of embryonic development in chicken eggs. The research of this paper will consist of the toxic effect of drugs and macroscopic and microscopic histopathological changes in certain stages of embryonic development of chicken eggs. Material and method: In the study, fertilized chicken eggs were taken and incubated in the incubator for 21 days of incubation. The eggs were treated with the antibiotic gentamicin at certain stages of embryonic development. The eggs hatched on day thirteen, day fifteen, eighteen and day twentyone. Using the stereomicroscope with the macroscopic and microscopic method were analyzed ontogenetic changes in certain stages of embryonic development. Results: The given dose of the antibiotic gentamicin can have negative effects in certain stages of embryonic development in chicken eggs. The dose given in ampullary form in certain quantities to chicken eggs has inhibited and stagnated the processes of embryonic development at different stages compared to control eggs. Conclusion: The given dose of gentamicin can stagnate embryonic development in certain stages and can provoke changes in certain stages of embryonic development. This phenomenon encourages us to do even more detailed research in this direction to see the effect of the given dose and to analyze what consequences it can provoke overdoses at different stages of embryonic development and within the organism. The lethal dose applied at certain stages of ontogenesis may have lethal consequences for the chick embryo at certain stages of embryonic development. [ABSTRACT FROM AUTHOR]

Grapholita molesta (Busck) is an important pest of pear trees. Numerous esters accumulate consistently in mature pear fruits. However, little is known about the effects of single esters from pear fruits at different concentrations on the responses of male and female G. molesta. In this study, the responses of virgin males, virgin females, and gravid females to five esters (3‐methylbutyl acetate, ethyl hexanoate, ethyl butanoate, butyl acetate, and hexyl acetate) of pear fruits at three dosage levels (1, 5 and 10 μg/μL) were investigated using electroantennography (EAG), wind tunnel experiments, and field tests. Our results showed that ethyl butanoate (5 μg/μL) elicited higher EAG responses in virgin females and males than a mixture of all five volatiles, and elicited an equal EAG response to that for the mixture in gravid females, with all responses to ethyl butanoate and the mixture being higher than the response to hexane alone. For upwind flight, ethyl butanoate (5 μg/μL) excited equal moth flight–location behavior in virgin and gravid females to that for the mixture, which were both higher than the response to hexane. For close flight, ethyl hexanoate (5 μg/μL) and 3‐methylbutyl acetate (10 μg/μL) appeared to be the activating compounds, eliciting equal responses from virgin females to that of the mixture, and higher responses of gravid females to that of the mixture, both of which were higher than the responses to hexane. Upwind and close flight responses of virgin males were lower than those of virgin and gravid females. In field trials, we verified that traps baited with ethyl butanoate (5 μg/μL) captured more moths than the other esters. Therefore, from the esters and concentrations tested, we recommend ethyl butanoate (5 μg/μL) for potential use as an attractant for G. molesta in orchards. [ABSTRACT FROM AUTHOR]

Ketamine has been abused as a psychedelic agent and causes diverse neurobehavioral changes. Adolescence is a critical developmental stage but vulnerable to substances and environmental stimuli. Growing evidence shows that ketamine affects glutamatergic neurotransmission, which is important for memory storage, addiction, and psychosis. To explore diverse biological responses, this study was designed to assess ketamine sensitivity in mice of different ages and strains. Male C57BL/6J and BALB/c mice were studied in adolescence and adulthood separately. An open field test assessed motor behavioral changes. After a 30-min baseline habituation, mice were injected with ketamine (0, 25, and 50 mg/kg), and their locomotion was measured for 60 min. Following ketamine injection, the travelled distance and speed significantly increased in C57BL/6J mice between both age groups (p < 0.01), but not in BALB/c mice. The pattern of hyperlocomotion showed that mice were delayed at the higher dose (50 mg/kg) compared to the lower dose (25 mg/kg) of ketamine treatment. Ketamine accentuated locomotor activation in adolescent C57BL/6J mice compared to adults, but not in the BALB/c strain. Here, we show that ketamine-induced locomotor behavior is modulated by dose and age. The discrepancy of neurobehaviors in the two strains of mice indicates that sensitivity to ketamine is biologically determined. This study suggests that individual vulnerability to ketamine's pharmacological responses varies biologically. [ABSTRACT FROM AUTHOR]

In animal models, melanocyte-stimulating hormones (MSHs) protect the liver from various injuries. Erythropoietic protoporphyria (EPP), a metabolic disorder, leads to the accumulation of protoporphyrin (PPIX). In addition to the most prominent symptom of incapacitating phototoxic skin reactions, 20% of EPP patients exhibit disturbed liver functioning and 4% experience terminal liver failure caused by the hepatobiliary elimination of excess PPIX. Skin symptoms are mitigated through the application of the controlled-release implant afamelanotide, an α-MSH analog, every sixty days. Recently, we showed that liver function tests (LFTs) improved during afamelanotide treatment when compared to before treatment. The present study investigated whether this effect is dose-dependent, as the evidence of dose dependency would support a beneficial influence of afamelanotide. Methods: In this retrospective observational study, we included 2933 liver-function tests, 1186 PPIX concentrations and 1659 afamelanotide implant applications in 70 EPP patients. We investigated whether the number of days since the preceding afamelanotide dose or the number of doses during the preceding 365 days had an effect on LFTs and PPIX levels. In addition, we assessed the effect of global radiation. Results: Inter-patient differences exerted the most prominent effect on PPIX and LFTs. In addition, PPIX increased significantly with an increase in the number of days since the last afamelanotide implant (p < 0.0001). ALAT and bilirubin decreased significantly with an increasing number of afamelanotide doses in the preceding 365 days (p = 0.012, p = 0.0299, respectively). Global radiation only influenced PPIX (p = 0.0113). Conclusions: These findings suggest that afamelanotide ameliorates both PPIX concentrations and LFTs in EPP in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

In the context of lifetime extension of Nuclear Power Plants (NPPs), electric cable ageing has to be checked to evaluate their performance during normal operation. These electric cables are complex materials, with a conductor and insulating shield in the metal and insulating layer and sheath in the polymer; the most sensitive layer is commonly considered to be the insulating layer. The ageing mechanism upon irradiation under oxidative conditions has been evaluated using gas mass spectrometry and the first conclusions have been drawn. Nonetheless, the data obtained are very numerous and complex; thus, the objective of this new article regards these experimental results using mathematical tools. It allowed confirmation of all the results obtained on these materials, but using chemometrics, i.e., statistical/mathematical analyses, of the results. Using these powerful mathematical tools gives strength to the analyses realised and to the conclusions obtained. [ABSTRACT FROM AUTHOR]

Bone defects are difficult to heal, which conveys a heavy burden to patients' lives and their economy. The total flavonoids of Rhizoma drynariae (TFRD) can promote the osteogenesis of distraction osteogenesis. However, the dose effect is not clear, the treatment period is short, and the quality of bone formation is poor. In our study, we observed the long‐term effects and dose effects of TFRD on bone defects, verified the main ingredients of TFRD in combination with network pharmacology for the first time, explored its potential mechanism, and verified these findings. We found that TFRD management for 12 weeks regulated osteogenesis and angiogenesis in rats with 4‐mm tibial bone defects through the PI3K/AKT/HIF‐1α/VEGF signaling pathway, especially at high doses (135 mg kg−1 d−1). The vascularization effect of TFRD in promoting human umbilical vein endothelial cells was inhibited by PI3K inhibitors. These results provide a reference for the clinical application of TFRD. [ABSTRACT FROM AUTHOR]

Salt and alkaline stress is one of the important problems restricting agricultural production and afforestation projects. This kind of stress will greatly limit the growth and development of forest trees. Recently, melatonin has been gradually realized as a strong kind of antioxidant due to its important regulatory and protective roles in the process of plant growth and development. This study takes Xin Lin 1 (Populus cathayana × canadansis 'Xin Lin 1') as the research object, and measures the changes of physiological indexes at different time points to verify the alleviation effect of melatonin under salt and alkaline stress. In this experiment, plants have different behaviors in the face of different levels of exogenous melatonin. Among them, low concentrations of melatonin (50 μM and 100 μM) were more helpful to reduce the levels of MDA and osmotic regulators in leaves. At this level, the SOD and CAT content in the leaves increased significantly. Melatonin at 800 μM was more inclined to induce POD, but its activity was not significantly induced. Overall, melatonin contributes to the secretion of ABA in plants and has a tendency to inhibit the content of SA. It is worth mentioning that the 100 μM melatonin treatment was more conducive to the secretion of IAA. To sum up, this experiment proves that melatonin has a dose effect in alleviating stress. [ABSTRACT FROM AUTHOR]

Plant somatic cells can reprogram into differentiated embryos through somatic embryogenesis (SE) on the condition of plant growth regulators (PGRs). RNA sequencing analysis was performed to investigate transcriptional profiling on cotton redifferentiated callus that was induced by different auxin types (IAA and 2,4-D), different concentrations (0, 0.025, and 0.05 mg L−1), and different incubation times (0, 5, and 20 days). Under the 2,4-D induction effect, signal transduction pathways of plant hormones were significantly enriched in the embryogenic response stage (5 days). These results indicated that auxin signal transduction genes were necessary for the initial response of embryogenic differentiation. In the pre-embryonic initial period (20 days), the photosynthetic pathway was significantly enriched. Most differentially expressed genes (DEGs) were downregulated under the induction of 2,4-D. Upon the dose effect of IAA and 2,4-D, respectively, pathways were significantly enriched in phenylpropanoid biosynthesis, fatty acid metabolism, and carbon metabolic pathways. Therefore, primary and secondary metabolism pathways were critical in cotton SE. These results showed that complex synergistic mechanisms involving multiple cellular pathways were the causes of the induction and dose effect of auxin-induced SE. This study reveals a systematic molecular response to auxin signals and reveals the way that regulates embryogenic redifferentiation during cotton SE. [ABSTRACT FROM AUTHOR]

The breakpoint (BP) of the progressive ratio (PR) schedule of drug delivery is a commonly used estimate of the drug abuse liability and is interpreted as a measure of motivation to get the next dose. This study investigated BP as a product of the rate of response and the duration of lever-pressing activity. The results were not consistent with the conventional interpretation. Rats were trained to self-administer cocaine intravenously under the fixed ratio (FR1) and PR schedules of delivery. The rate of lever presses and the duration of activity before the last self-injection of different cocaine unit doses and before the last press under the PR schedule were analyzed. The rate of presses was independent of the cocaine unit dose and the duration of activity was proportional to the dose. We assume that BP is a measure of the drug's overall ability to maintain self-administration under the PR schedule. Therefore, the proportionality between the dose and BP is not evidence of a stronger reinforcing effect of higher doses but the result of cocaine level staying longer within the range of cocaine concentrations (the compulsion zone) capable of inducing lever presses. The relationship between the cocaine unit dose and BP does not represent the dose magnitude of the effect function but the dose duration of the effect function. [ABSTRACT FROM AUTHOR]

Abstract Background The hippocampus is a critical organ for irradiation. Thus, we explored changes in hippocampal volume according to the dose delivered and the location relative to the glioblastoma. Methods All patients were treated for glioblastoma with surgery, concomitant radiotherapy and temozolomide, and adjuvant temozolomide. Hippocampi were retrospectively delineated on three MRIs, performed at baseline, at the time of relapse, and on the last MRI available at the end of follow-up. A total of 98, 96, and 82 hippocampi were measured in the 49 patients included in the study, respectively. The patients were stratified into three subgroups according to the dose delivered to 40% of the hippocampus. In the group 1 (n = 6), the hippocampal D40% was 7.4 Gy. Results Regardless of the time of measurement, homolateral hippocampal volumes were significantly lower than those contralateral to the tumor. Regardless of the side, the volumes at the last MRI were significantly lower than those measured at baseline. There was a significant correlation among the decrease in hippocampal volume regardless of its side, and Dmax (p = 0.001), D98% (p = 0.028) and D40% (p = 0.0002). After adjustment for the time of MRI, these correlations remained significant. According to the D40% and volume at MRIlast, the hippocampi decreased by 4 mm3/Gy overall. Conclusions There was a significant relationship between the radiotherapy dose and decrease in hippocampal volume. However, at the lowest doses, the hippocampi seem to exhibit an adaptive increase in their volume, which could indicate a plasticity effect. Consequently, shielding at least one hippocampus by delivering the lowest possible dose is recommended so that cognitive function can be preserved. Trial registration Retrospectively registered.

Xylooligosaccharide (XOS) is an attractive prebiotic mainly due to its bifidogenic effect. However, commercial XOS with different compositions is often applied in the food industry at different doses without specifications. In this study, we evaluated the bifidogenic activity of XOS at different doses with either mixtures or pure fractions with different degrees of polymerization (DP), using three strains of Bifidobacterium spp., including B. breve ATCC 15700, B. bifidum ATCC 29521, and B. animalis subsp. lactis HN019. Three growth indicators showed strain-specific bifidogenic activity of XOS, and the activity was both dose- and fraction-dependent as only certain fractions stimulated significant growth. Adding 0.25% XOS (w/v) also promoted increase in total bifidobacterial population of rat fecal samples fermented in vitro. Albeit the antibacterial activity of XOS fractions can be demonstrated, significant growth inhibition can only be achieved when 4.0% XOS mixture was added in Staphylococcus aureus ATCC 6538 pure culture. In contrast, in the presence of B. lactis HN019, 1.0% XOS showed significant antibacterial activity against S. aureus ATCC 6538 in milk. In addition, RNA sequencing suggested downregulation of genes involved in S. aureus ATCC 6538 infection, pathogenesis, and quorum sensing, by XOS. In conclusion, the report urges scientific specifications on XOS chemistry for its effective application as a novel food ingredient or functional food and provides novel insights into its bifidogenic and antibacterial activities.

Abstract Background Birds have various plumage color patterns, and spot is a common phenotype. Herein, we conducted genome-wide association studies (GWAS) in a population of 225 ducks with different sized black spots to reveal the genetic basis of this phenomenon. Results First, we quantified the black spot phenotype within the duck population. The results showed that the uncolored area of the body surface first appeared on the ventral side. With increasing duck age, the area of the black spots was highly conserved across the whole body surface. The GWAS results identified a 198 kb (Chr4: 10,149,651 bp to 10,348,068 bp) genetic region that was significantly associated with the black spot phenotype. The conditional GWAS and linkage disequilibrium (LD) analysis further narrowed the ultimate candidate region to 167 kb (Chr4: 10,180,939 bp to 10,348,068 bp). A key gene regulating melanoblast migration and differentiation, EDNRB2 (Endothelin B receptor-like), was found in the candidate region and having significant mRNA expression level changes in embryonic duck skin tissue with different spot sizes. The significant SNPs (single nucleotide polymorphisms) associated with the EDNRB2 gene were annotated, and two mutations (Chr4: 10,180,939 T > C and Chr4: 10,190,671 A > T) were found to result in the loss of binding sites for two trans-factors, XBP1 and cMYB. The phenotypic effect of these two mutations suggested that they can regulate the size of black spots in a dose-dependent manner, and Chr4: 10,180,939 T > C was the major allele locus. Conclusions Our results revealed that EDNRB2 was the gene responsible for the variation in duck body surface spot size. Chr4: 10,180,939 T > C was the major allele that explained 49.5 % (dorsal side) and 32.9 % (ventral side) of the variation in duck body surface spot size, while 32.1 % (dorsal side) and 19.1 % (ventral side) of the variation could be explained by Chr4: 10,190,671 A > T. The trans-factor prediction also suggested that XBP1 and cMYB have the potential to interact with EDNRB2, providing new insights into the mechanism of action of these genes.

In animal models, melanocyte-stimulating hormones (MSHs) protect the liver from various injuries. Erythropoietic protoporphyria (EPP), a metabolic disorder, leads to the accumulation of protoporphyrin (PPIX). In addition to the most prominent symptom of incapacitating phototoxic skin reactions, 20% of EPP patients exhibit disturbed liver functioning and 4% experience terminal liver failure caused by the hepatobiliary elimination of excess PPIX. Skin symptoms are mitigated through the application of the controlled-release implant afamelanotide, an α-MSH analog, every sixty days. Recently, we showed that liver function tests (LFTs) improved during afamelanotide treatment when compared to before treatment. The present study investigated whether this effect is dose-dependent, as the evidence of dose dependency would support a beneficial influence of afamelanotide. Methods: In this retrospective observational study, we included 2933 liver-function tests, 1186 PPIX concentrations and 1659 afamelanotide implant applications in 70 EPP patients. We investigated whether the number of days since the preceding afamelanotide dose or the number of doses during the preceding 365 days had an effect on LFTs and PPIX levels. In addition, we assessed the effect of global radiation. Results: Inter-patient differences exerted the most prominent effect on PPIX and LFTs. In addition, PPIX increased significantly with an increase in the number of days since the last afamelanotide implant (p < 0.0001). ALAT and bilirubin decreased significantly with an increasing number of afamelanotide doses in the preceding 365 days (p = 0.012, p = 0.0299, respectively). Global radiation only influenced PPIX (p = 0.0113). Conclusions: These findings suggest that afamelanotide ameliorates both PPIX concentrations and LFTs in EPP in a dose-dependent manner.

This study aimed to quantitatively compare the efficacy of fluticasone furoate (FF) and fluticasone propionate (FP) in adolescents and adults with asthma. We searched the PubMed and EMBASE databases for placebo‐controlled trials that met the inclusion criteria. Pharmacodynamic models were established to describe the time–course of the primary outcome (trough forced expiratory volume in the first second [FEV1]). Secondary outcomes (asthma symptoms, quality of life and exacerbations) were also compared via a meta‐analysis. A total of 14 articles were included in the analysis, involving 6640 subjects. The efficacy plateau of the two drugs could be reached in 2 weeks. The changes from the baseline in trough FEV1 (95% CI) at week 2 of FF at 200 and 100 μg/day were 0.168 L (0.064–0.199) and 0.127 L (0.048–0.163), respectively. The changes from the baseline in trough FEV1 (95% CI) at week 2 of FP at 1000, 500, 250 and 100 μg/day were 0.133 L (0.049–0.171), 0.127 L (0.043–0.163), 0.117 L (0.039–0.150) and 0.093 L (0.032–0.129), respectively. The efficacy of FP had reached a plateau at the maximum evaluated dose (1000 μg/day), while a plateau effect was not seen at the maximum evaluated dose of FF (200 μg/day). In terms of secondary outcomes, the relative effects of the two drugs relative to the placebo were similar and did not show obvious dose–effect relationships. In this study, the time–course and dose–effect characteristics of FP, FF and placebo were quantitatively evaluated, providing necessary quantitative information for asthma‐related guidelines. [ABSTRACT FROM AUTHOR]

Many quinoline (QL) derivatives are present in the environment and pose potential threats to human health and ecological safety. The acute toxicity of 30 haloquinolines (HQs) was examined using the photobacterium Vibrio fischeri. IC50 values (inhibitory concentration for 50% luminescence elimination) were in the range 5.52 to >200 mg·L−1. The derivative 5-BrQL exhibited the highest toxicity, with 3-ClQL, 3-BrQL, 4-BrQL, 5-BrQL, 6-BrQL, and 6-IQL all having IC50 values below 10 mg·L−1. Comparative molecular field analysis modeling based on the steric and electrostatic field properties of the HQs was used to quantify the impact of halogen substituents on their toxicity. QL derivative rings with larger substituents at the 2/8-positions and less negative charge at the 4/5/6/8-positions were positively correlated with acute toxicity towards V. fischeri. [ABSTRACT FROM AUTHOR]

Grapholita molesta (Busck) is a menacing pest of fruit trees worldwide. A mixture of glucose, acetic acid, ethanol, and water (GAEWM) has been widely used for monitoring or trapping G. molesta adults. Previous research has shown that acetic acid captures more moths compared to ethanol; however, the respective roles of acetic acid and ethanol in bisexual attraction remain unknown. This study investigated the olfactory behaviours of virgin females, virgin males, and gravid females to variations in nine concentration levels of acetic acid (A) and ethanol (E) for GAEWM using electroantennography, a wind tunnel experiment, and a field test. There was a significant dose‐dependent response by moths to the GAEWM lure variations that affected the range of lure detection and the probability of a moth being trapped. In contrast, adult sex and mating status had the strongest effect on the behaviours associated with flying close to the trap. For medium level dosages of A and E, one combination with acetic acid exceeding ethanol content (A > E; #3, A:E = 3:1) elicited antennal detection by the test adults, and upwind flight of the females. In another combination with ethanol predominating (E > A; #7, A:E = 1:3), the lured traps caught more males than control groups. For low dosages, with the acetic acid level equal to ethanol (A = E; #1, A:E = 1:1), females flew upwind, and virgin females flew around the lure. For high level dosages, with A > E (#6, A:E = 3:2), the antennae of gravid females and virgin males reacted to the lure. These results concluded that the acetic acid to ethanol ratios of either 3:1 or 1:3 in GAEWM has the potential to improve the attraction of both G. molesta sexes to traps. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that psilocybin has antidepressant effects. In the current study, we aim to explore the dose effects of psilocybin on primary (major depression patients) and secondary depression (depressed cancer patients).Methods: Published studies concerning psilocybin for depression were retrieved. In accordance with PRISMA guidelines, 6 databases (PubMed, Embase, Web of Science, Cochrane Library, Clinicaltrials.gov 2.3 and WanFang database) were searched for research studies published or still in progress from inception to 30 November, 2020, with language restricted to English and Chinese. Hedges' g of Beck Depression Inventory (BDI) score changes was calculated as the primary outcome.Results: 7 articles were finally included, with a total of 136 participants. In terms of efficacy, Hedges' g was 1.289 (95%CI=[1.020, 1.558], heterogeneity I2=50.995%, p<0.001). As psilocybin dose increases within a certain range, the antidepressive effect declines and then increases, with 30-35 mg/70 kg achieving the optimal therapeutic effect. Subgroup analysis suggested that the antidepressive effect of psilocybin was extremely significant at a relatively high dose (30-35mg/70kg: Hedges' g=3.059, 95%CI=[2.269, 3.849], p<0.001), long-term (>1month: Hedges' g=1.123, 95%CI=[0.861, 1.385], p<0.001) and when used in primary depression patients (Hedges' g=2.190, 95%CI=[1.423, 2.957], p<0.001).Limitations: Only a small number of studies can be identified of variable quality, thus our conclusions remain preliminary.Conclusions: Our preliminary results have shown that psilocybin exerts a rapid effect in reducing depressive symptom on primary and secondary depression. The optimal dose of psilocybin may be 30-35mg/70kg or higher; future clinical trials are warranted for further evaluation on its effect. [ABSTRACT FROM AUTHOR]

Abstract Background Changes in the esophageal microbiome correlate with esophageal disease, but the effects of proton pump inhibitor (PPI) drugs are incompletely characterized. Our objective was to identify the effects of PPI use on the microbial community of the esophagus. Methods Mucosal biopsies of the distal esophagus were analyzed using a customized esophageal microbiome qPCR panel array (EMB). Patient demographics, use of PPIs, duration of use and dose were recorded. Results Fifty-eight patients were included. Mean age was 60.5 years. Ninety percent (52/58) of patients were on PPIs. Mean dose was 42.7 mg. Mean duration of use was 2.5 years. The use of PPIs led to a significant difference in absolute levels of only one organism, Actinomyces, in the entire array (p

Background We conducted a matched case–control study in China during the 2013/14–2015/16 influenza seasons to estimate influenza vaccine effectiveness (VE) by dose among children aged 6 months to 8 years. Methods Cases were laboratory-confirmed influenza infections identified through the influenza-like illness sentinel surveillance network in Guangzhou. Age- and sex-matched community controls were randomly selected through the expanded immunization program database. We defined priming as receipt of ≥1 dose of influenza vaccine during the immediate prior season. Results In total, 4,185 case–control pairs were analyzed. Among children 6–35 months, VE for current season dose(s) across the three seasons during 2013/14–2015/16 were 59% (95% Confidence Interval: 44–71%), 12% (−11%,30%), 54% (32–69%); among unprimed children 6–35 months, VE for 1 vs 2 current season doses were 45% (8–67%) vs 65% (46–78%), −2% (−53%,32%) vs 19% (−11%,40%), and 37% (−24%,68%) vs 61% (32–78%). Among children aged 3–8 years, VE for current season dose(s) across study seasons were 62% (36–78%), 43% (22–58%), 32% (1–53%). VE for unprimed children receiving 1 dose only in current season was insignificant or lower than among all children. Conclusion Findings support utility of providing second dose (“booster dose”) of seasonal influenza vaccine to unprimed children aged 6–35 months, and the need to study further dose effect of a booster dose among unprimed children aged 3–8 years in China.

Double-mutant heat-labile toxin (dmLT, LTR192G/L211A) of enterotoxigenic Escherichia coli (ETEC) is an effective mucosal adjuvant. Recent studies have shown that dmLT also exhibits adjuvanticity for antigens administered parenterally. In this study, we subcutaneously (SC) immunized mice with the ETEC adhesin-based vaccine, CFA/I/II/IV MEFA (multiepitope fusion antigen), adjuvanted with dmLT and examined the impact of dmLT on antibody responses specific to the seven adhesins in the vaccine construction [CFA/I, CFA/II (CS1, CS2, CS3) and CFA/IV (CS4, CS5, CS6)]. Mice were immunized with a fixed dose of CFA/I/II/IV MEFA and ascending doses of dmLT adjuvant (0, 0.05, 0.1, 0.5 or 1.0 µg) to assess the potential dmLT dose response relationship. Data showed that dmLT enhanced systemic antibody responses to all seven antigens (CFA/I, CS1-CS6) targeted by MEFA in a dose-dependent way. The adjuvant effect of dmLT on the MEFA construct plateaued at a dose of 0.1 µg. Results also indicated that dmLT is an effective parenteral adjuvant when given by the SC route with the ETEC adhesin MEFA vaccine and that antibody enhancement was achieved with relatively low doses. These observations suggest the potential usefulness of dmLT for parenteral ETEC vaccine candidates and also perhaps for vaccines against other pathogens.

Many studies have demonstrated that long double-stranded RNAs (dsRNAs) targeting essential genes of white spot syndrome virus (WSSV) can induce a sequence-specific antiviral RNA interference (RNAi) response in shrimp, thereby offering protection against WSSV infection. However, further experimental data on the required dose of dsRNAs and the duration of protection from a single administration are necessary to establish RNAi-mediated methods as effective and practical antiviral measures. In this study, we evaluated the protective efficacy and the duration of protection provided by a single administration of various doses of long dsRNA targeting WSSV ribonucleotide reductase 2 (rr2) in white-leg shrimp Litopenaeus vannamei. The protective efficacy of long dsRNA targeting WSSV rr2 was not diminished by the reduction of the dose to 100 ng g-1 of body weight, suggesting that a relatively low dose can effectively induce an RNAi response in shrimp. Furthermore, shrimp were well-protected against WSSV challenges for up to 4 wk post-administration of the rr2-targeting long dsRNA, although the protective effect almost disappeared at 6 wk post-administration. These results suggest that long dsRNAs can provide protection against WSSV for at least 1 mo, and monthly administration of long dsRNAs could serve as a long-term protective strategy for shrimp against WSSV.

Purpose: Palliative radiotherapy (RT) plays a crucial role in alleviating symptoms associated with metastatic sarcoma. However, there is a lack of consensus on the optimal palliative radiation dose and fractionation for metastatic sarcomas. We analyzed the association between biologically effective radiation dose and symptom response for patients who underwent palliative RT for metastatic sarcomas., Methods and Materials: We retrospectively identified patients with metastatic sarcoma treated with palliative RT between 1999 and 2021 at our institution. We assessed the association between equivalent dose in 2 Gy fractions (EQD2) with an α/β of three and symptom relief or overall survival (OS) using univariable and multivariable analyses., Results: Of the 198 metastatic sites treated, the most common indications for palliative radiation were pain (n = 181, 91 %) and compression of adjacent structures (n = 16, 8 %). In our analysis, an EQD2 of > 20 Gy was associated with greater rates of short-term symptom relief (n = 143, 85 %) at the RT site compared to an EQD2 of ≤ 20 Gy (n = 14, 54 %, P = 0.001) with no reports of grade 3 or higher toxicity. However, there was no significant improvement in short-term symptom relief for higher radiation doses. Patients treated with an EQD2 of ≤ 20 Gy had a significantly worse performance status, but there was no significant difference in overall survival based on EQD2 on multivariable analysis., Conclusions: An EQD2 ≤ 20 Gy (e.g., 8 Gy in 1 fraction) provided inadequate palliative benefit in this series. An EQD2 > 20 Gy resulted in greater rates of symptom palliation in metastatic sarcomas, but further dose escalation did not improve symptom response or durability. These findings suggest standard palliative regimens such as 20 Gy in 5 fractions (EQD2 of 28 Gy) are effective for patients with metastatic sarcomas., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: E.J.M. has served as a paid consultant for Guidepoint and GLG. The other authors declare no competing interests., (© 2024 The Author(s).)

Recent studies in cognitively unimpaired elderly individuals suggest that the APOE ε4 allele exerts a dosage-dependent effect on brain tau deposition. The aim of this study was to investigate sex differences in APOE ε4 gene dosage effects on brain tau deposition in cognitively impaired individuals using quantitative 18F-flortaucipir PET. Preprocessed 18F-flortaucipir tau PET images, T1-weighted structural MRI, demographic information, global cortical amyloid-β burden measured by 18F-florbetapir PET, CSF total tau and phosphorylated tau measurements were obtained from the Alzheimer's Disease Neuroimaging Initiative database. Two hundred and sixty-eight cognitively impaired individuals with 146 APOE ε4 non-carriers and 122 carriers (85 heterozygotes and 37 homozygotes) were included in the study. An iterative reblurred Van Cittert iteration partial volume correction method was applied to all downloaded PET images. Magnetic resonance images were used for PET spatial normalization. Twelve regional standardized uptake value ratios relative to the cerebellum were computed in standard space. APOE ε4 dosage × sex interaction effect on 18F-flortaucipir standardized uptake value ratios was assessed using generalized linear models and sex-stratified analysis. We observed a significant APOE ε4 dosage × sex interaction effect on tau deposition in the lateral temporal, posterior cingulate, medial temporal, inferior temporal, entorhinal cortex, amygdala, parahippocampal gyrus regions after adjusting for age and education level (P < 0.05). The medial temporal, entorhinal cortex, amygdala and parahippocampal gyrus regions retained a significant APOE ε4 dosage × sex interaction effect on tau deposition after adjusting for global cortical amyloid-β (P < 0.05). In sex-stratified analysis, there was no significant difference in tau deposition between female homozygotes and heterozygotes (P > 0.05). In contrast, male homozygotes standardized uptake value ratios were significantly greater than heterozygotes or non-carriers throughout all 12 regions of interest (P < 0.05). Female heterozygotes exhibited significantly increased tau deposition compared to male heterozygotes in the orbitofrontal, posterior cingulate, lateral temporal, inferior temporal, entorhinal cortex, amygdala and parahippocampal gyrus (P < 0.05). Results from voxel-wise analysis were similar to the ones obtained from regions of interest analysis. Our findings indicate that an APOE ε4 dosage effect on brain region-specific tau deposition exists in males, but not females. These results have important clinical implications towards developing sex and genotype-guided therapeutics in Alzheimer's disease and uncovers a potential explanation underlying differential APOE ε4-associated Alzheimer's risk in males and females. [ABSTRACT FROM AUTHOR]

In the context of lifetime extension of Nuclear Power Plants (NPPs), electric cable ageing has to be checked to evaluate their performance during normal operation. These electric cables are complex materials, with a conductor and insulating shield in the metal and insulating layer and sheath in the polymer; the most sensitive layer is commonly considered to be the insulating layer. The ageing mechanism upon irradiation under oxidative conditions has been evaluated using gas mass spectrometry and the first conclusions have been drawn. Nonetheless, the data obtained are very numerous and complex; thus, the objective of this new article regards these experimental results using mathematical tools. It allowed confirmation of all the results obtained on these materials, but using chemometrics, i.e., statistical/mathematical analyses, of the results. Using these powerful mathematical tools gives strength to the analyses realised and to the conclusions obtained.

Human exposure to bisphenols has rarely been reported. The most important challenges in this regard are the sensitivity and accuracy of the analytical methods employed. Dansyl chloride derivatization prior to high‐performance liquid chromatography–tandem mass spectrometry has been prevalently employed to improve sensitivity. However, the dose effect of the derivatization reagent on the reaction products is not well understood, especially for reactants with two or more active groups. This study investigated the mass ratio of dansyl chloride to bisphenols and found the mass ratio played a vital role in changing the composition of derivatives; further, the optimal ratio for obtaining di‐substituted derivatives was confirmed. Under optimal conditions, solid‐phase extraction followed by dansyl chloride derivatization coupled with high‐performance liquid chromatography–tandem mass spectrometry was used to detect eight bisphenols in human serum samples. The method detection limits of the eight bisphenols were 0.025‒0.28 ng/mL, and the recoveries were 72.9‒121.7% by spiking bisphenols (2, 5, and 20 ng/mL) into bovine serum. The detection frequencies of bisphenol A and bisphenol F in 73 serum samples obtained from children from Guangzhou were 41.1% and 71.2%, respectively, while the detection frequencies of other bisphenols were below 20%. The concentrations of bisphenol A and bisphenol F were < 0.28‒8.0 ng/mL and < 0.028‒7.6 ng/mL, respectively. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Chinese Institute of Food Science & Technology is the property of Journal of Chinese Institute of Food Science & Technology Periodical Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The hippocampus is a critical organ for irradiation. Thus, we explored changes in hippocampal volume according to the dose delivered and the location relative to the glioblastoma.Methods: All patients were treated for glioblastoma with surgery, concomitant radiotherapy and temozolomide, and adjuvant temozolomide. Hippocampi were retrospectively delineated on three MRIs, performed at baseline, at the time of relapse, and on the last MRI available at the end of follow-up. A total of 98, 96, and 82 hippocampi were measured in the 49 patients included in the study, respectively. The patients were stratified into three subgroups according to the dose delivered to 40% of the hippocampus. In the group 1 (n = 6), the hippocampal D40% was < 7.4 Gy, in the group 2 (n = 13), only the Hcontra D40% was < 7.4 Gy, and in the group 3 (n = 30), the D40% for both hippocampi was > 7.4 Gy.Results: Regardless of the time of measurement, homolateral hippocampal volumes were significantly lower than those contralateral to the tumor. Regardless of the side, the volumes at the last MRI were significantly lower than those measured at baseline. There was a significant correlation among the decrease in hippocampal volume regardless of its side, and Dmax (p = 0.001), D98% (p = 0.028) and D40% (p = 0.0002). After adjustment for the time of MRI, these correlations remained significant. According to the D40% and volume at MRIlast, the hippocampi decreased by 4 mm3/Gy overall.Conclusions: There was a significant relationship between the radiotherapy dose and decrease in hippocampal volume. However, at the lowest doses, the hippocampi seem to exhibit an adaptive increase in their volume, which could indicate a plasticity effect. Consequently, shielding at least one hippocampus by delivering the lowest possible dose is recommended so that cognitive function can be preserved. Trial registration Retrospectively registered. [ABSTRACT FROM AUTHOR]

BACKGROUND: A large number of studies believe that exercise can ameliorate the disease course of Alzheimer’s disease mice, but some studies hold different views. It is unclear whether there is a certain dose relationship between exercise and the improvement of the disease course in Alzheimer’s disease mice. OBJECTIVE: To evaluate the dose-effect relationship between exercise and improvement of the disease course in Alzheimer’s disease mice, and to obtain a relatively definite exercise dose threshold. METHODS: Web of Science Core Collection, PubMed, and CNKI were searched for relevant literature using the keywords of “exercise; running; Alzheimer’s diseases; AD; mice” in English and Chinese, respectively. Then the included literature were logically analyzed and reviewed. RESULTS AND CONCLUSION: There was a certain dose-effect relationship between exercise and improvement of disease course in Alzheimer’s disease mice. The disease course of Alzheimer’s disease mice could be improved only when the average speed of voluntary wheel running was greater than 2.5 m/min, no less than 12 hours a day, 7 days per week, for no less than 3 continuous weeks in total as well as when the speed of treadmill running was more than 10 m/min, no less than 5 days per week, for no less than 9 weeks. However, there is still a lot of work to be done to better determine the dose effect of exercise and its threshold. [ABSTRACT FROM AUTHOR]

Sulphurous acid derived from sulfur dioxide (SO2 ) emission leads to the pollution of irrigation water and the inhibition of plant growth. The safe concentration threshold of NaHSO3 in plants should be clarified to promote agricultural production. In this study, Orychophragmus violaceus seedlings were used as experimental materials and five NaHSO3 concentrations (i.e., 0, 1, 2, 5, 10 mmol·L −1 ) were simultaneously sprayed on the leaf surface of different seedlings separately. Leaf physiology responses under different concentrations were analyzed. The NaHSO3 did not promote photosynthesis in O. violaceus under the 1 and 2 mmol·L −1 treatments. It was conducive to the net photosynthetic rate (PN), photorespiration rate (Rp), chlorophyll content, actual photochemical quantum yield (YII) and photochemical quenching (qP) under the 5 mmol·L −1 treatment. However, quantum yield of regulated energy dissipation (YNPQ) and nonphotochemical quenching (NPQ) were inhibited. Under the 10 mmol·L −1 treatment, PN, chlorophyll content, YII, qP, dark respiration rate (Rd ) and electron transport rate (ETR) showed significant decreases, while the photorespiration portion (Sp) significantly increased. Our results demonstrated that NaHSO3 provided a sulfur source for plant growth and interfered with the redox reaction of the plant itself, and its role as a photorespiratory inhibitor might be masked. [ABSTRACT FROM AUTHOR]

Abstract Background To evaluate the impact of radiation dose on overall survival (OS) in patients treated with adjuvant chemoradiation (CRT) for pancreatic ductal adenocarcinoma (PDAC). Methods A multicenter retrospective analysis on 514 patients with PDAC (T1–4; N0–1; M0) treated with surgical resection with macroscopically negative margins (R0–1) followed by adjuvant CRT was performed. Patients were stratified into 4 groups based on radiotherapy doses (group 1:

Salt and alkaline stress is one of the important problems restricting agricultural production and afforestation projects. This kind of stress will greatly limit the growth and development of forest trees. Recently, melatonin has been gradually realized as a strong kind of antioxidant due to its important regulatory and protective roles in the process of plant growth and development. This study takes Xin Lin 1 (Populus cathayana × canadansis ‘Xin Lin 1’) as the research object, and measures the changes of physiological indexes at different time points to verify the alleviation effect of melatonin under salt and alkaline stress. In this experiment, plants have different behaviors in the face of different levels of exogenous melatonin. Among them, low concentrations of melatonin (50 μM and 100 μM) were more helpful to reduce the levels of MDA and osmotic regulators in leaves. At this level, the SOD and CAT content in the leaves increased significantly. Melatonin at 800 μM was more inclined to induce POD, but its activity was not significantly induced. Overall, melatonin contributes to the secretion of ABA in plants and has a tendency to inhibit the content of SA. It is worth mentioning that the 100 μM melatonin treatment was more conducive to the secretion of IAA. To sum up, this experiment proves that melatonin has a dose effect in alleviating stress.

The purpose of this study was to analyze the time course and dose effect from metformin on body mass index (BMI) in children and adolescents by model-based meta-analysis (MBMA). Searching randomized controlled trial (RCT) studies of metformin on BMI in children and adolescents. The change rates of BMI from baseline values were used as indicator of evaluating metformin efficacy. A total of 18 RCT studies, 1,228 children and adolescents, were included for analysis, including patients with obesity, patients with type 1 diabetes mellitus, patients with nonalcoholic fatty liver, and patients with precocity. In order to achieve better effect of metformin on BMI in children and adolescents, the present study recommended that for patients with obesity, 1,000 mg/day metformin was required for at least 15.2 weeks and 60.8 weeks to achieve the plateau of metformin effect; for patients with type 1 diabetes mellitus, 1,000 mg/day metformin was required for at least 25.2 weeks and 100.8 weeks to achieve the plateau of metformin effect; for patients with nonalcoholic fatty liver, 1,000 mg/day metformin was required for at least 6.57 weeks and 26.28 weeks to achieve the plateau of metformin effect; for patients with precocity, 425 mg/day metformin was required for at least 12.4 weeks and 49.6 weeks to achieve the plateau of metformin effect. It was the first time to analyze the time course and dose effect from metformin on BMI and to recommend dosage and duration of treatment for metformin in children and adolescents with different disease types.

Background: Birds have various plumage color patterns, and spot is a common phenotype. Herein, we conducted genome-wide association studies (GWAS) in a population of 225 ducks with different sized black spots to reveal the genetic basis of this phenomenon. Results: First, we quantified the black spot phenotype within the duck population. The results showed that the uncolored area of the body surface first appeared on the ventral side. With increasing duck age, the area of the black spots was highly conserved across the whole body surface. The GWAS results identified a 198 kb (Chr4: 10,149,651 bp to 10,348,068 bp) genetic region that was significantly associated with the black spot phenotype. The conditional GWAS and linkage disequilibrium (LD) analysis further narrowed the ultimate candidate region to 167 kb (Chr4: 10,180,939 bp to 10,348,068 bp). A key gene regulating melanoblast migration and differentiation, EDNRB2 (Endothelin B receptor-like), was found in the candidate region and having significant mRNA expression level changes in embryonic duck skin tissue with different spot sizes. The significant SNPs (single nucleotide polymorphisms) associated with the EDNRB2 gene were annotated, and two mutations (Chr4: 10,180,939 T > C and Chr4: 10,190,671 A > T) were found to result in the loss of binding sites for two trans-factors, XBP1 and cMYB. The phenotypic effect of these two mutations suggested that they can regulate the size of black spots in a dose-dependent manner, and Chr4: 10,180,939 T > C was the major allele locus. Conclusions: Our results revealed that EDNRB2 was the gene responsible for the variation in duck body surface spot size. Chr4: 10,180,939 T > C was the major allele that explained 49.5 % (dorsal side) and 32.9 % (ventral side) of the variation in duck body surface spot size, while 32.1 % (dorsal side) and 19.1 % (ventral side) of the variation could be explained by Chr4: 10,190,671 A > T. The trans-factor prediction also suggested that XBP1 and cMYB have the potential to interact with EDNRB2, providing new insights into the mechanism of action of these genes. [ABSTRACT FROM AUTHOR]

Aims: The current study aimed to evaluate the dose effect of a temporary tissue expander (TTE) according to the radiotherapy technique for breast cancer patients. Materials and methods: Computed tomography images of a 3D-printed breast phantom with a TTE were acquired for dosimetric analysis. For dose measurement during 180 cGy of radiotherapy, 13 EBT3 films were attached to the TTE while including the metal port area. Treatment planning was performed for three-dimensional conformal radiotherapy (3DCRT), field-in-field radiotherapy, intensity-modulated radiotherapy (IMRT), and volumetric modulated arc therapy (VMAT) while considering whether a bolus was used and whether artifacts were corrected. The difference at each point between the measured mean and calculated doses was analyzed to determine the association with the radiotherapy techniques. Results: The effect of the metal port on the radiation dose was associated with the treatment technique. The dose difference between the measured and calculated doses was 6.8% (191.6 cGy vs. 179.5 cGy) for cases treated with 3DCRT with bolus and artifact correction. The dose difference for cases treated with VMAT and 3DCRT without bolus and with artifact correction was 5.8% (190.2 cGy vs. 179.8 cGy) and 5.6% (193.3 cGy vs. 183.1 cGy), respectively. IMRT with the bolus showed a minimum difference of 0.3% (180.7 cGy vs. 181.3 cGy). Conclusion: The presence of the metal port within the TTE in radiation fields resulted to insignificant increased dose differences according to the treatment technique. Future studies should assess whether this dose difference could affect clinical outcomes. [ABSTRACT FROM AUTHOR]

What is known and objectives: Tacrolimus is used to treat patients with lupus nephritis; however, its time course and dose effect on proteinuria in lupus nephritis patients remain unknown. The purpose of this study was to determine the time course and dose effect of tacrolimus on proteinuria in lupus nephritis patients via model‐based meta‐analysis (MBMA). Methods: PubMed, Web of Science, Cochrane Library and ClinicalTrials.gov databases were systematically searched for information on the efficacy of tacrolimus against proteinuria in lupus nephritis patients. Useful data were extracted to build a model for the population studied using a non‐linear mixed‐effect model (NONMEM). This model was applied to simulate time course of tacrolimus on proteinuria using Monte Carlo simulations. Results: Ten clinical studies that recruited 222 patients with lupus nephritis were included. Based on various diagnostic plots, we found that the established model described the observed data reasonably well. In addition, the typical Emax and ET50 of tacrolimus for 24‐hour proteinuria in lupus nephritis patients were −5.88 g and 0.37 months, respectively. The baseline value of 24‐hour proteinuria affected Emax. No significant dose‐response relationship was observed in the range of tacrolimus concentration used in the present study (3‐10 ng/mL), indicating that the effect of tacrolimus on proteinuria depends on effective concentration range and not the dose. However, the time course relationship was obvious; the efficacy of tacrolimus increased over time, reaching a plateau (80% Emax) at approximately 1.48 months from the beginning of treatment. What is new and conclusion: When the concentration range of tacrolimus is maintained at 3‐10 ng/mL, at least 1.48 months of treatment is required to achieve a better outcome with regard to proteinuria in lupus nephritis patients. [ABSTRACT FROM AUTHOR]

The remediation of metal(loid) contaminated sites often requires the application of an amendment, such as biochar. Biochar is the product of biomass pyrolysis and has been shown to reduce soil acidity, immobilize metal(loid)s and thus ameliorate plant growth. The beneficial effects of biochar are usually higher at a higher dose. However, an excessive dose can have negative outcomes due to nutrient loss. The application of an amendment to the soil comes at a financial cost, especially if the contaminated area is large, and therefore the optimum dose must be determined. In addition, to overcome the cost of biochar application, the use of a plant with economic benefits, such as flax, can be a suitable option. In this context, a mesocosm study, on a former mining soil polluted by As and Pb was performed, using flax and biochar applied at increasing concentrations. Results showed an increase in soil pH and the immobilization of Pb with increasing biochar doses. These ameliorations led to better plant growth. A higher biochar dose increased plant growth up to a 3% application rate, from which point dry weight no longer increased.Metal(loid) concentrations decreased between 1 and 3% biochar, and then increased at higher doses. It can thus be concluded that with 3% biochar, soil properties are ameliorated, metal(loid)s are immobilized, and plant growth increases, and a higher biochar application rate does not bring about better outcomes. Therefore, a 3% biochar application dose seems to be the best application dose to improve soil conditions and plant growth at a lower cost. Article Highlights: Application dose of a lightwood biochar was tested on a former mine soil A higher biochar dose led to increased soil condition improvements Flax growth improved up to 3% biochar then decreased The optimum biochar dose was determined to be 3% [ABSTRACT FROM AUTHOR]

The functionality of electric cables, being the safety components of plants, has to be ensured. In nuclear power plants, when they are in the reactor building, these cables can suffer γ irradiation even in normal operating conditions. Their ageing behaviour needs to be well understood to be able to determine a precise end-of-life criterion. As polymers are the most radiosensitive material of the cables, this paper focuses on the ageing of this kind of material and, more specifically, on the ageing of silane-crosslinked polyethylenes (XLPEs). XLPEs are now one of the most employed polymers to manufacture cables. We performed irradiation under oxidative conditions of several model silane-crosslinked polyethylenes with different additives and filler: at three different doses (0, 67, 220 and 374 kGy) for one dose rate (78 Gy·h−1) and at one dose (67 kGy) for three dose rates (8.5, 78 and 400 Gy·h−1). Modifications in the organic materials were followed by X-ray photoelectron spectroscopy. This analytical technique allows following the evolution of the different chemical products formed under irradiation. A better understanding at the atomic scale of the effect of additives on the degradation of polymers is proposed as a function of the ageing conditions.

Allium species and their organosulfur-derived compounds could prevent obesity and metabolic dysfunction, as they exhibit immunomodulatory and antimicrobial properties. Here, we report the anti-obesogenic potential and dose-dependent effects (0.1 or 1 mg/kg/day) of propyl propane thiosulfinate (PTS) in a murine model of diet-induced obesity. The obesogenic diet increased body weight gain and adipocyte size, and boosted inflammatory marker (Cd11c) expression in the adipose tissue. Conversely, PTS prevented these effects in a dose-dependent manner. Moreover, the higher dose of PTS improved glucose and hepatic homeostasis, modulated lipid metabolism, and raised markers of the thermogenic capacity of brown adipose tissue. In the colon, the obesogenic diet reduced IL-22 levels and increased gut barrier function markers (Cldn3, Muc2, Reg3g, DefaA); however, the highest PTS dose normalized all of these markers to the levels of mice fed a standard diet. Gut microbiota analyses revealed no differences in diversity indexes and only minor taxonomic changes, such as an increase in butyrate producers, Intestimonas and Alistipes, and a decrease in Bifidobacterium in mice receiving the highest PTS dose. In summary, our study provides preclinical evidence for the protective effects of PTS against obesity, which if confirmed in humans, might provide a novel plant-based dietary product to counteract this condition.

Background and Objective: Patients with oropharyngeal carcinoma (OPC) often have difficulty swallowing, which may affect quality of life (QoL). Radiation dose to constrictor muscles plays an important role.Methods: 54 patients with locally advanced OPC were evaluated after intensity-modulated radiotherapy. Data were collected at standardized intervals using the EORTC questionnaires QLQ-C30 and QLQ-HN35 within two years. The pharyngeal constrictors (superior, middle, and inferior) were each contoured as an organ at risk. Influence of dose to the constrictors (≥55 Gy vs. <55 Gy) on late dysphagia and QoL was analyzed using the t‑test.Results: Late radiation-induced dysphagia depends significantly on the dose to the lower pharyngeal constrictor. At a dose of ≥55 Gy, 14 (64%) patients developed dysphagia grade ≤2 and 8 (36%) patients grade ≥3. At a dose of <55 Gy, the distribution at the end of radiotherapy (RT) was similar: 22 (69%) patients with dysphagia grade ≤2, 10 (31%) with grade ≥3. There was no dose-dependent difference in the severity of dysphagia in the acute phase (p = 0.989). There were differences 18 months after the end of RT: ≥55 Gy: 19 (86%) patients showed dysphagia grade ≤2; 3 (14%) grade ≥3. At <55 Gy, 31 (97%) patients developed grade ≤2, 1 (3%) grade ≥3 (18 months: p = 0.001; 24 months: p = 0.000). Late dysphagia is also dependent on the dose level of the middle constrictor muscle (6 months: p = 0.000; 12 months: p = 0.005, 18 months: p = 0.034). After 24 months, there was no significant difference (p = 0.374).Conclusion: Radiation dose to the upper constrictor muscle appears to be of little relevance. The middle and lower constrictor should be given special consideration to avoid late dysphagia. Long-term QoL is independent on radiation dose. [ABSTRACT FROM AUTHOR]

This study aimed to explore the protective potential of influenza vaccination against occurrence of dementia in patients with chronic obstructive pulmonary disease (COPD), who are expected to be more vulnerable to influenza infection. This nationwide retrospective cohort study enrolled patients with COPD (aged ≥60 years) from 1 January 2001 to 31 December 2012 by using the Taiwan National Health Insurance Research Database. By applying time-dependent Cox proportional hazard model, we used multivariate analysis to calculate the adjusted HR (aHR) with 95% CI of dementia in relation to influenza vaccination among patients with COPD. Besides, patients were partitioned into four groups according to the vaccination number (unvaccinated, 1, 2-3 and ≥4 total vaccinations) to investigate the dose-response effect of vaccinations on the dementia incidence. This cohort study included 19 848 patients with COPD, and 45% of them received influenza vaccination. The aHR of dementia was 0.68 (95% CI: 0.62 to 0.74, p<0.001) comparing vaccinated patients with unvaccinated ones. Furthermore, there was a trend of dementia risk reduction with the vaccination number. For patients who received 2-3 vaccinations, the aHR was 0.81 (95% CI: 0.73 to 0.90), and for those received 4 vaccinations, the aHR was 0.44 (95% CI: 0.40 to 0.50), with p for trend <0.001. In conclusion, annual influenza vaccination can reduce the risk of dementia in patient with COPD in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

There is convincing clinical evidence to suggest that flavanol-containing foods/beverages are capable of inducing improvements in human vascular function. However, whilst (−)-epicatechin has been tested for efficacy, a full dose-dependency has yet to be established, particularly at doses below 1 mg/kg BW. The current study examined the dose-dependent effects of (−)-epicatechin on human vascular function with concurrent measurement of plasma (−)-epicatechin metabolites and levels of circulating nitrite and nitrate species, NO x. An acute, double-blind, placebo-controlled, crossover intervention trial was conducted in 20 healthy males with 4 treatment arms: water-based (−)-epicatechin (0.1, 0.5 and 1.0 mg/kg BW) and a water only as control. Vascular function was assessed by flow-mediated dilatation (FMD) measured at the brachial artery, laser Doppler imaging with iontophoresis (LDI) at the subcutaneous capillaries of the forearm (response to Ach and SNP) and peripheral blood pressure (BP) at baseline, 1, 2, 4 and 6 h post-intervention. Plasma analysis of epicatechin metabolites was conducted by LC-MS and circulating plasma of nitrite and nitrate species were performed using an HPLC-based system (ENO-30). Significant increases in % FMD were found to occur at 1 and 2 h following intake of 1 mg/kg BW, and at 2 h for the 0.5 mg/kg BW intake. There were no significant changes in LDI or BP at any time-points or intake levels. Increases in FMD over the 6 h timeframe were closely paralleled by the appearance of total plasma (−)-epicatechin metabolites. Non-significant changes in circulating NOx was observed. Our data add further evidence that (−)-epicatechin is a causal vasoactive molecule within flavanol-containing foods/beverages. In addition, we show for the first time that intake levels as low as 0.5 mg/kg BW are capable of inducing acute improvements in vascular function (FMD) in healthy volunteers. [ABSTRACT FROM AUTHOR]