(1) Background: Fire department cadets preparing to become firefighters and paramedics experience high levels of stress when participating in incidents like traffic accidents and fires. Stress adversely affects health and coping with it proves difficult. Unfortunately, there is no single method that reduces stress completely in humans. One non-invasive method for lowering stress hormone levels is craniosacral therapy. (2) Methods: Fifty-seven firefighting cadets aged 18-24 years (21.63 ± 1.41) participated in the study. They were randomly assigned to either a test group or a control group. Participants’ blood levels of cortisol and CRH (corticotropin-releasing hormone) were assessed before and after the study. The study group underwent 5-week craniosacral therapy (1x per week). (3) Results: The Kruskal-Wallis test showed that the therapy group’s result was statistically significant for CRH values (p-value=0.00067) and for cortisol values (p-value=<0.0001). Wilxocon and Dunn tests showed that statistical significance for cortisol after CS therapy between the control and study groups (p=0.0377), and for CRH between the control and study groups before (p=0.00634) and after the study (p=0.000887), and in the study group before and after the study (p=0.0101). (4) Conclusions: Five weeks of craniosacral therapy lowered stress hormone levels. This therapy is a non-invasive tool for reducing stress.

Purpose: Hormone Replacement Therapy (HRT), an FDA-approved treatment for menopausal conditions was found to be associated with increased risk of endometrial cancer and reduced oestrogen. Studies showing benefits of HRT in preventing chronic diseases lead to development of clinical guidelines by American College of Physicians. This study aims to assess effectiveness of HRT treatments across cardiometabolic measures including Triglycerides (TG), Follicle-Stimulating Hormone, LDL cholesterol, HDL cholesterol, and Estradiol in menopausal women. It reports gaps in scientific knowledge and clinical practice to enhance current guidelines and policies.Methods: A systematic methodology designed and published in PROSPERO (CRD42022346057) to report network meta-epidemiology analysis was utilised. We used databases by PubMed, Web of Science, ScienceDirect, EMBASE and MEDLINE for studies published between 30th of April 1980-2022. Effects of HRT treatments were explored using a mixed treatment comparison (MTC) model. Fixed and random-effects models were used to address heterogeneity in published studies. Publication bias was assessed and corrected using funnel plots and Egger’s test.Results: Of 45 eligible studies, our findings indicate a significant statistical heterogeneity between HRTs and reduction of TG, SFH, LDL-C alongside increase of HDL-C and Estradiol among menopausal women. The analysis suggests a lack of direct evidence to support their efficacy in reducing TG, SFH and LDL-C levels or to substantiate HRT’s effectiveness in increasing HDL-C and Estradiol. The results showed no significant publication bias in the meta-analysis of included studies.Conclusion: Our findings demonstrate that use of HRT interventions among menopausal women may reduce TG, FSH and LDL-C levels and increase levels of HDL-C and estradiol via oral and oral + transdermal administration. Our study reaffirms efficacy of HRT in supporting favourable lipid profile in menopausal women whilst highlighting the need for robust and inclusive epidemiology studies and clinical trials to further develop clinical guidelines and policies.

According to current guidelines, growth hormone (GH) therapy is strongly recommended in children and adolescents with GH deficiency (GHD) in order to accelerate growth rate and attain normal adult height. The diagnosis of GHD requires demonstration of decreased GH secretion in stimulation tests, below the established threshold value. Currently, GHD in children is classified as secondary insulin-like growth factor-1 (IGF-1) deficiency. Most of children diagnosed with isolated GHD presents with normal GH secretion at the attainment of near-final height or even in mid-puberty. The most important clinical problems, related to the diagnosis of isolated GHD in children and to optimal duration of rhGH therapy include: arbitrary definition of subnormal GH peak in stimulation tests, disregarding factors influencing GH secretion, insufficient diagnostic accuracy and poor reproducibility of GH stimulation tests, discrepancies between spontaneous and stimulated GH secretion, clinical entity of neurosecretory dysfunction, discrepancies between IGF-1 concentrations and results of GH stimulation tests, significance of IGF-1 deficiency for the diagnosis of GHD, a need for validation IGF-1 reference ranges. Many of these issues have remained unresolved for 25 years or even longer. It seems that finding solutions to them should optimize diagnostics and therapy of children with short stature.

Vitamin D deficiency and insufficiency are highly prevalent in CKD affecting over 80% of hemodialysis (HD) patients and require therapeutic intervention. Nephrological societies suggest the administration of cholecalciferol according to the guidelines for the general population. The aim of the observational study was to evaluate the efficacy and safety of the therapy with a high dose of cholecalciferol in HD patients with 25(OH)D deficiency and insufficiency to reach the target serum 25(OH)D level > 30 ng/mL. 22 patients (16 M), with an average age of 72.5 ± 13.03 years and 25(OH)D concentration of 13.05 (9.00–17.90) ng/mL were administered cholecalciferol at a therapeutic dose of 70,000 IU/week (20,000 IU + 20,000 IU + 30,000 IU, immediately after each dialysis session). All patients achieved the target value >30 ng/mL, with a mean time of 2.86 ± 1.87 weeks. In the first week, the target level of 25(OH)D (100%) was reached by 2 patients (9.09%), in the second week – by 15 patients (68.18%), in the fourth week – by 18 patients (81.18%) and in the ninth week by all 22 patients (100%). A significant increase in 1,25(OH)2D levels was observed during the study, however, only 2 patients (9.09%) achieved a concentration of 1,25(OH)2D above 25 ng/mL – the lower limit of the reference range. The intact PTH concentrations remained unchanged during the observation period. No episodes of hypercalcemia, and one new episode of hyperphosphatemia were observed. In conclusion, our study showed that the administration of a high therapeutic dose of cholecalciferol allowed for a quick, effective, and safe leveling of 25(OH)D concentration in HD patients.

Premature ovarian insufficiency (POI) is a highly prevalent disorder, characterized by the development of menopause before age of 40. Most cases are idiopathic; however, in some women the cause of this condition (e.g. anticancer treatment, genetic disorders, and enzymatic defects) may be identified. Although hormone replacement therapy, the principal therapeutic approach for POI, helps to alleviate the related symptoms, this does not effectively solve the issue of fertility. Assisted reproductive techniques also lack efficacy in these women. Thus, the effective approach to manage the patients with POI is highly warranted. Several mechanisms, associated with POI, have been identified, including lack of FSH receptor functioning, alterations in the apoptosis control, mutations in Sal-like 4 genes, thymulin or basonuclin-1 deficiency etc. The above-mentioned may be good targets for gene therapy in order to correct defects, leading to POI. The goal of this review is to summarize the current experience on the POI studies, that employed gene therapy, and to discuss the possible future directions in this field.

Sex dimorphism starts during early embryogenesis and is further manifested in response to hormones during puberty. As this leads to physical divergence that is measurably different between sexes, males enjoy physical performance advantages over females within competitive sport. While this advantage is the underlying basis of the segregation into male and female sporting categories, these sex-based categories do not account for transgender persons who experience incongruence between their biological sex and their experienced gender identity. Accordingly, the International Olympic Committee determined criteria by which a transgender woman may be eligible to compete in the female category, requiring total serum testosterone levels to be suppressed below 10 nmol/L for at least 12 months prior to and during competition. Whether this regulation removes the male performance advantage has not been collectively scrutinized. Here, we aim to review how differences in biological characteristics between biological males and females affect sporting performance and assess whether evidence exists to support the assumption that testosterone suppression in transgender women removes the male performance advantage. In this review, we report that the performance gap between males and females amounts to 10-50% depending on sport. The performance gap is more pronounced in sporting activities relying on muscle mass and strength, particularly in the upper body. Longitudinal studies examining the effects of testosterone suppression on muscle mass and strength in transgender women consistently show very modest changes, where the loss of lean body mass, muscle area and strength typically amounts to approximately 5% after 1 year of treatment. Thus, current evidence shows that the biological advantage enjoyed by transgender women is only minimally reduced when testosterone is suppressed. Sports organizations may therefore be compelled to reassess current policies regarding participation of transgender women in the female category of sport.

In individuals with spinal cord injury (SCI), rapid skeletal muscle atrophy and metabolic dysfunction pose profound rehabilitation challenges, often resulting in substantial loss of muscle mass and function. This study evaluates the effect of combined neuromuscular electrical stimulation (Comb-NMES) on skeletal muscle cross-sectional area (CSA) and inflammatory signaling within the acute phase of SCI. We applied a novel Comb-NMES regimen, integrating both high-frequency resistance and low-frequency aerobic protocols on the vastus lateralis muscle, to participants early post-SCI. Muscle biopsies were analyzed for CSA and inflammatory markers pre-and post-intervention. The results revealed a preservation of muscle CSA in the Comb-NMES group compared to a control group receiving transcutaneous electrical nerve stimulation and passive movements. Inflammatory signaling proteins such as TLR4 and Atrogin-1 were downregulated, whereas markers associated with muscle repair and growth were modulated beneficially in the Comb-NMES group. The study's findings suggest that early application of Comb-NMES post-SCI can attenuate inflammatory pathways linked to muscle atrophy and potentially promote muscle repair, advocating for its inclusion in early rehabilitation efforts. However, the small sample size and variability in injury characteristics emphasize the need for further research to corroborate these results across a more diverse and extensive SCI population.

Production of silkworm silk is the most economically important traits in the silk industry. Silk protein synthesis is regulated by juvenile hormone (JH) and 20-Hydroxyecdysone (20E). Therefore, it is important to understand the genetic regulation of silk production is thus a priority. JH binding protein (JHBP) transports JH from the hemolymph to target organs and cells and protects JH. In a previous study, we identified 41 genes containing a JHBP domain in the Bombyx mori genome. Only one JHBP gene, that is, BmJHBPd2, is highly expressed in the posterior silk gland (PSG) and its function remains unknown. In the present study, we investigated the expression levels of BmJHBPd2 and the major silk protein genes in the high silk-producing practical strain 872 (S872) and the low silk-producing local strain Dazao. Our results have shown that BmJHBPd2 was more highly expressed in S872, than in the Dazao strain, which is consistent with the expression pattern of fibroin genes. A subcellular localization assay indicated that BmJHBPd2 is located in the cytoplasm. In vitro hormone induction experiments showed that BmJHBPd2 was upregulated by treatment with juvenile hormone analogue (JHA). BmKr-h1 upregulation was significantly inhibited by overexpression of BmJHBPd2 at the cell level when induced by JHA. However, overexpression of BmJHBPd2 in the posterior silk gland by transgenic methods led to the inhibition of the expression of the silk fibroin gene, resulting in a reduction in silk yield. Further investigation has shown that in the BmJHBPd2OE individual, the key transcription factor Krüppel homolog 1 (Kr-h1) of the JH signaling pathway was inhibited, and 20E signaling pathway genes, such as broad complex (Brc), E74A, and ultraspiracle protein(USP), were upregulated. Our results have indicated that BmJHBPd2 plays an important role in the JH signaling pathway and was important for silk protein synthesis. Furthermore, our findings have helped to elucidate the mechanisms by which JH regulates silk protein synthesis.

Animals in human care are affected by stressors that can ultimately reduce fitness. When reproduction is affected, endangered species’ conservation programmes can be severely compromised. Thus, understanding factors related to stress and reproduction, and measures of related hormones, are important to ensure captive breeding success. Red pandas are endangered and populations in the wild are threatened with extinction. A global captive breeding programme has been launched to conserve the species with the goal of reintroduction. However there is little informaiton on how stressors impact reproductive aspects of the species. This study measured fecal glucocorticoid (fGCM), fecal progestagen (fPM) and fecal androgen (fAM) metabolite concentrations in 12 female and 8 male red pandas (Ailurus fulgens fulgens) at three zoos in northeastern India to determine predictors of adrenal and gonadal steroid activity and the influence of fGCM on reproduction. Results indicated that fGCM concentrations were higher in males than females, and positively correlated with number of visitors, while negatively related to frequency of feedings and enclosure area. Sex, visitor number, frequency of feeding, and enclosure area explained 67% of the variations in fGCM concentrations in the study population. Concentrations of fPM were positively associated with tree density in the enclosure, explaining 47% of the variation among females. For fAM, positive associations were found with frequency of feeding, but concentrations were negatively related to age and number of visitors; these three covariates explained 45% of the variation in fAM concentration among males. Comparison of fGCM with fPM showed a negative trend, indicating increasing adrenal hormones may decrease reproductive function among female red pandas. The study thus suggests that zoo management should consider increasing feeding frequency, providing larger enclosures with more trees, and regulating visitor numbers to reduce stress and increase reproductive fitness among red pandas.

Growth hormone (GH) is a peptide hormone that plays a crucial role in controlling growth, development, and lifespan. Molecular regulation of GH is accomplished via the GH receptor (GHR) gene, which is the main factor influencing human development and is essential to optimal functioning of the GH/IGF-I axis. Two GHR isoforms have been studied, according to the presence (flGHR) or absence (d3GHR) of exon 3. The d3GHR variant, which has recently been related to longevity, is associated with enhanced signal transduction and higher receptor function. Many of these studies indicated that the growth response to GH treatment may be affected. Individuals carrying the d3GHR isoform have higher receptor activity, improved signal transduction, and alterations in the treatment response and efficacy compared with those carrying the WT isoform. Further, studies performed in patients with acromegaly, Prader-Willi syndrome, Turner syndrome, small for gestational age (SGA), and growth hormone deficiency (GHD) suggested that the d3GHR variant may have an impact on the relationship between GH and IGF-I levels, height, weight, BMI, and other variables. Other research, however, revealed inconsistent results, which might have been caused by confounding factors, including limited sample sizes and different experimental methods. In this review, we lay out the complexity of the GHR isoforms and provide an overview of the major pharmacogenetic research conducted on this ongoing and unresolved subject.

Juvenile hormones (JH) play crucial roles in insect development, reproduction, and other physi-ological functions. Because JH is specific to arthropods, including insects, it has long been stud-ied for use in pest control. Accordingly, this study aimed to identify the substances that act as JH disruptors from edible plants. Curcuminoids generally exhibit a wide range of biological ac-tivities, such as antioxidant, anti-inflammatory, antibacterial, and insecticidal properties, and they exhibit insect growth inhibitory effects. Demethoxycurcumin and bisdemethoxycurcumin, two curcuminoids from the turmeric plant Curcuma longa L. inhibit the formation of a metho-prene-tolerant (Met)–Taiman (Tai) heterodimer complex as shown through in vitro yeast two-hybrid assays. An artificial diet containing 1% (w/v) demethoxycurcumin or bisdemethox-ycurcumin reduced the number of larvae, leading to no pupal development. Building on our re-sults regarding curcuminoids, researchers can use our study as a reference to develop eco-friendly pesticides.

In the majority of children with growth hormone (GH) deficiency (GHD), normal GH secretion may occur before the attainment of final height. The aim of the study was to assess the incidence of persistent and transient GHD and the effectiveness of recombined human GH (rhGH) therapy in children with isolated idiopathic GHD, with respect to the moment of therapy withdrawal and according to different diagnostic criteria of GHD. Analysis included 260 patients (173 boys, 87 girls) with isolated idiopathic GHD who completed rhGH therapy and have reassessed GH and IGF-1 secretion. The incidence of transient GHD with respect to different pre- and post-treatment criteria was compared together with assessment of GH therapy effectiveness. Incidence of transient GHD, even with respect to pediatric criteria was very high. Normal GH secretion occurred before the attainment of near-final height. Application of more restricted criteria decreased the number of children diagnosed with GHD but not the incidence of transient GHD among them. Poor response to GH therapy was observed mainly in patients with normal IGF-1 before treatment, suggesting that diagnosis of GHD may be false positive. Further efforts should be made to avoid overdiagnosis GHD and overtreatment of the patients.

The monocarboxylate transporters 8 (MCT8) and 10 (MCT10) are important for thyroid hormone (TH) uptake and signaling. Reduced TH activity is associated with impaired development, weight gain and discomfort. We hypothesized that autoantibodies (aAb) to MCT8 or MCT10 are prevalent in thyroid disease and obesity. Analytical tests for MCT8-aAb and MCT10-aAb were developed and characterized with commercial antiserum. Serum samples from healthy controls, thyroid patients and young overweight subjects were analyzed, and prevalence of the aAb was compared. MCT8-aAb were additionally tested for biological effects on thyroid hormone uptake in cell culture. Positive MCT8-aAb and MCT10-aAb were detected in all three clinical cohorts analyzed. MCT8-aAb were most prevalent in thyroid patients (11.9%) as compared to healthy controls (3.8%) and overweight adolescents (4.2%). MCT8-aAb positive serum reduced T4 uptake in cell culture in comparison to MCT8-aAb negative control serum. Prevalence of MCT10-aAb was highest in the group of thyroid patients as compared to healthy subjects or overweight adolescents (9.0% versus 4.5% and 6.3%, respectively). We conclude that MCT8 and MCT10 represent autoantigens in humans, and that MCT8-aAb may interfere with regular TH uptake and signaling. The increased prevalence of MCT8-aAb and MCT10-aAb in thyroid disease suggests that their presence may be of pathophysiological relevance. This hypothesis deserves an analysis in large prospective studies.

Pecan (Carya illinoinensis), as a popular nut tree, is widely planted in China in recent years. Grafting is an important technique for its cultivation. For a successful grafting, graft union development generally involves the formation of callus and vascular bundles at the graft union. To explore the molecular mechanism of graft union development, we applied high through-put RNA sequencing to investigate transcriptomic profiles of graft union at four time points (0d, 8d, 15d, and 30d) during pecan grafting process. We identified a total of 12,180 differentially expressed genes. In addition, we found that the content of auxin, cytokinin and gibberellin were accumulated at the graft unions during the grafting process. Correspondingly, genes involved in those hormone signaling were found to be differentially expressed. Interestingly, we found that most genes associated with cell division were up-regulated at callus formative stages, while genes related to cell elongation, secondary cell wall deposition, and programmed cell death were generally up-regulated at vascular bundle formative stages. In the meantime, genes responsible for reactive oxygen species were highly up-regulated across the graft union developmental process. These results will aid in our understanding of successful grafting in the future.

The nuclear hormone family of receptors regulates gene expression. The androgen receptor (AR) shuttles upon ligand binding and homodimerization from the cytosol into the nucleus to activate gene expression. Thyroid hormone receptors(TR), retinoic acid receptors (RAR), and the vitamin D receptor (VDR) are present in the nucleus bound to chromatin as a heterodimer with the retinoid X receptors (RXR) and repress gene expression. Ligand binding leads to transcription activation. The hormonal ligands for these receptors play crucial roles to ensure the proper conduct of very many tissues and exert effects on prostate cancer (PCa) cells. Androgens support PCa proliferation and deprivation alone or with chemotherapy is the standard therapy for PCa. RAR activation and 3,5,3'-triiodo-L-thyronine (T3) stimulation of TR support the growth of PCa cells. Ligand stimulation of VDR drives growth arrest, differentiation, and apoptosis of PCa cells. Often these receptors are explored as separate avenues to find treatments for PCa and other cancers. However, there is accumulating evidence to support receptor interactions and crosstalk of regulatory events whereby a better understanding might lead to new combinatorial treatments.

The essence of cross-modal generation and retrieval modeling for image-text interactions lies in semantic consistency. Among these, cross-modal representation alignment serves as the foundational requirement for achieving cross-modal semantic consistency. The crux of our proposed method entails the collaborative training of an image captioning model(referred to as the ’captioner’) and a pair of contrastive encoders for image-text matching(referred to as the ’concoder’). This synergistic approach yields concurrent enhancements in concoder’s performance, captioner’s proficiency, and cross-modal semantic coherence. We coin the proposed method as ‘ReCap’. To begin, we initialize the concoder through knowledge distillation from a pre-trained model. During the training process, we use the output of the initialized concoder as input to a residual attention network, jointly training it with the captioner to achieve semantic consistency. Subsequently, we iteratively update the concoder during the image-text momentum encoding phase using the residual attention network, creating a closed-loop for semantic consistency resolution. Upon completion of training, the concoder and captioner modules can be used independently to perform tasks related to cross-modal retrieval and cross-modal generation of text and images. In order to substantiate the efficacy of our proposed method, we initially conducted empirical experiments encompassing image-text retrieval and image captioning tasks, employing a widely recognized benchmark dataset, MSCOCO. Subsequently, we assessed the fine-grained cross-modal alignment performance of the concoder through an image classification task on the iNaturalist 2018 dataset. The achieved performance metrics notably surpassed those achieved by several incumbent state-of-the-art models, thus validating the proficiency of our method. Finally, motivated by the practical requirements of handling the nature conservation image data, we performed caption annotation for the iNaturalist 2018 dataset. Subsequently, we trained the ReCap on this annotated data. Experimental results demonstrate that our proposed method can maintain semantic consistency between cross-modal retrieval and image caption generation for species with similar visual features but distinct semantics. This achievement signifies a meaningful exploration in the field of cross-modal semantic consistency representation, holding significant practical value in the domain of biological research.

Cross-linked polyethylene (XLPE) is a highly all-important material renowned for its exceptional physical and chemical properties, and it is extensively utilized in various industries such as con-struction, piping, cable insulation and medical equipment. The cross-linking process of polyethylene involves chemical or physical bonding of polymer chains to enhance its resistance to heat, chemicals and mechanical stress. This study offers a comprehensive overview of recent research and potential advancements in this field, with a particular focus on the development of efficient techniques and environmentally sustainable cross-linking systems. It evaluates the opportunities and challenges faced by cross-linked polyethylene materials across diverse applications, providing valuable insights for future research in this area.

The circadian clock is a 24-hour cycle within the body that regulates various factors, including sleep, body temperature, and hormone secretion. It allows the body to adjust to the light and dark cycle. Disruptions to the circadian rhythm are important risk factors for many diseases, including neurodegenerative illnesses. The central clock is controlled by the clock genes in the suprachiasmatic nucleus (SCN) of the brain, and one of the main functions of the circadian clock is to regulate lipid metabolism. There has been a lack of investigation on the circadian regulation of lipid metabolism-related apolipoprotein genes in the brain; thus, this study sought to summarize the rhythmic expression of clock genes and lipid metabolism-related apolipoprotein genes within the SCN of Mus musculus. Out of the 20 apolipoprotein genes that were studied by the published database, all 9 genes were highly expressed in the SCN. Most of the 6 genes showed rhythmic expression in the brain of mice, suggesting that the master clock might regulate them. The results, therefore, reveal a potential target for preventing and treating circadian disorders. We summarized most studies of lipid-related apolipoprotein genes within limited locations of the SCN and brain to further understand how disordered cerebral lipid metabolism causes multiple brain diseases and disorders. We reviewed recent studies, determined the unexplored questions, and identified a potential direction for further research.

Enterocytozoon hepatopenaei (EHP) is an obligate intracellular parasite classified as a fungal pathogen, which causes hepatopancreatic microsporidiosis (HPM) in shrimp, resulting in large economic losses to the shrimp culture industry. However, the molecular mechanisms of how EHP affects hormonal regulation in shrimp were rarely reported. Thus, in the present study, we investigated the transcriptomic data of the hepatopancreas of EHP-infected and uninfected shrimp to study the hormonal regulation corresponding to EHP infection. The results showed that there were 157 differentially expressed genes (DEGs) at the hormonal regulatory level, of which 32 genes were upregulated and 125 genes were downregulated. Functional enrichment analysis showed that many DEGs were enriched in ecdysis-related pathways, including EGFR tyrosine kinase inhibitor resistance, thyroid hormone signaling pathway, and steroid hormone biosynthesis. Ten genes were randomly selected for qRT-PCR to verify the transcriptome sequencing results, and the results demonstrated that the expression of these genes were consistent with the results of the transcriptome. Our study provides an important dataset that contributes to further understanding of how EHP affects shrimp at the level of hormonal regulation. It provides a basis for further research and control of HPM.

Leucokinins (LKs) constitute a neuropeptide family first discovered in a cockroach and later identified in numerous insects and several other invertebrates. The LK receptors are only distantly related to other known receptors. Among insects, there are many examples of species where genes encoding LKs and their receptors are absent. Furthermore, genomics has revealed that LK signaling is lacking in several of the invertebrate phyla and in vertebrates. In insects, the number and complexity of LK expressing neurons vary, from the simple pattern in the larva of Drosophila where the entire CNS has 20 neurons of three main types, to cockroaches with about 250 of many different types. Common to all studied insects is the presence or 1-3 pairs of LK-expressing neurosecretory cells in each abdominal neuromere of the ventral nerve cord, that, at least in some insects, regulate secretion in Malpighian tubules. This review summarizes the diverse functional roles of LK signaling in insects, as well as other arthropods and mollusks. These functions include regulation of ion and water homeostasis, feeding, sleep-metabolism interactions, state-dependent memory formation, as well as modulation of gustatory sensitivity and nociception. Other functions are implied by the neuronal distribution of LK, but remain to be investigated.

The use of recombinant bovine somatotropin (rbST) leads to an increase, in variable amounts, of milk production in buffalo, but there is a lack of information on the influence of rbST on their metabolism. This study looked at the effects of a single 500 mg dose of rbST on lipid profile, liver and kidney function and physical, chemical and cellular constitution of milk in 14 buffalo over 14 days, from the 100th day of lactation, and compared them with 14 animals in a control group. From the 1st day after rbST, there was a rise in beta hydroxybutyrate (β-HBO), possibly due to the higher dry matter intake or by biotransformation of NEFA into β-HBO. Treatment did not influence blood glucose, non-esterified fatty acids (NEFA), triglycerides, cholesterol, total protein, albumin, AST, GGT, bilirubin, urea or creatinine. In 71.3% of the buffalo there was a gradual increase in milk production with maximal response in the first week that was then followed by a gradual decrease, whilst in 21.4%, the increase in production occurred between 7 and 10 days, and only 7.1% of animals did not respond. On the 3rd, 5th, 7th and 10th days after treatment, an increase was found in milk production between the two groups equal to 1.04, 1.52, 1.42 and 1.06 liters, respectively. In relative terms this means an increase in milk production, respectively, of 15.1%; 21.0%; 19.8 % and 15.1 %. The constitution of the milk showed no difference in the amounts of fat, lactose, total solids or somatic cell count; however, on the 3rd day after rbST, there was a decrease in protein; notably, from the 5th day, protein values show no statistical difference. It can be concluded that the application of rbST in buffalo from the 100th day of lactation is metabolically safe, since the treatment neither caused imbalances in fat metabolism nor overloaded the liver or renal function, and the changes in milk composition were transient and limited to a decrease in milk protein.

Parabens are classified as endocrine disrupting compounds (EDCs), capable of interfering with the normal functioning of the thyroid, affecting the proper regulation of the biosynthesis of thyroid hormones (TH) which is controlled by hypothalamic-pituitary-thyroid axis (HPT). Given the crucial role of these hormones in health and the growing evidence of diseases related to thyroid dysfunction, this review looks at the effects of paraben exposure on the thyroid. In this study, we considered research carried out in vitro, in vivo, and epidemiological studies published between 1951 and 2023, which demonstrated an association between exposure to parabens and dysfunctions of the HPT axis. In humans, exposure to parabens appears to increase thyroid-stimulating hormone (TSH) levels, while in rodents, exposure decreases TSH levels. The effects on HT levels are also poorly described, as well as peripheral metabolism. Regardless, recent studies have shown different actions between different subtypes of parabens on the HPT axis, which allows us to speculate that the mechanism of action of these parabens is different. Furthermore, studies of exposure to parabens are more evident in women than in men. Therefore, future studies are needed to clarify the effects of exposure to parabens and their mechanisms of action on this axis.

The corpus luteum is a temporary reproductive endocrine structure established from a ruptured follicle wall after ovulation. In the ovarian cycle of ruminant species, the corpus luteum organ undergoes a repeated pattern of specific cellular proliferation, differentiation, and transformation. The corpus luteum encounters several physiological events, including growth, function, and regression throughout its life span. Also, the corpus luteum comprises granulosa and theca cells and endothelial cells, such as luteal steroidogenic cells and luteal endothelial cells. These cells play an important role in the physiology of the corpus luteum and the maintenance and degeneration of the corpus luteum. Furthermore, the role of reproductive hormones in the ovaries is important. Representative hormones include estrogen, progesterone, prostaglandin F2α, and oxytocin. Understanding their functions is important in studying the physiological phenomena and various mechanisms of the corpus luteum in the ovary. Therefore, the following review will discuss the role of reproductive hormones and luteal cell types in the microenvironment of the corpus luteum in the bovine ovary.

A rapid and appropriate genetic and metabolic acclimation, which is crucial for plants’ survival in a changing environment, is maintained due to the coordinated action of plant hormones and cellular degradation mechanisms influencing proteostasis. The plant hormone abscisic acid (ABA) rapidly accumulates in plants in response to environmental stress and plays a pivotal role in the reaction to various stimuli. Increasing evidence demonstrates a significant role of autophagy in controlling ABA signaling. This field has been extensively investigated and new discoveries are constantly being provided. We present updated information on the components of the ABA signaling pathway, particularly on transcription factors modified by different E3 ligases. Then, we focus on the role of selective autophagy in ABA pathway control and review novel evidence on the involvement of autophagy in different parts of the ABA signaling pathway that are important for crosstalk with other hormones, particularly cytokinins and brassinosteroids.

Newcastle disease virus (NDV) causes a highly contagious and devastating disease in poultry, Newcastle disease (ND). ND causes heavy economic losses to the global poultry industry by decreasing the growth rate, decrease egg productions, mortality, and morbidity. Although, significant advances have been made in the vaccine development, but outbreaks are reported in vaccinated birds leading to overall decreased growth rate. In this study, we report the damage caused by the NDV infection in the pancreatic tissues of vaccinated as well as specific pathogen free chickens. The histopathological examination of the pancreas showed sever damage in the form of partial depletion of zymogen granules, acinar cell vacuolization, necrosis, and apoptosis, congestion in the large and small vessels, sloughing of epithelial cells of pancreatic duct, and mild perivascular edema. Increased plasma levels of corticosterone, somatostatin, were observed in NDV infected chicks at 3 and 5-day post infection (DPI). Slight decrease in the plasma concentrations of the insulin were noticed at 5 DPI. Significant changes were not observed in the plasma levels of glucagon. Furthermore, NDV infection has decreases the activity and mRNA expression of amylase, lipase, and trypsin from the pancreas. Taken together, our findings highlight that NDV induces extensive tissue damage in pancreas, decrease the activity and expression of pancreatic enzymes and increase plasma corticosterone and somatostatin.

This study checked whether vitamin D (Vit-D) supplementation improves the efficacy of resistance training (RT) in terms of increasing muscle strength and lean body mass (LBM) and influencing cardiorespiratory fitness (VO2max) in Vit-D insufficient middle-aged healthy men. Participants (n = 28) were quasi‐randomly assigned to one of the two groups, which, in a double‐blind manner, supplemented their diet daily with either Vit‐D (8000 IU; VD) or placebo (PLC) during participation in a 12‐week supervised RT program. During the intervention, serum Vit‐D concentrations increased 2.6‐fold (p < 0.001) in the VD group, while no changes occurred in the PLC group. Muscle strength gains (p < 0.001) as measured in seven exercises performed on RT equipment and increases (p < 0.001) in LBM were similar in the two groups. Total fat mass, percent total fat, and percent android fat decreased (p < 0.05) to a similar extent in both groups, but there was no change in VO2max in either group. In conclusion, in healthy Vit‐D insufficient middle-aged men engaged in resistance training, Vit‐D supplementation increases serum 25(OH)D levels but does not enhance gains in muscle strength and LBM or decreases in fat mass and fat percentage and does not affect cardiorespiratory fitness.

Background/Objectives: An age-associated increase in serum levels of sex hormone binding globulin (SHBG) is considered to be one of the factors leading to the development of male hy-pogonadism. Aim of the study: to study the relationship between the concentration of sex hor-mone-binding globulin in the blood serum and the age of the man, the level of total and free testosterone. A single-center retrospective cross-sectional study was conducted. The results of laboratory tests of 162 male patients aged from 18 to 56 years (median - 34 years) were analyzed. Methods: The level of total testosterone and sex hormone binding globulin (SHBG) was deter-mined by chemiluminescent immunoassay. The level of free testosterone was determined by the calculation method according to Vermeullen. Statistical analysis was performed using SPSS Sta-tistics v23. Results: Correlation analysis did not reveal a significant relationship between age and SHBG levels, as well as between age and total testosterone levels. Serum SHBG concentration showed a significant (p

Melatonin, a naturally occurring chemical, has pleiotropic effects across various species. It plays a vital role in animals by regulating the body clock, while in plants, it is known to resist aging. Melatonin is associated with various plant physiological processes, including stress response, plant growth, and flowering time. It has prospects in enhancing and promoting plant growth and development, as well as in strengthening crop yield and increasing sustainability in agriculture. This review summarized the potential roles of melatonin in several plant species, as well as its biosynthetic modes. In addition, we described the recently uncovered melatonin features in plants, summarized the issues and challenges facing plant melatonin research and some feasible solution ideas are proposed.

This retrospective study aimed to evaluate the performance of the hormone treatment protocols, determine the factors associated with pregnancy success after hormone treatment, and compare the cost-efficiencies of two types of hormone treatment among cyclic and noncyclic anestrous dairy cows. The clinical records of 279 anestrous cows who received hormone treatment for artificial insemination (AI) from 64 herds in the western region of Thailand were obtained from Kasetsart University Veterinary Teaching Hospital from January to August 2017. The performance of the hormone treatment protocols, fixed-time AI (TAI) and estrus detection before AI (EAI), showed that the pregnancy risk for the TAI protocol was higher than for the EAI protocol, but pregnancy per AI did not differ significantly between the two protocols in cyclic and noncyclic cows. Multivariate logistic regression analysis showed that cows receiving the TAI protocol were more likely to be pregnant compared to those treated with the EAI protocol. Cows with a 3.00 body condition score (BCS) &lt;3.75 after treatment and loose-housing cows were more likely to become pregnant. Treatment during winter showed higher pregnancy success than in the summer and rainy seasons. The cost-efficiency analysis showed that the TAI protocol was the most cost-efficient option for noncyclic cows, whereas the EAI protocol was the most cost-efficient option for cyclic cows.

The global population is at risk of vitamin D deficiency due to low exposure to sunlight and low intake of the vitamin through diet. The aim was to investigate in women the association between vitamin D status and parathyroid hormone (PTH), ultraviolet radiation, lifestyle, ethnicity, social conditions, and residential greenness. A 1-year longitudinal study assessed vitamin D status in 309 women, latitude 51° 14' N. Blood samples were taken four times throughout the year for analysis of 25(OH)D and serum PTH concentration. After each seasonal visit, the individuals completed 4-day diet diaries and used two dosimeter badges for 1 week to estimate weekly UVR exposure. A questionnaire was applied to provide information about lifestyle and their ethnicity. Residential greenness was measured by Normalized Difference Vegetation Index (NDVI), within a 1000 m radius around each participant’s home address. Women living in greener spaces were more likely to have improved vitamin D status (RR: 1.51; 95%CI: 1.13 – 2.02), as well as those who were more exposed to UVR (RR: 2.05; 95%CI: 1.44 – 2.92). Our results provided a first insight into the connection between vitamin D, residential greenness, and lifestyle in a region of temperate climate and with a high degree of urbanization.

Studies report variable effects of sex hormones on serious diseases. Severe disease and mortality rates in COVID-19 show marked gender differences that may be related to sex hormones. Sex hormones regulate the expression of the viral receptors ACE2 and TMPRSS2, which affect the extent of viral infection and consequently cause variable outcomes. In addition, sex hormones have complex regulatory mechanisms that affect the immune response to viruses. These hormones also affect metabolism through obesity, and severe disease can result from complications such as thrombosis. This review presents the latest research on the regulatory functions of hormones in viral receptors, immune responses, complications as well as their role in COVID-19 progression. It also discusses the therapeutical possibilities of these hormones by reviewing the recent findings of clinical and assay studies.

In insects, Adipokinetic hormone is the primary hormone responsible for the mobilization of stored energy. While a growing body of evidence has solidified role of Adipokinetic hormone (AKH) in modulating the physiological and behavioral responses to metabolic stress, little is known about the upstream endocrine circuit that directly regulates AKH release. We evaluated the AKH-producing cell (APC) transcriptome to identify potential regulatory elements controlling APC activity, and found that a number of receptors show consistent expression levels, including all known dopamine receptors and the Pigment Dispersing Factor receptor (PDFR). We tested the consequences of targeted genetic knockdown and found that AKH expression of RNAi elements corresponding to each dopamine receptor caused a significant reduction in survival under starvation. In contrast, PDFR knockdown significantly extended lifespan under starvation whereas expression of a tethered PDF in APCs resulted in a significantly shorter lifespan. These manipulations caused various changes in locomotor activity under starvation. We used live-cell imaging to evaluate the acute effects of the ligands for these receptors on APC activation. Dopamine application led to a transient increase in intracellular calcium in a sugar-dependent manner. Furthermore, co-application of dopamine and ecdysone led to a complete loss of this response, suggesting that these two hormones act antagonistically. We also found that PDF application led to an increase in cAMP in APCs, and that this response was dependent on expression of the PDFR in APCs. Together these results suggest a complex circuit in which multiple hormones act on APCs to modulate metabolic state.

Phenotypic plasticity in response to adverse conditions determines plant productivity and survival. The aim of this study was to test if two highly productive Populus genotypes, characterized by different in vitro etiolation patterns, differ also in their responses to hormones gibberellin (GA) and abscisic acid (ABA), and to a GA biosynthesis inhibitor paclobutrazol (PBZ). The experiments on shoot cultures of ‘Hybrida 275’ (abbr. H275; Populus maximowiczii × P. trichocarpa) and IBL 91/78 (Populus tremula × P. alba) were conducted either by modulating the physical in vitro environment or by adding specific chemicals to the nutrient medium. Our results show that there are significant differences between the studied genotypes in environmental and hormonal regulation of growth responses. The genotype H275, which responded to darkness with PBZ-inhibitable shoot elongation, was unable to recover its growth after treatment with ABA. In contrast, the genotype IBL 91/78, whose shoot elongation was not affected either by darkness or PBZ treatment, recovered so well after the ABA treatment that, when rooted subsequently, it developed longer shoots and roots than without ABA treatment. Our results indicate that GA catabolism and repressive signaling provide an important pathway to control growth and physiological adaptation in response to immediate or impending adverse conditions. These observations can help breeders define robust criteria for identifying genotypes with high resistance and productivity and highlight where genotypes exhibit susceptibility to stress.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

Little is known about the association between equol and bioavailable testosterone (BT) in adults. We examined the associations of urinary equol concentrations with serum total, bioavailable and free testosterone (FT), dehydroepiandrosterone sulfide (DHEAS), free androgen index (FAI) and sex hormone-binding globulin (SHBG) concentrations. This cross-sectional study included 1904 women aged 59.7 years. Urinary equol and serum sex hormone concentrations were measured. Overall, urinary equol tended to be inversely associated with bioactive forms of androgenic indices (BT, FT or FAI) but not with total testosterone (TT) or DHEAS. Urinary equol was also positively associated with SHBG. In multi-covariate-adjusted analyses stratified by menopausal status, graded and inverse associations between urinary equol and bioactive forms of androgenic indices (BT, FT and FAI) were observed in postmenopausal women (all p-trends <0.05), but not in premenopausal women. A significant positive association between urinary equol and SHBG was observed only in postmenopausal women. No significant associations were observed between urinary equol and TT or DHEAS in either group. A path analysis indicated that these associations of equol with androgens in postmenopausal women might be mediated by SHBG. Our findings indicated urinary equol exhibited graded and inverse associations with BT or FT but not TT in women.

1) Background: The Aicardi-Goutières syndrome (AGS) is a rare congenital disease which courses with severe psychomotor delay in neurodevelopment. We studied a 3-years and 4-months old child with very important growth and weight affectation, microcephaly and loss of his developmental skills from 16-months of age, in which previous metabolic and genetic studies discarded any abnormality. Therefore diagnosis was cerebral palsy of unknown etiology. He presented spastic paraparesia, poor fine motricity, cognitive impairment and absence of oral communication. One year after discharge, a de novo mutation was detected in a single nucleotide in the gene IFIH1: c.2317G>C, being then diagnosed of AGS. 2) Methods: Blood analysis showed very low IGF-1 and slightly elevated liver transaminases. Treatment consisted in GH (0.04 mg/kg/day), melatonin (20 mg/day, and after 3-months 50 mg/day), and daily intense neurorehabilitation (5 days/week). Tests for evaluating childhood developmental milestones (GMFM-88, BDIST and the WeeFim test) were carried out every 3-months. 3) Results: The equivalent age at admission (10-months) increased to 24-months at discharge. There were clear improvements in spasticity, fine motor function, swallowing, cognition and autonomy as well as in communication, growth and weight. 4) Conclusion: Most likely melatonin blocked or decreased the interferon signature, allowing GH and neurorehabiltation to act on neurodevelopment.

In this work, two plasmonic structures with two different periodic nanostructures (nanodisk and nanostrip arrays) separated from the gold layer by an ultrathin dielectric Al2O3 layer are proposed, and their optical properties are simulated as 3-dimensional models using COMSOL Multiphysics software tool. The optical responses, such as the amplification of the electric field and the scattering, absorption and extinction cross sections of the two structures, are investigated and compared. The results show that both structures show strong field enhancement in their gap layer, and the structure with the periodic array of metal nanodisks shows stronger field enhancement and larger absorption, extinction, and scattering cross sections in its dipole resonance wavelength, which is defined as a bright plasmonic mode. In addition, some weaker resonant modes are observed for both structures and the reason for their generation is dis-cussed. The analysis of different possible modes in such structures is crucial for their application in various fields.

Background/Objectives: Women with subclinical hypothyroidism (SCH) were reported to be at an increased perinatal risk. We aimed to investigate the relationship between SCH and perinatal outcomes in singleton pregnancies resulting from assisted reproduction technology (ART). Methods: We retrospectively examined the perinatal outcomes of ART singleton pregnancies in women who underwent thyroid function screening before conception and delivered at our hospital from January 2020 to July 2023. We defined SCH as thyroid-stimulating hormone (TSH) levels <2.5 mU/L and normal free T₄ levels. The patients were divided into three groups: normal thyroid function (group A), SCH without levothyroxine therapy (group B), and SCH with levothyroxine therapy (group C). The risks of preterm birth, preeclampsia, fetal growth restriction, manual placental removal, and blood loss at delivery were compared among the three groups. Results: Out of the 650 ART singleton deliveries, 581 were placed in group A, 34 in group B, and 35 in group C. The preterm birth rate at <34 weeks was significantly higher in group B and significantly lower in group C than in group A. The rate of preterm delivery at <34 weeks increased in correlation with TSH levels. Levothyroxine therapy was the significant preventive factor for preterm birth at <34 weeks. Conclusions: The preterm birth rate before 34 weeks was significantly higher in the SCH group. Levothyroxine therapy is a significant protective factor against preterm birth before 34 weeks. Universal screening for thyroid function and appropriate hormone therapy in pregnant women may help reduce perinatal risks, including preterm birth.

The glycoprotein hormones luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone and chorionic gonadotropin consist of a common alpha-subunit and a hormone-specific beta-subunit. The alpha-subunit is expressed in thyrotrophs, gonadotrophs, and placental cells, and its expression is regulated by extracellular signal molecules. Here, we assessed the regulation of the gene encoding the alpha-subunit in placental JEG-3 cells, using a chromatin-embedded reporter gene under the control of the glycoprotein hormone alpha-subunit promoter. The results show that stimulation of the cells with forskolin, an activator of adenylate cyclase, induced transcription of a reporter gene controlled by the alpha-subunit promoter. Similarly, expression of a nuclear-targeted catalytic subunit of cAMP-dependent protein kinase increased reporter gene transcription. Expression experiments involving constitutively active mutants of MKK6 and MEKK-1 showed that the alpha-subunit promoter is responsive to activation of p38 protein kinase but only slightly responsive to activation of c-Jun N-terminal protein kinase. Finally, we show that stimulation of a Galphaq-coupled designer receptor triggers transcription of a reporter gene controlled by the glycoprotein hormone alpha-subunit promoter, mediated by the transcription factor CREB. Deletion mutagenesis highlights the importance of a tandem cAMP response element within the alpha-subunit promoter that acts as a point of convergence for different signaling pathways.

PIEZO1 plays a crucial role in the human body as a mechanosensory ion channel. It has been demonstrated that PIEZO1 is important in tissue development and regulating many essential physiological processes. Studies have suggested that the PIEZO1 ion channel plays a role in invasion and progression in cancer; elevated levels of PIEZO1 have been correlated with increased migration in breast cancer cells, chemo-resistance and invasion in gastric cancer cells, and increased invasion of osteosarcoma cells. In addition, high PIEZO1 expression levels were correlated with a worse prognosis in glioma patients. On the other hand, studies in lung cancer have attributed high PIEZO1 levels to better patient outcomes. However, the clinical impact of PIEZO1 in breast cancer is not well characterized. Therefore, our goal was to determine the clinical relevance of PIEZO1 in breast cancer. Analysis of breast cancer data from The Cancer Genome Atlas (TCGA) was conducted to investigate PIEZO1 expression levels and correlation to survival, followed by validation in an independent dataset, GSE3494. We also performed gene set enrichment analysis (GSEA) and analyzed immune cell levels in breast tumors from TCGA through a CIBERSORT algorithm. Our results demonstrated that PIEZO1 expression levels are higher in hormone receptor (HR) negative than HR positive cohorts. High PIEZO1 expression is correlated with a significant decrease in survival in HR negative cohorts, suggesting that PIEZO1 could be utilized as a prognostic biomarker in HR negative breast cancer. GSEA showed that various signaling pathways associated with more invasive phenotypes and resistance to treatments, including epithelial-mesenchymal transition (EMT), hypoxia, and multiple signaling pathways, are enriched in high PIEZO1 HR negative tumors. Our results also demonstrated a decrease in CD8+ and CD4+ T cell infiltration in high PIEZO1 HR negative tumors. Further investigations are necessary to elucidate the mechanistic roles of PIEZO1 in HR negative breast cancer.

Abiotic stress is an adverse environmental factor that severely affects plant growth and development, and plants have developed complex regulatory mechanisms to adapt to these unfavourable conditions through long-term evolution. In recent years, many transcription factor families of genes have been identified to regulate the ability of plants to respond to abiotic stresses. Among them, AP2/ERF (APETALA2/ethylene responsive factor) family is a large class of plant-specific that regulate plant response to abiotic stresses and can also play a role in regulating plant growth and development. This paper reviews the structural features and classification of AP2/ERF transcription factors, that transcriptional regulation, reciprocal proteins, downstream genes and hormone-dependent signalling and hormone-independent signalling pathways are involved in the response to abiotic stress. The study of AP2/ERF transcription factors and interacting proteins, as well as the identification of their downstream target genes, can provide us with a more comprehensive understanding of the mechanism of plant action in response to abiotic stress, which can improve the tolerance ability of plants in abiotic stress, and provide more theoretical basis for rice to obtain more yields under abiotic stress.

The discovery of microRNAs (miRNAs) has fundamentally transformed our understanding of gene regulation. The competing endogenous RNA (ceRNA) hypothesis postulates that not only messenger RNAs but also other RNA transcripts, such as long non-coding RNAs and pseudogenes, can act as natural miRNA sponges. These RNAs influence each other’s expression levels by competing for the same pool of miRNAs through miRNA response elements on their target transcripts, thereby modulating gene expression and protein activity. In recent years, these ceRNA regulatory networks have gained considerable attention in cancer research. Several studies have identified cancer-specific ceRNA networks. Nevertheless, prior bioinformatic analyses have focused on long non-coding RNAs-associated ceRNA networks. Here, we identify an extended-ceRNA network (including both long non-coding RNAs and pseudogenes) shared across a group of four hormone-dependent (HD) cancers, i.e., prostate, breast, colorectal, and endometrial cancers, using data from The Cancer Genome Atlas (TCGA). We performed a functional enrichment analysis for differentially expressed genes in the shared ceRNA network of HD cancers, followed by a survival analysis to determine their prognostic ability. We identified two long non-coding RNAs, nine genes, and seventy-four miRNAs in the shared ceRNA network across four HD cancers. Among them, two genes and forty-one miRNAs were associated with at least one HD cancer survival. This study is the first to investigate pseudogene associated ceRNAs across a group of related cancers and highlights the value of this approach to understanding shared molecular pathogenesis in a group of related diseases.

The Pygmy hog (Porcula Salvania), till recently, classified as a critically endangered suid, is facing the threat of extinction globally due to habitat degradation. Efforts are being made to protect the pygmy hogs from extinction and breed them in captivity under Pygmy Hog Conservation Pro-gramme (PHCP). However, very little information is available on the reproductive physiology of pygmy hogs. Therefore, the present study aimed to standardize enzyme immunoassays (EIAs) for monitoring pregnancy and reproductive status using progesterone and testosterone metabolites. A total of 785 faecal samples were collected from five females and two males over a period of one year from PHCP Research and Breeding Centre, Guwahati, Assam. High-pressure liquid chro-matography (HPLC) analysis revealed the presence of immunoreactive progesterone and testos-terone metabolites in faeces. Mating was observed in all the five females and four of them gave birth successfully. We were able to detect pregnancy using faecal progesterone metabolites. Based on mating and parturition, the mean gestation period was estimated to be 153.25 days from four females. The breeding centre recorded 172 births between 1996 and 2000 and found strong sea-sonality in births and most of the births were between May and June. Faecal testosterone metabo-lites were significantly higher in the breeding season than the non-breeding season. This is the first study and will help in future breeding programs in other captive breeding centres and reproduc-tive monitoring of reintroduced populations.

Cellular communications play pivotal roles in multi-cellular species, but they do so also in uni-cellular species. Moreover, cells communicate with each other not only within the same individual but also with cells in other individuals belonging to the same or other species. These communications occur between two unicellular species, two multicellular species, or between unicellular and multicellular species. The molecular mechanisms involved exhibit diversity and specificity, but they share common basic features which allow common pathways of communication between different, and sometimes very different species. These interactions have been made possible by the high degree of conservation of the basic molecular mechanisms of interaction of many ligand-receptor pairs in evolutionary remote species. These inter-species cellular communications played crucial roles during Evolution and must have been positively selected, particularly when collectively beneficial in hostile environments. We think that communications between cells did not arise after their emergence but was part of the very nature of first cells. Synchronization of populations of non-living protocells through chemical communications may have been a mandatory step towards their emergence as populations of living cells and explain the large commonality of cell communication mechanisms among microorganisms, plants, and animals.

Obesity in children is associated with vitamin D (VD) deficiency and cardiometabolic abnormalities. To analyze the effects of VD supplementation in adolescents with obesity enrolled in a weight-loss program. Adolescents with obesity (n=26) and with normal weight (n=23; controls) were matched for age, sex, and puberty stage. The obesity group followed a 3-month weight-loss program that combined a reduced caloric intake with interval training physical activity and during which they received or not VD supplementation (4000 IU/d) (n=13/group; random assignation). The anthropometric parameters (BMI z-score, fat mass); serum levels of 25(OH)D, calcium and parathyroid hormone (PTH), cardiometabolic factors (triglycerides, HDL, and LDL cholesterol), fasting glucose and insulin, and homeostasis model assessment of insulin resistance index; diastolic, systolic and mean blood pressure, and inflammatory status (C-reactive protein, CRP) were measured at baseline and at the end of the 3-month program. At baseline, 25(OH)D concentration was lower and VD insufficiency (25(OH)D levels <50 nmol/L) rate was higher (73% vs 22%) in the obesity than in the normal-weight group. All cardiometabolic factors were altered in the obesity compared with the normal-weight group. After the 3-month weight-loss program, 25(OH)D levels was >50 nmol in all adolescents with obesity, but only in 46% of normal-weight adolescents. Moreover, the weight-loss program improved the cardiometabolic factors, inflammatory status (CRP) and physical performance, but VD supplementation did not have any additional effect. Analysis only of the adolescents with obesity and VD deficiency (25(OH)D <50 nmol/L) at baseline showed a significant correlation between the change in PTH and CRP (p=0.02) in the supplemented obesity group, while the increase in 25(OH)D only tended to be correlated with CRP decrease. Vitamin D supplementation could reduce VD insufficiency in adolescent with obesity, but does not have any additional effect on cardiometabolic factors when combined with a weight-loss program.

The voluminous daily output of autism research has become increasingly disconnected, existing largely within highly specific subspecialty areas, and lacking cross-disciplinary linkages of context, theory, and findings to inform a unified body of knowledge. Robust syntheses of published research across the fields of psychiatry, cellular and molecular biology, neurology, endocrinology, immunology, behavioral and social sciences, and pedagogy may help clarify and extend current knowledge by guiding more efficient future research efforts investigating underlying causes, developmental divergences, novel treatments, and specific, sensitive biological markers in autism. This synthesis of interdisciplinary research indicates the hypothalamic-pituitary-adrenal (HPA) stress axis may be at the center of an interaction among sex steroids, immune function, signaling protein transcriptions, neurogenesis, and dysregulation of brain structures sending or receiving projections from the HPA stress axis. These interaction manifest observably as a range of sexually dimorphic behaviors and functional limitations often falling within the current diagnostic features of Autism Spectrum Disorder (ASD). The pathogenicity of endocrine dysregulation may serve as a valuable model for developing a cohesive theory of ASD by explaining how the HPA and connected brain areas respond to extreme conditions of dysregulated endocrine signaling to cause symptoms associated with autism.

Endocrine disruptor compounds are exogenous agents able to interfere with a gland function, exerting their action across different functional passages, from the synthesis to the metabolism and binding to receptors of the hormone produced. Several issues such as different levels and time of exposure and different action across different ages as well as gender, make the study of endocrine disruptors still a challenge. Thyroid is very sensitive to the action of disruptors, and considering the importance of a correct thyroid function for physical and cognitive functioning, addressing this topic should be considered a priority. In this review we examined the most recent studies, many of them concentrating on maternal and child exposure, conducted to assess the impact of industrial chemicals which showed an impact on thyroid function. So far, the number of studies conducted on that topic is not sufficient to provide solid conclusions and lead to homogeneous guidelines. The lack of uniformity is certainly due to differences in areas and populations examined, the different conditions of exposures and the remarkable inter-subject variability. Nonetheless, the European Commission for Health and Food Safety is implementing recommendations to ensure that substances identified as endocrine disruptors will be withdrawn from the market.

Lower cutoff levels in screening programs have led to an increase in the proportion of detected cases with transient hypothyroidism, leading to increase of the overall incidence of primary congenital hypothyroidism (CH) in several countries. We have performed retrospective evaluation on the data from 251,008 (96.72%) neonates screened for thyroid-stimulating hormone (TSH) level in dried blood spot specimens taken 48 hours after birth, between 2002 and 2015, using DELFIA method. A TSH value of 15 mIU/L was used as the cutoff point until 2010 and 10 mIU/L thereafter. Primary CH was detected in 127 newborns (1/1976) of which 81.1% had permanent and 18.9% had transient CH. The incidence of primary CH was increased from 1/2489 until to 2010 to 1/1585 thereafter (p=0.131). However, the incidence of permanent CH was slightly increased (p=0.922), while the transient CH incidence had 8-fold increasing after lowering the TSH cutoff level (p<0.001). In cases with permanent CH, we observed lower frequency for thyroid dysgenesis (82.7 vs. 66.7%) and higher frequency for normal in-situ thyroid gland (17.3 vs. 33.3%), for the period with reduced TSH cutoff value. Our findings support the impact of lower TSH cutoff on the increasing incidence of congenital hypothyroidism.

Cross-cultural mobility is a phenomenon that is increasingly growing, and the resulting stress has become a severe health issue. Thus, we conducted a systematic review of articles reporting research on stress measures of cross-cultural mobility or acculturative stress, emphasizing its internal structure. We adopted the PRISMA procedures for scoping reviews (e.g., searching articles in databases), resulting in the inclusion 20 articles in the final analysis that present evidence of validity based on the internal structure of 16 measures. The most common factors identified were related to cultural stressors, language stressors, and discrimination stressors. After analyzing a cross-cultural mobility stress concept implicit in the definitions used in the articles, we found that most measures of acculturative stress did not evaluate it according to the Stress and Coping Model of Lazarus and Folkman. Most measures only focused on part of the phenomena (some estimated the stressors, others the coping strategies). Few took into account the physiological and psychological responses to internal or external stressors, and even fewer considered its positive aspects (eustress). Consequently, it is pivotal to develop measures that take into account the multiple dimensions of the cross-cultural mobility stress. Other results (e.g., validity evidence of the measures) and limitations of this systematic scoping review are presented and discussed.

A separate group consists of compounds that are able to simultaneously interact with both orthosteric and allosteric sites, which are classified as bitopic GPCR ligands [74, 76-81]. They have two pharmacophores, one of which binds with high affinity to the orthosteric site, while the other, with lower affinity, binds to the allosteric site. If these sites are spatially separated in the receptor, then the pharmacophores in the bitopic ligand must be connected with a flexible linker, the length of which exactly corresponds to the distance between the orthosteric and allosteric sites. At the same time, it is important that the linker does not significantly affect the conformational rearrangements in the receptor caused by its activation by orthosteric and (or) allosteric agonists [74, 79].

Texture has long been considered an important attribute for food acceptance. However, which specific textural characteristics contribute to overall acceptance of a food is not well understood. It has been suggested that texture contrasts and combinations are a universal feature in giving foods a desirable texture, yet this notion is largely based upon anecdotal data. This study uses multiple survey research methods to assess the importance of texture contrast and combinations across cultures (Poland, U.S.A., and Singapore). Participants (n = 288) completed a survey that included overt measures of food texture contrast importance as well as free response questions regarding texture. The overall importance of texture for food liking was not different across the populations. However, the participants from Singapore and Poland gave more importance to a desirable food having multiple textures than the U.S.A. cohort. When looking at free responses, participants were twice as likely to mention combinations (multiple textures) with a texture contrast when describing foods they liked, in comparison to foods they disliked. This was observed across all 3 cultures. However, the type and quantity of texture terms used within combinations were different among cultures. For instance, Asians enjoyed more texturally diverse food combinations than the other two cultures. These findings highlight the importance of texture contrasts and combinations in three distinct cultures.

This paper presents a novel CNN-based architecture, referred to as Q-Net, to learn local feature descriptors that are useful for matching image patches from two different spectral bands. Given correctly matched and non-matching cross-spectral image pairs, a quadruplet network is trained to map input image patches to a common Euclidean space, regardless of the input spectral band. Our approach is inspired by the recent success of triplet networks in the visible spectrum, but adapted for cross-spectral scenarios, where for each matching pair there are always two possible non-matching patches; one for each spectrum. Experimental evaluations on a public cross-spectral VIS-NIR dataset shows that the proposed approach improves the state-of-the-art. Moreover, the proposed technique can also be used in mono-spectral settings, obtaining a similar performance to triplet network descriptors, but requiring less training data.

Chaotic theory is commonly being researched for application in image encryption scheme (IES). In this paper, a novel two-dimensional cross hyperchaotic Sine-modulation-Logistic map (2D-CHSLM) based on the famous Sine and Logistic maps. The hyperchaotic behaviors of 2D-CHSLM is testified with the help of their bifurcation diagrams, trajectory plots, Lyapunov exponents, sample entropy, C0 complexity, permutation entropy and 0-1 test. A new bit-level IES with traditional encryption structure is proposed utilizing 2D-CHSLM. The 2D-CHSLM-IES performs a 2D-CHSLM-based bit-level confusion using zig-zag transform and a 2D-CHSLM-based cross coupled diffusion operations for generating a highly secure cipher-image. Then the simulations and security analyses are further carried out with the help of key space, key sensitivity, histogram, correlation, information entropy, differential attack, noise and data loss attacks, prove that the security of the proposed 2D-CHSLM-IES

Polycystic Ovarian Syndrome (PCOS) is a common endocrine condition that affects 8–13% of women of reproductive age and is one of the leading causes of anovulation and infertility. In Kazakhstan, the prevalence of this syndrome is particularly high compared to other countries and the global average. Currently, the diagnosis of polycystic ovarian syndrome is based on internationally established Rotterdam criteria, using hyperandrogenism, i.e. high testosterone levels, as a key parameter. These criteria are applied to diagnose PCOS in all female patients, although obese patients may have excess testosterone produced by adipose tissue. To avoid possible false PCOS diagnoses, an additional criterion could be considered to diagnose PCOS among obese women. Anti-Müllerian hormone (AMH) is promising as a more effective diagnostic criterion, since its level represents the state of the ovarian reserve and adipose tissue does not produce AMH. Therefore, the use of AMH instead of hyperandrogenism as a diagnostic criterion for PCOS among obese women might improve diagnostic precision and patient treatment. In this study, data on the levels of various hormonal indicators such as estrogen, progesterone, and others were analyzed for a large cohort of female patients with and without PCOS to explore possible correlations between these indicators, AMH, and testosterone. The findings suggest that the absence of a negative correlation between AMH and follicle-stimulating hormone (FSH), and a positive correlation of AMH with testosterone could support the use of AMH as a reliable additional criterion for PCOS diagnosis among obese women.

Correlations among estrus cycle, pyometra, and canine diabetes mellitus (CDM) have been described since the late 1950s, and substantial progress in understanding mechanisms beyond was achieved nowadays. Progesterone-related diabetes mellitus (PRDM) in dogs is known for its particular potential for diabetes remission. Thus, a deep understanding of the physiopathological aspects involved is crucial to postulate treatment guidelines to improve the PRDM remission rate, as well as to inform preventive measures. This narrative review aims to provide relevant detailed information on 1) canine estrus cycle and its impact on CDM etiology and management, 2) the role of pyometra as a further cause of insulin resistance, and 3) useful individual therapeutic and preventive strategies. Pharmacological annulment of progesterone effects, as well as inflammatory and progesterone-related conditions resolution in association with adequate exogenous insulin therapy, and residual beta cell function, are key aspects to achieve remission, or at least to improve diabetic clinical control. In this way, spaying should be considered mandatory in most PRDM cases. Preventive measures against CDM can include spaying recommendations; however, individual-based recommendations should be considered since castration may be associated with some long-term health issues.

Repurposing previously approved drugs may fast track the route to clinic for potential senotherapeutics and improves the inefficiency of the clinical drug development pipeline. We carried out a repurposing screen of 240 clinically approved molecules in human primary dermal fibroblasts for effects on CDKN2A expression. Molecules demonstrating effects on CDKN2A expression underwent secondary screening for senescence-associated beta galactosidase (SAB) activity, based on effect size, direction and/or molecule identity. Selected molecules then underwent a more detailed assessment of senescence phenotypes including proliferation, apoptosis, DNA damage, senescence-associated secretory phenotype (SASP) expression and regulators of alternative splicing. A selection of the molecules demonstrating effects on senescence were then used in a new bioinformatic structure-function screen to identify common structural motifs. 90 molecules displayed altered CDKN2A expression at one or other dose, of which 15 also displayed effects on SAB positivity in primary human dermal fibroblasts. Of these, three were associated with increased SAB activity, and 11 with reduced activity. The female synthetic sex hormones; diethylstilboestrol, ethynyl estradiol and levonorgestrel; were all associated with a reduction in aspects of the senescence phenotype in male cells, with no effects visible in female cells. Finally, we identified that the 30 compounds that decreased CDKN2A activity the most had a common substructure linked to this function. Our results suggest that several drugs licenced for other indications may warrant exploration as future senotherapies, but that different donors and potentially different sexes may respond differently to senotherapeutic compounds. This underlines the importance of consideration of donor-related characteristics when designing drug screening platforms.

Phosphocalcium metabolism disorders have emerged as potential complications in individuals recovering from COVID-19. This abstract provides a concise summary of the current understanding of phosphocalcium metabolism disturbances post-COVID, their prevalence, clinical manifestations, and underlying mechanisms. The impact of COVID-19 on phosphorus, calcium, and parathyroid hormone levels is discussed, highlighting the importance of regular monitoring and appropriate management strategies. The abstract emphasizes the need for further research to enhance our understanding of these disorders and improve post-COVID patient care.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women, characterized by fluid-filled sacs in the ovaries and various symptoms including high androgen levels, endometrial irregularities, and cysts. While the cause of PCOS is unknown, it has been linked to genetic, endocrine, and metabolic factors, and there are several treatment options, including lifestyle modifications, medications, and surgery. Natural products, such as medicinal plants and fruits, are being explored as potential treatments for PCOS due to their bioactive compounds with pharmacological effects related to antioxidant, antimicrobial, anticancer, and antidiabetic properties. Some of these compounds improve insulin sensitivity, reduce inflammation, and enhance glucose metabolism, which is beneficial for women with PCOS. This review examined the effects of natural products on PCOS, including their effects on ovarian histological changes, blood glucose, sex hormones, and lipid profile, based on animal and human studies. This study suggests that the use of natural products as complementary medicine can be a promising resource for the development of effective therapeutics for PCOS, but that further research is needed to fully understand their benefits

The Sry-related HMG-box (Sox) family is a group of transcriptional regulators that play a critical role in many important developmental processes in both vertebrates and invertebrates. In aquatic animals, the function of Sox genes on sexual development has been gained particular attentions. The present study reported the molecular characterization of a Sox member (PtSoxE) in the swimming crab, Portunus trituberculatus, and tissue distribution analysis showed it was male-specific. Since the most highly expression of PtSoxE was found in the androgenic gland (AG), its relation to the insulin-like androgenic gland hormone (IAG) was further investigated. The PtSoxE siRNA caused a significant decrease in IAG expression in both AG and testis, whereas PtSoxE expression could be induced by treating with AG homogenate and rIAG. The result suggested a transcriptional interaction between PtSoxE and IAG. In addition, PtSoxE expression showed a closely positive correlation with several reported spermatogenesis-related genes, suggesting its involvement in testicular development of P. trituberculatus.

Production of lumpfish (Cyclopterus lumpus) has become crucial in controlling sea lice levels in salmonid aquaculture. To improve their breeding, there is a need for early sex identification. The genomic region containing anti-Müllerian hormone (amh) gene was suggested as the candidate sex-determining gene in lumpfish. However, the genome of lumpfish contains three copies of amh with ambiguous sex specificity, designated amh1, amh2, and amh3. The study aims to analyse the male-specific region between these amh paralogues, for its application as a sex marker. In this study, we utilised polymerase chain reaction (PCR)-based assays to identify the male-specific amh markers in lumpfish and estimate the length of the male-specific region in the lumpfish genome. Our results suggest that a region of approximately 26 kilobase (kb) region containing amh1 and amh2 is male-specific, while both sexes share amh3. The developed PCR-based genetic sex identification assays targeting amh1 and amh2 exhibited more than 97% accuracy. Further experiments in other members of the Cyclopteridae: Aptocyclus ventricosus, Eumicrotremus taranetzi, and E. asperrimus revealed male-specific amh fragments only in A. ventricosus. Phylogenetic analyses using the available Cyclopteridae amh sequences suggest that male-specific amh arose early in the Cyclopteridae lineage. These findings and development of the PCR test will be of service to lumpfish aquaculture as well as to future studies attempting to further elucidate the sex-determination system and sex chromosome evolution in lumpfish.

The aim of this study is to describe the cognitive and speech results obtained after growth hormone (GH) treatment and neurorehabilitation in a man that suffered a traumatic brain injury (TBI). 17 months after the accident, the patient was treated with growth hormone (GH), together with neurostimulation and speech therapy. At admission, the left vocal cord revealed paralyzed, in the paramedian position, a situation compatible with a recurrent nerve injury. Clinical and rehabilitation assessments revealed a prompt improvement in speech and cognitive functions, and following completion of treatment, endoscopic examination showed recovery of vocal cord mobility. These results, together with previous results from our group, indicate that GH treatment is safe and effective for helping neurorehabilitation in chronic speech impairment due to central laryngeal paralysis, as well as impaired cognitive functions.

Traumatic brain injury represents one of the main health problems in developed countries. Growth Hormone (GH) and rehabilitation have been claimed to significantly contribute to the recovery of lost motor function after acquired brain injury, but the mechanisms by which this occurs are not well understood. In this work, we have investigated cell proliferation in the piriform cortex (PC) of adult rats with ablation of the frontal motor cortex treated with GH and rehabilitation, in order to evaluate if this region of the brain, related to the sense of smell, could be involved in benefits of GH treatment. Male rats were either ablated the frontal motor cortex in the dominant hemisphere or sham-operated and treated with GH or vehicle at 35 days post-injury (dpi) for five days. At 36 dpi, all rats received daily injections of bromodeoxyuridine (BrdU) for 4 days. We assessed motor function through the paw-reaching-for-food task. GH treatment and rehabilitation at 35 dpi significantly improved the motor deficit caused by the injury and promoted an increase of cell proliferation in the PC ipsilateral to the injury, which could be involved in the improvement observed. Cortical ablation promoted greater number of BrdU+ cells in the piriform cortex that was maintained long-term, which could be involved in the compensatory mechanisms of the brain after injury.

The detection of hormones, pharmaceutical and personal care products (PPCPs), in aqueous complex media as water bodies is an urgent and mandatory matter because of its harmful impact on the environment. This work presents a sensor device which is able to detect trace of the synthetic hormone 17α-ethinylestradiol (EE2), in a range of concentration of 10-15 to 10-9 M in both mineral and tap waters. These types of water were studied due to their different degrees of complexity, which allow to attain a better understanding of EE2’s behavior and response in different media. The sensor body consists of solid supports having interdigitated electrodes without and with a thin film deposited on it, and device response is evaluated through impedance spectroscopy. The thin films were prepared by the layer-by-layer technique from aqueous solutions of polyethylenimine (PEI) and poly(sodium 4-styrenesulfonate) (PSS) polyelectrolytes. Results demonstrated that it is possible to discriminate clearly the different waters used and to detect EE2, obtained from the second principal component (PC2) as a result of the application of principal component analysis method, with a sensitivity of -0.072 ± 0.009 and -0.44 ± 0.03 per decade of concentration, for mineral and tap water, respectively. Detection limits values were found to be of 8.6 fM (2.6 pg/L) and of 7.5 fM (22.2 pg/L) for TW and MW, respectively and are lower than the ones found in literature. Moreover, the achieved constant proportionality between the PC2 values for each EE2 concentration reveals that one can use this methodology to quantify EE2 concentration in unknown aqueous complex matrices.

The present study was conducted to evaluate the effects of dietary supplementation of tea polyphenol （TP） on serum hormone, serum enzyme activity, antioxidant-related and immune-related gene expression of laying hens under heat stress. A total of 288 Chinese yellow chicken (186 days old) were randomly distributed among two treatments, each of which included 6 replicates of 24 hens. Dietary treatments were that the basal diet was supplemented with 200 mg / kg tea polyphenol. The study lasted for 7 weeks, including 1 week of adaptation and 6 weeks of the formal test. The content of high-density lipoprotein cholesterol (HDL-C) and total protein (TP) in serum significantly decreased by dietary supplementation with tea polyphenol. Dietary tea polyphenol supplementation improved serum superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) enzyme activity and decreased serum malondialdehyde (MDA) content in treatments compared to the control. However, supplementation of tea polyphenol did not affect the activity of serum catalase (CAT). The results indicated that long-term feeding of tea polyphenols help to increase the amount of hormones (FSH, E2) associated with reproduction in laying hens and thus improve egg production. It also improved the immune function of laying hens in high temperature environments. Adding tea polyphenols to the diet can significantly increase the serum IgG, IgM content of the laying hens and can upregulate the IgA content. Dietary supplementation of tea polyphenols in the laying hens significantly increased the expression of antioxidant enzyme-related genes (SOD, CAT and GPX1) in the liver. Moreover, the addition of tea polyphenols significantly increased the expression of immune-related genes (Interferon-γ (INF-γ), Interleukin 2 (IL-2) and Interleukin 4 (IL-4)) in the spleen. It is concluded that addition of tea polyphenols has a positive effect on antioxidant activity and immune function of laying hens.

Luteinizing hormone receptor (LHR) is a member of the seven-transmembrane (TM) receptor family. Several mutations in LHR have been identified in many mammalian species, leading to either constitutive activation or inactivation of the receptor. Mutations in highly conserved regions of the TM domain have been reported. In this study, we analyzed signal transduction by three constitutively active mutants (designated M410T, L469R, and D590Y) and two inactivating mutants (D383N and Y546F) of eelLHR known as naturally occurring in human LHR . To directly assess the functional effects of these mutations, site-directed mutant receptors were transiently expressed in CHO-K1 cells and cAMP accumulation stimulated by recombinant eelLH (rec-eelLH) was measured by homogeneous time-resolved fluorescence (HTRF) assays. The cAMP response in cells expressing eelLHR wild-type (eLHR-WT) increased in a dose-dependent manner with rec-eelLH ligand stimulation. Cells expressing the activating eelLHR mutants, M410T, L469R, and D590Y, exhibited a 4.0-, 19.1-, and 7.8-fold increase in basal cAMP response, respectively. However, their maximal responses were approximately 73, 53, and 92%, respectively, of the maximal response of LHR-WT. The L469R mutant exhibited a particularly marked increase in cAMP production in the absence of agonist. The maximal responses of the inactivating mutants, D383N and Y546F, were 32 and 24% of LHR-WT, respectively. However, the inactivating mutations did not completely impair signal transduction. Thus, we report here the first characterization of activating and inactivating mutations in eelLHR and we show that these mutations have similar effects as those reported for mammalian LHRs. Moreover, eelLHR with activating mutations showed constitutive cAMP responses. These results provide important data on the signal transduction of constitutively active and inactive LHR mutants. Further studies should aim to identify the mechanism responsible for the significant increase in basal cAMP response in the constitutively activated eelLHR mutants.

Primary congenital hypothyroidism is readily diagnosed based on elevated plasma TSH levels. In contrast, in the rare disorders of thyroid hormone resistance, TSH and often also thyroid hormone levels are within the normal range. Thyroid hormone resistance is caused by defects in hormone metabolism, transport, or receptor activation and has the same severe consequences for childhood development as congenital hypothyroidism. A total of 23,522 data points from a large cohort of children and young adults were used to generate normal values and sex-specific percentiles for the ratio of free T3 to free T4 (fT3/fT4 ratio). The aim was to determine whether cases with genetically confirmed thyroid hormone resistance (MCT8, THRα, and SECSIBP2 defects) had an abnormal fT3/fT4 ratio. Indeed, we were able to demonstrate a clear separation of patient values for the fT3/fT4 ratio from normal and pathological controls (e.g., children with severe cerebral palsy). We therefore recommend the use of the fT3/fT4 ratio as a readily available screening parameter in children with developmental delay for the identification of thyroid hormone resistance syndromes. The fT3/fT4 ratio can be plotted on centile charts using our free online tool at http://www.thyroid-hormone-ratio.org that accepts various SI and non-SI units.

Since the introduction of Cross-laminated Timber (CLT) in Austria in the early 1990s, the adoption of this 90°-crosswise-laminated product has seen exponential growth worldwide. Compared to traditional laminated timber products (e.g. glulam), CLT provides improved dimensional stability, but with reduced out-of-plane bending stiffness. To improve the bending stiffness, while maintaining relative dimensional stability, a modified orientation of the inner layers in a diagonal direction can be used. This novel product is Diagonal-Cross-laminated Timber (DCLT), a composite timber product, consisting of inner layers which are rotated at different angle-ply orientations between 0 and 90 degrees to the outer layers. To properly model the out-of-plane bending behavior of the DCLT, analytical models and Finite Element Analysis (FEA) were used and the results were validated by third-point bending tests performed on DCLT panels with angle-ply orientations of 10°, 20°, 40°, 70°, and a conventional CLT 90° panel. The results indicate that DCLT panels with angle-ply cross-layers have a structural advantage in out-of-plane bending over traditional CLT (90°) panels. The development of DCLT and its introduction to the industry could enable the use of lower-quality timber that would not otherwise satisfy structural requirements for CLT.

In cross-country skiing the time difference between a race winner and the person coming second is typically very small. Since much of the energy is spent on overcoming resistive forces, a relatively small reduction of these can have a significant impact on the results. The resistive forces come partly from the friction in the tribological interface, between the ski and the snow, and as with many tribological applications the characterisation of its origin, plays an important role in determining the frictional properties. Also in cross-country ski friction, there are several scales impacting the frictional performance, with the major contributors being the ski-camber profile and ski-base structure. Macro-scale measurements of the ski's camber profile under load, are often used to determine how adequate the ski is for a specific condition. The characteristic properties usually obtained are, the force required to collapse the ski to a certain camber height, the topography of the kick-wax zone, and by simple means a determined lengths of the frictional interface, i.e., the apparent contact length. To this date, there are some mathematical models, but there is no robust way of determining the macro-scale contact properties between a cross-country ski and a counter surface using simulations. In the present paper an Artificial neural networks (ANN) is trained to predict the ski-camber profile for various loads placed at different positions, and a well established deterministic approach is used to simulate the contact between the ANN-predicted ski-camber profile and a linearly elastic body with a flat surface, representing the snow. The results suggest that this method is feasible for the determination of the apparent contact characteristics of different skis. Moreover, we show that the apparent contact area does not linearly depend on the load, and that the elastic properties of the counter surface also has a large impact on the apparent contact area and the average apparent contact pressure.

The purpose of this study was to analyze the cross-linguistic influence of previously learned languages and working memory capacities on the vocabulary performance of two different typological languages. The objectives of this study were (1) to compare the working memory capacities of bilingual adults in relation to the vocabulary performance of two different languages never learned by the participants, and (2) to analyze to what extent the typology of previously learned languages influences working memory capaci-ties in relation to the vocabulary performance of French and Nahuatl. A group of 43 Mexican-Spanish college students participated in this experimental study. The participants completed a series of working memory tasks in Nahuatl and French. The results showed that working memory capacities were lower in Nahuatl than in French. Thus, a correlation was found between their first and second language and vo-cabulary performance in French. We can consider the influence of previously learned languages as a significant factor in vocabulary acquisition in accordance with the participants' working memory capacities.

We formulate a more straightforward, symmetry-based techniques in manually computing the determinant of any n×n matrix by revisiting Dodgson’s condensation method and strategically applying elementary row operations and the definition and properties of determinants. The result yields a more simplified mnemonical algorithm than the usual reduction by elementary row operations and co-factor expansion and with minimal terminal divisions performed compared to Dodgson’s internal divisions.

This article presents the results of a cross-disciplinary applied study exploring investors’ protections in the context of distributed ledger technology (DLT) smart contracts. Fusing legal, business, and technical perspectives, we developed a framework for protection from non-commercial risks for stablecoins, taking advantage of DLT and AI. A key concept we propose is the monitoring of disinformation and fake news to prevent malicious parties from abusing our solution. Based on the similarities between central bank digital currencies (CBDCs) and stablecoins, we propose scaling up our results to all future internet investments performed without face-to-face contact between the investor and the company.

The danger is still very large from cross site scripting attacks. When designing web applications We must follow as much as we can prevention rules and don’t leave any loophole to our programs. Experience is a great factor for programmers to know these attacks and for a trainee programmer is a difficult task to spot all the weak points. In this article we present a tutorial on launching an XSS attack and also we propose simple solutions.

Sentinel-1 (S1) extra-wide (EW) swath data in cross-polarization (horizontal-vertical, HV or vertical-horizontal, VH) are strongly affected by the scalloping effect and thermal noise, particularly over areas with weak backscattered signals, such as sea surfaces. Although noise vectors in both the azimuth and range directions are provided in the standard S1 EW data for subtraction, the residual thermal noise still significantly affects sea ice detection by the EW data. In this paper, we improve the denoising method developed in previous studies to remove the additive noise for the S1 EW data in cross-polarization. Furthermore, we propose a new method for eliminating the residual noise (i.e. multiplicative noise) at the sub-swath boundaries of the EW data, which cannot be well processed by simply subtracting the reconstructed 2-D noise field. The proposed method of removing both the additive and multiplicative noise was applied to EW HV-polarized images processed using different Instrument Processing Facility (IPF) versions. The results suggest that the proposed algorithm significantly improves the quality of EW HV-polarized images under various sea ice conditions and sea states in marginal ice zone (MIZ) of the Arctic. This is of great support for the utilization of cross-polarization SAR images in wide swaths for intensive sea ice monitoring in polar regions.

Chikungunya virus (CHIKV) is an alphavirus that causes febrile illness punctuated by severe polyarthralgia. After the emergence of CHIKV in the Western Hemisphere, multiple reports of congenital infections were published that documented neurological complications, cardiac defects, respiratory distress, and miscarriage. The Western Hemisphere is endemic to several alphaviruses and whether antigenic cross-reactivity can impact the course of infection has not been explored. Recent advances in biomedical engineering have produced cell co-culture models that replicate the cellular interface at the maternal fetal axis. We employed a trans-well assay to determine if cross-reactive antibodies affected the movement and replication of CHIKV across placental cells and into an embryoid body. The data show that antibodies to Venezuelan equine encephalitis virus (VEEV) significantly reduced CHIKV viral load in embryoid bodies. The data highlight that viral pathogenesis can be cell-specific and that exploiting antigenic cross-reactivity could be an avenue for reducing the impact of congenital CHIKV infections.

Drug resistance in melanoma is a major hindrance in cancer therapy. Growth hormone (GH) plays a pivotal role in contributing to resistance to chemotherapy. Knocking down or blocking the GH receptor has been shown to sensitize the tumor cells to chemotherapy. Extensive studies have demonstrated that exosomes, a subset of extracellular vesicles, play an important role in drug resistance by transferring key factors to sensitize cancer cells to chemotherapy. In this study, we explore how GH modulates exosomal cargoes from melanoma cells and their role in drug resistance. We treated the melanoma cells with GH, doxorubicin, and GHR antagonist, pegvisomant, and analyzed the exosomes released. Additionally, we administered these exosomes to recipient cells. The GH-treated melanoma cells released exosomes with elevated levels of ABC transporters (ABCC1 and ABCB1), N-cadherin and MMP2, enhancing drug resistance and migration in recipient cells. GHR antagonism reduced these exosomal levels, restoring drug sensitivity and attenuating migration. Overall, our findings highlight a novel role of GH in modulating exosomal cargoes that drive chemoresistance and metastasis in melanoma. This understanding provides insights to the mechanisms of GH in melanoma chemoresistance and suggests GHR antagonism as a potential therapy to overcome chemoresistance in melanoma treatment.

Piceatannol (PIC), a natural analog of resveratrol, has various biological functions. We previously reported that PIC had an anti-obesity effect only in ovariectomized mice. While ovariectomized mice have low phosphorylation levels of hormone-sensitive lipase (pHSL) at Ser563, we found that PIC increased those levels. Here, we investigated the effect of PIC using 3T3-L1 adipocytes to clarify the mechanism by which PIC activates HSL. First, PIC was confirmed to induce HSL phosphorylation at Ser563 in 3T3-L1 cells as in vivo experiments showed. pHSL (Ser563) is believed to be activated through the β-adrenergic receptor (β-AR) and protein kinase A (PKA) pathway; however, the addition of a selective inhibitor of β-AR did not inhibit the effect of PIC. The addition of PKA inhibitor with PIC blocked pHSL (Ser563), suggesting that PIC’s effects are mediated by PKA from a different pathway than β-AR. The addition of G15, a selective inhibitor of the G protein-coupled estrogen receptor (GPER), lowered HSL activation by PIC. Furthermore, PIC inhibited insulin signaling and did not induce pHSL (Ser565), which represents its inactive form. This study is the first to suggest that the GPER pathway might regulate HSL activation in adipocytes.

Red palm weevils (RPWs) are a major pest to coconut and palm trees, causing significant economic losses in many countries. The current control method involves using insecticides, which are unsustainable and environmentally damaging. Thus, it is necessary to develop an eco-friendly and sustainable approach to mitigate the RPW problem. Our studies have revealed that feeding RPWs with food containing specific herbs can affect the weevils' mutualistic relationship with gut microbiota or their growth hormones, resulting in a notable reduction in the metamorphosis rate at the pupation stage. For instance, the addition of Kra-jeab (a roselle Hibiscus sabdariffa) and Kra-pao (a holy basil Ocimum tenuiflorum) led to a reduction of 76.7% and 75.6%, respectively, in the metamorphosis rate, while combining the two herbs resulted in a higher reduction rate of 86.7%. In addition to these findings, altering their pupation nature by reducing the fiber length used in RPW feed to less than 1 centimeter can stop the weevil’s pupation entirely. These findings demonstrate the potential application of biological and physical factors to reduce RPWs' metamorphosis rate and control their destructive impact on palm industries, thus providing a promising solution for the conflict between palm and insect farmers.

Chagas disease (CD) is one of the most devasting parasitic diseases in the Americas affecting 7 to 8 million people worldwide. In vitro and in vivo experiments have demonstrated that decreased growth hormone (GH) serum levels occur as CD progresses. Interestingly, inactivating mutations in the GH receptor in humans induce Laron syndrome (LS), a clinical entity characterized by increased GH and decreased insulin growth factor-1 (IGF-1) serum levels. The largest cohort of LS subjects lives in the southern provinces of Ecuador. Remarkably, CD prevalence in these individuals is diminished despite living in highly endemic areas. In the current ex vivo study, we employed serum from GHR -/- mice, also known as LS mice (a model of GH resistance with high GH and low IGF-1 levels), and serum from bovine GH (bGH) transgenic mice (high GH and IGF-1), to test the effect on T. cruzi infection. We infected mouse fibroblast L-cells treated with serum from each type of mouse with metacyclic trypomastigotes from Trypanosoma cruzi (etiological CD infectious agent). Treatment with GHR-/- serum (LS mice) significantly decreased infection by 28% compared to 48% seen in control wild-type mouse serum (WT). Treatment with bGH mouse serum significantly decreased infection by only 41% compared to 54% from WT controls. Our results suggest that high GH and low IGF-1 in blood circulation, as typically seen in LS individuals, confers partial protection against T. cruzi infection.

Increasingly, conservation genetics pinpoint the use of biological matrices collected without stressing wildlife. Cervid’s antlers seem to fit with this need. We verified the amplification success rate from DNA obtained from red deer antlers collected in the State Nature Reserve of Bosco della Mesola, Northern Italy and its use for conservation purposes. Here occurs the only native red deer population of peninsular Italy, recently recognized as a distinct subspecies (Cervus elaphus italicus). Four antlers stored at room temperature for four years and four samples highly degraded by environmental conditions were analyzed using a multimarker approach. We utilized a simple, inexpensive method to extract DNA from drilled antlers powder. This study confirms that weathered antlers can be a suitable source of DNA also in Mediterranean climate characterized by strong seasonal fluctuations, and not only in dry climates. Our results pointed out that only burr drilling yielded good quality amplifiable DNA. Antlers can be used in particular for molecular genetic studies on rare or threatened species of cervids as providing an efficient and cost-effective non-invasive sampling.

Previously we demonstrated, in rats, that the treatment with growth hormone (GH) and rehabilitation, carried out immediately after a motor cortical ablation, significantly improved the motor affectation produced by the lesion and induced the re-expression of nestin in the contralateral motor cortex. Here we analyze cortical proliferation after ablation of the frontal motor cortex and investigate the re-expression of nestin in the contralateral motor cortex and the role of the striatum and thalamus in motor recovery. The rats were subjected to ablation of the frontal motor cortex in the dominant hemisphere or sham-operated and immediately treated with GH or vehicle (V), for five days. At 1 dpi (days after injury), 5 rats received daily injections (4 days) of bromodeoxyuridine and were sacrificed. The other 15 rats (n = 5 / group) underwent treatment and rehabilitation and were sacrificed at 25 dpi. GH induced the greatest number of proliferating cells in the perilesional cortex. GH and rehabilitation produced the functional recovery of the motor lesion and increased the expression of nestin in the striatum. In the thalamic ventral nucleus ipsilateral to the lesion, cells positive for nestin and actin were detected, but this was independent of GH. Our data suggest that GH-induced striatal nestin is involved in motor recovery.

In California, an average of 41,900 patients are diagnosed annually with Staphylococcus bacterial infection; out of these, 24,090 patients have methicillin-resistant Staphylococcus aureus (MRSA) infection and 17,810 patients have methicillin-sensitive Staphylococcus aureus (MSSA) infection. The aim of this paper is to find out whether there is a significant difference in strain dominancy and in what direction. The paper gathered and analyzed data for period of five years of infection rate due to Staphylococcus aureus. This study indicates that a significant difference in dominancy exists, the MRSA infection rate (an average of five years period) is 1.35 times higher than the MSSA infection rate (P-value < 0.05, CI: 95%), but the gap between the two infection rates is decreasing. The infection rate of both MRSA and MSSA is in a path of decline.

1) Background: We analyzed, by PET-SCAN, how growth hormone (GH) could act on the brain of an older woman, not GH-deficient, which was beginning to show some cognitive deficiencies and presented an ApoE genotype 4/3; 2) Methods: After performing a first psychometric study (TAVEC verbal learning test), the metabolic activity of brain structures related to knowledge, memory, and behavior was analyzed using 18-F Fluorodeoxyglucose PET-SCAN. The patient was then treated with GH (0.4 mg/day) for three weeks and on the last day under this treatment, a new PET-SCAN was performed. One month after beginning treatment with GH, a new TAVEC test was performed; 3) Results: GH administration normalized the cognitive deficits observed in the first psychometric test and increased significantly (P < 0.025) the metabolic activity in practically all brain cortical areas, specifically in the left hippocampus and left amygdala, although not in the left parahippocampus; and 4) Conclusions: This is the first study in which the positive effects of GH on cerebral metabolism have been visualized in a human patient. Our data confirm the positive effects of this hormone on cognition, memory and behavior in patients affected by mild cognitive impairments.

Background: Low T3 syndrome occurs frequently in patients with sepsis. Type 3 deiodinase (Dio3) is present in immune cells but there is no description of its presence in this patients. Here we aimed to determine the prognostic impact of thyroid hormones levels (TH) measured on ICU admission on mortality and on evolution to chronic critical illness (CCI) and the presence of D3 in white cells. Methods: Prospective cohort study with a follow-up for 28 days or deceased. Results: Low T3 levels at admission were present in 86.5% of the patients. Dio3 was 55% induced in immune cells. The cut-off value of 60 pg/mL for T3 displayed a sensitivity and specificity of 81% and 64% for predicting death, odds ratio of 4.89. Lower T3 yielded an area under the receiver operating characteristic curve of 0.76 and 0.75 for mortality and evolution to CCI, respectively, thus displaying better performance than commonly used prognostic scores. Conclusions: We advance in the pathophysiology of low T3 showing induced D3 in immune cells during sepsis. Low T3 levels independently predicted a progression to CCI and mortality within 28 days in sepsis and septic shock.

Plants harbor a large diversity of endophytic microbes. Meadow fescue (Festuca pratensis) is a cool-season grass known for its symbiotic relationship to the systemic and vertically- via seeds - transmitted fungal endophyte Epichloë uncinata but the effect of the endophyte on the microbial endophyte community and phytohormones is largely unexplored. Here, we sequenced the endophytic bacterial and fungal communities in the leaves and roots, analyzed phytohormone concentrations and plant performance parameters in Epichloë-symbiotic (E+) and Epichloë-free (E-) individuals of two meadow fescue cultivars. The endophytic leaf microbial community differed between leaf and root tissues independent of endophyte symbiosis while the fungal community was different in leaves of Epichloë-symbiotic and Epichloë-free plants in both cultivars. At the same time, endophyte symbiosis decreased salicylic acid and increased auxin concentrations in leaves. Epichloë-symbiotic plants showed a higher biomass, chlorophyll content (SPAD) and higher seed mass at the end of the season. Our results demonstrate that Epichloë-symbiosis alters the leaf fungal microbiome, which coincides with changes in phytohormone concentrations, indicating that Epichloë endophytes affect both, plant immune responses and other fungal endophytes. Whether the effect of Epichloë endophytes on other fungal endophytes is connected to changes in the phytohormone concentrations remains to be elucidated.

Viroids are known the smallest plant pathogens, and although their genome sequences do not encode proteins, they can cause disease in economically important crops. In order to control viroid diseases and mitigate their damage, genetic resources used for breeding of the viroid-resistant crop have been searched, but the practical resistant trait has not been found in almost all viroid-crop combinations, as well as the tolerant trait. Due to the difficulty in exploiting naturally occurring resistance or tolerance, various effective strategies have been devised to control viroid diseases using non-transforming or transforming techniques. Meanwhile, extensive findings related to viroid resistance and tolerance may lead to confer resistance or tolerance to viroid infection by combining with the recently emerged new technologies (e.g., spray-induced gene silencing and genome-editing technologies), which are believed to be more environmentally viable and acceptable to the general public than previously reported approaches. In particular, some genome-modified crops produced by the latter technology are already on the market. In this review, we comprehensively summarize the current status about investigation of naturally occurring genetic traits for viroid resistance and tolerance, accumulating knowledge about host factors involved in viroid pathogenicity, and various basic technologies developed to try to possible viroid disease control strategies. Furthermore, we discuss prospects and challenges for the achievement of more effective, practical, and sustainable disease control of viroid.

Several observational studies have indicated the potential associations between calcium, vitamin D(Vit-D) and irritable bowel syndrome (IBS). However, the causal relationship deduced from these studies is subjected to residual confounding factors and reverse causation. Therefore, we aim to explore the bidirectional causal effects between serum calcium, Vit-D, PTH and IBS at the genetic level by a two-sample Mendelian randomization (MR) analysis. Sensitivity analyses were performed to evaluate the robustness. The estimates were presented as odds ratio (OR) with their 95% confidence intervals (CIs). The results of the inverse-variance-weighted method did not re-veal any causal relationship shared between genetically predisposed calcium (OR = 0.92, 95% CI: 0.80-1.06, P = 0.25) and Vit-D (OR = 0.99, 95% CI: 0.83-1.19, P = 0.94) level and the risk of IBS. The bidirectional analysis demonstrated that genetic predisposition to IBS was associated with a de-creased level of PTH (beta: -0.19, 95%CI: -0.34 to -0.04, P = 0.01). In conclusion, the present study indicates no causal relationship between the serum calcium and Vit-D concentrations and the risk of IBS. The potential mechanisms by which IBS affects serum PTH need to be further investigated.

Dominance hierarchies are ubiquitous in invertebrates and vertebrates, but little is known on how genes influence dominance rank. Our gaps in knowledge are specifically significant concerning female hierarchies and in insects. To start filling these gaps we studied the social bumble bee Bombus terrestris, in which social hierarchies among females are common and functionally significant. Dominance rank in this bee is influenced by multiple factors, including juvenile hormone (JH) that is a major gonadotropin in this species. We tested the hypothesis that the JH responsive transcription factor Krüppel homologue 1 (Kr-h1) mediates hormonal influence on dominance behavior in the bumble bee. We first developed and validated a perfluorocarbon nanoparticles-based RNA interference protocol for knocking down Kr-h1 expression. We then used this procedure to show that Kr-h1 mediates the influence of JH not only on oogenesis and wax production, but also on aggression and dominance rank. To the best of our knowledge, this is the first study causally linking a gene to dominance rank in social insects, and one of only a few such studies in insects or in female hierarchies. These findings are important for determining whether there are general molecular principles governing dominance rank across gender and taxa.

Ovarian hypofunction or primary ovarian insufficiency (POI) is a common cause in the etiology of female infertility. It is a heterogeneous disorder, affecting approximately 1% of women before the age of 40. The characteristics of POI are menstrual disorders, including amenorrhea and delayed menstruation, accompanied by a raised gonadotrophin level and decreased estradiol level. In recent years, electrophysiology (EP) technology has been advancing rapidly in the diagnosis and treatments of numerous diseases. According to studies, bioelectrical stimulation (BES) therapy is an electrophysiology technology that plays significant roles in numerous diseases, including on the thin endometrium in patients with POI. In this review, the overall research progress of this electrophysiological technology has been discussed in relation to the advancement of primary ovarian insufficiency.

Recent advancements in machine learning have ushered in innovative techniques for augmenting datasets, particularly through contrastive learning in the computer vision domain. This study pioneers the application of contrastive learning for sentiment analysis, introducing a novel approach termed EmoConLearn. By fine-tuning contrastive learning embeddings, EmoConLearn significantly surpasses BERT-based embeddings in sentiment analysis accuracy, as evidenced by our evaluations on the DynaSent dataset. This research further delves into the efficacy of EmoConLearn across various domain-specific datasets, highlighting its versatility. Additionally, we investigate upsampling strategies to mitigate class imbalance, further enhancing EmoConLearn's performance in sentiment analysis benchmarks.

Background: Given the extensive translation of the Prolapse Quality of Life Questionnaire (P-QoL) into many languages, it is imperative to develop an Arabic version to facilitate study on Pelvic organ health within the Arabian culture. Objective: To investigate, cross culturally adapt and validate Arabic version of the P-QoL. Study Design: Cross-cultural adaptation and psychometric testing. Methods: A total of 90 participants were included in the study. This cross-sectional study went through two phases; during phase I, the P-QoL was translated and adapted from English into Arabic. The Arabic version was psychometrically validated during phase II using the test-retest reliability internal consistency with Cronbach’s alpha coefficient, convergent construct validity (CC) among the four study tools using Spearman’s coefficient (r) and discriminative validity using Mann-Whitney test to find differences between the means of the two samples. Results: A satisfactory level of semantic, conceptual, idiomatic, and content comparability was reached in the cross-cultural adaptation of the Arabic version of the P-QoL questionnaire. The internal consistency was high in terms of psychometric validation, with a Cronbach’s alpha coefficient of 0.971 for the P-QoL questionnaire. The test-retest results showed a high reliability with interclass correlation coefficient (ICC) of P-QoL = 0.987. The convergent construct validity was highly accepted (moderately strong), reflecting a positive correlation between the Arabic version of the P-QoL and the Australian Pelvic Floor Dysfunction Questionnaire (APFD) r = 0.68 (p &lt; 0.001). Similarly, a significant convergent validity of P-QoL Arabic version and Visual Analogue Scale (VAS) r = 0.47 (p &lt; 0.001) was found, as well as the correlation between the APFD and the VAS r = 0.46 (p &lt; 0.001). However, there were no significant correlation between the SF-12, the P-QoL, the APFD, and the VAS. Conclusion: Based on a significant correlation between the Arabic APFD and the VAS, the results reveal good reliability, internal consistency, and construct validity. It is recommended that Arabic-speaking females with pelvic organ prolapse use the Arabic version of the P-QoL. More research is needed to assess the responsiveness of the P-QoL.

Background: Abdominal wall hernias are a common condition that is seen in daily general surgery patients. However, still more researches are needed to be conducted regarding hernias. The aim of this study is to see the prevalence of hernias among patients admitted to the Department of Surgery of a tertiary care center. Methods: A descriptive cross-sectional study was performed among patients who admitted to the department of surgery in a tertiary care center between 1 August 2023 and 20 September 2023. All patients data were extracted to an excel sheet. Results: We had 760 patients who visited in this period. Only 272 patients (27.9 %) were diagnosed with hernias. We found 52.6 % of patients were male and 47.4 % of patients were female. The age between 46- 60 years old was the most to have hernias (97 patients). Inguinal hernias were the common among other types. Diabetes mellitus, hypertension, COPD, and hydrocele were found in 10.7 % of all patients. Conclusion: The prevalence of hernias in this study was nearly to other studies that conducted in the same conditions. Early diagnosis and patient’s education are the corner stone to prevent morbidities and mortalities.

In the recent decades, per- and polyfluoroalkyl substances (PFAS) have garnered widespread public attention due to their persistence in the environment and detrimental effects on the health of living organisms, spurring the generation of several transcriptome-centered investigations to understand the biological basis of their mechanism. In this study, we collected 2144 publicly available samples from 7 distinct animal species to examine the molecular responses to PFAS exposure and to determine if there are conserved responses. Our comparative transcriptional analysis revealed that exposure to PFAS is conserved across different tissues, molecules and species. We identified and reported several genes exhibiting consistent and evolutionarily conserved transcriptional response to PFAS, such as ESR1, HADHA and ID1, as well as several pathways including lipid metabolism, immune response and hormone pathways. This study provides the first evidence that distinct PFAS molecules induce comparable transcriptional changes and affect the same metabolic processes across inter-species borders. Our findings have significant implications for understanding the impact of PFAS exposure on living organisms and the environment. We believe that this study offers a novel perspective on the molecular responses to PFAS exposure and provides a foundation for future research into developing strategies for mitigating the detrimental effects of these substances in the ecosystem.

This research has critically argued that a vigilant combination of flexibility and certainty in spatial planning can bring about the most optimum planning outcomes. Therefore, to reproachfully evaluate the core argument, this research has tried to empirically respond to the research question of which balance of government intervention and market freedom produces the optimal economic, social and spatial outcomes. This research question has been further translated into an associated central hypothesis i.e., a hybrid planning system with an optimal balance between discretionary and regulatory planning approach can bring about the desired economic, social, and spatial outcomes.

Registry and survey data gave an opportunity to compare possible roles of social attitudes and social values in control and limit the COVID-19 pandemic. We analysed social values and time series of daily R0 (reproduction rate) estimates for 27 European countries. Embedded and affective autonomy are significantly negatively associated (p-Value<0.05) with controlled R0. It could mean that well interconnected societies with high attention to maximize utilities are more likely to couple with COVID-19. Hierarchy is significantly positively associated (p-Value<0.05) with controlled R0. Thus, hierarchical structures could inhibits control of COVID-19. The results emphasize the need to pay more attention to social values context in evaluating the effectiveness of mitigation strategies internationally.

There is tremendous interest, in the economic literature, for the determinants of firms’ capital structure decisions. A rich body of empirical works now exists that purports to identify firm- and country-level factors affecting firms’ financing patterns. In addition, more recently, a new stream of studies has emerged that investigates cross-regional variation in small firms’ capital structure. While small firms’ leverage does seem to vary across regions, at least in countries where significant regional differences in economic and financial development and in the quality of institutions exist, not much yet is known about variation in debt maturity, in debt in relation to equity, and between different types of small firms. The present paper aims to fill this gap through an empirical analysis of cross-regional variation in the capital structure of a sample of about 30,000 Italian small firms over a 13-year period, including the aftermath of the credit crunch that followed the 2007-8 global financial crisis. The findings confirm the view that small firms in underdeveloped regions are more financially constrained, but also amend some of the results shown in the literature, in particular by showing how small firms in Italy’s Southern regions have higher levels of equity and fixed assets than small firms in other regions.

As digitalization expands across all sectors, the economic toll of software defects on the U.S. economy reaches up to $2.41 trillion annually. High-profile incidents like the Boeing 787-Max 8 crash have shown the devastating potential of these defects, highlighting the critical importance of software testing within quality assurance frameworks. However, due to its complexity and resource intensity, the exhaustive nature of comprehensive testing often surpasses budget constraints. This research utilizes a machine learning (ML) model to enhance software testing decisions by pinpointing areas most susceptible to defects and optimizing scarce resource allocation. Previous studies have shown promising results using cost-sensitive training to refine ML models, improving predictive accuracy by reducing false negatives through addressing class imbalances in defect prediction datasets. This approach facilitates more targeted and effective testing efforts. Nevertheless, the generalizability of these models across different projects (cross-project) and programming languages (cross-language) remained untested. This study validates the model's applicability across diverse development environments by integrating various datasets from distinct projects into a unified, using a more interpretable ML approach. The results demonstrate that ML can support software testing decisions, enabling teams to identify up to seven times more defective modules with the same testing effort as a benchmark.

The cDNA sequences of the common gonadotrophic hormone α-subunit (ag-GTHα) and 13 of the specific follicle-stimulating hormone β-subunit (ag-FSHβ) of the giant Amazonian fish Ara-14 paima gigas, have been previously isolated by our research group. A synthesis of ag-FSH in HEK293 15 cells and its purification and preliminary characterization were also carried out. In the present work, 16 ag-FSH was obtained and purified from the same host cells and an extensive physical chemical 17 characterization was performed via RP-HPLC, HPSEC and MALDI-TOF-MS. Ag-FSH, when com-18 pared to human FSH (hFSH), showed a higher hydrophobicity by RP-HPLC and a higher molecular 19 mass (MM) via HPSEC. The same higher MM was also confirmed via MALDI-TOF-MS: 35,353 Da 20 for ag-FSH against 31,969 Da for hFSH. Its immunological activity was also confirmed via an hFSH 21 ELISA, in comparison with the highly purified pituitary preparation of hFSH-AFP7298A, from the 22 National Hormone and Pituitary Program (NHPP-USA). Finally, an in-vitro bioassay, based on the 23 stimulated release of 11-ketotestosterone (11-KT) from immature A. gigas testis, quantified its bio-24 logical activity in comparison with human chorionic gonadotropin (hCG) and with the WHO Inter-25 national Standard of recombinant hFSH (NIBSC-08/282) This suggests that injections of ag-FSH in 26 A. gigas and ag-FSH cDNA Gene Therapy applications should improve the reproductive functions 27 of this threatened species.

Obesity is one of the most prevalent chronic diseases and has become a global epidemic. Obesity leads to a greater risk of breast cancer (BC), metastases, recurrence, and decreased survival. For sustained weight loss, bariatric surgery is effective as a long-term solution. Bariatric surgery is associated with improved outcomes of several cancers including BC, although the mechanisms mediating this protection are unknown. We hypothesized that elevated bile acid pools detected after bariatric surgery may be factors that contribute to improved BC outcomes. Indeed, patients with greater expression of the bile acid receptor FXR displayed improved survival in specific BC subtypes. Patients with tumors that are estrogen receptor negative (ER-) displayed significantly elevated survival with higher FXR (NR1H4) expression compared to lower expression. FXR is a nuclear hormone receptor activated by bile acids. Therefore, we posited that activating FXR using an established FDA-approved agonist would display anticancer effects. Indeed, FXR agonism by the bile acid mimetic known commercially as OCALIVA (“OCA”), or Obeticholic acid (INT-747), significantly reduced BC progression and overall tumor burden in a pre-clinical model. In human and murine BC analyses in vitro, agonism of FXR significantly and dose-dependently inhibited proliferation, migration, and viability. In contrast, synthetic agonism of another common bile acid receptor, the G protein-coupled bile acid receptor (GPBAR1, TGR5) which is mainly activated by secondary bile acids, failed to significantly alter cancer cell dynamics. In conclusion, agonism of FXR by primary bile acid memetic OCA yields potent anti-tumor effects potentially through inhibition of proliferation and migration and reduced cell viability. Findings suggest that FXR is a tumor suppressor gene with high potential for personalized therapeutic strategies for individuals with BC.

Objective: To analyze the relation between alterations in the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis during the first 6 months of life and weight in children born in the Lower Middle São Francisco region. Methods: This is an analytical cohort, with a quantitative approach and a translational perspective. Thirty children with low and normal birth weight were initially identified in a hospital and reapproached at 3 and 6 months of age. Birth weight and alterations in GH/IGF-1 curves at birth, third month, and sixth month of life. Results: Weight gain during the 6 months of follow-up in newborns with low birth weight was greater compared to newborns with normal birth weight. All children who were born with low birth weight had an altered GH/IGF-1 curve at birth (p = 0.002). Most newborns with low birth weight maintained the alteration in the GH/IGF-1 curve at the third month of life (p = 0.027). Regarding the GH/IGF-1 curve at the sixth month, alteration persisted in greater proportion among children with low birth weight. Conclusion: Alterations in insulin resistance markers, demonstrated by increased GH without a proportional increase in IGF-1, were observed to be significant in children with low birth weight, with greater adiposity in this group, which may increase the risk of metabolic diseases in later life.