Open-label, dose-escalation FIGHT-101 study of pemigatinib combined with targeted therapy, chemotherapy, or immunotherapy in patients with advanced malignancies.

BACKGROUND: Pemigatinib is an oral, potent, selective fibroblast growth factor receptor (FGFR) 1-3 inhibitor. FIGHT-101, a three-part, open-label, first-in-human, phase I/II study (NCT02393248), evaluated pemigatinib in patients with advanced solid tumors. In parts 1 and 2, pemigatinib monotherapy had a manageable safety profile and antitumor activity in FGFR-altered tumors. Part 3 (pemigatinib combination therapies) results are presented here. PATIENTS AND METHODS: Patients received 9, 13.5, or 20 mg oral once-daily pemigatinib on continuous or intermittent schedules with gemcitabine and cisplatin (pemi/gem/cis), docetaxel (pemi/doc), trastuzumab (pemi/tras), pembrolizumab (pemi/pembro), or retifanlimab (pemi/reti) irrespective of whether the tumor was confirmed as FGFR altered. Primary endpoints were safety and pharmacodynamics. Secondary endpoints were investigator-assessed tumor objective response rates (ORRs) and pharmacokinetics (PK). RESULTS: Of 65 enrolled patients (pemi/gem/cis, n = 8; pemi/doc, n = 7; pemi/tras, n = 6; pemi/pembro, n = 26; pemi/reti, n = 18), all discontinued. Treatment-emergent adverse events (TEAEs) were generally consistent with individual drug AEs. Serious and grade ≥3 TEAEs occurred in 0%-85.7% and 33.3%-100.0% of patients across treatment groups, respectively. All pemigatinib combinations demonstrated steady-state PK comparable to monotherapy. Pharmacodynamic effects in all pemigatinib combinations, except pemi/gem/cis, were consistent with monotherapy. Less inhibition of FGFR2α phosphorylation was observed with this combination. ORRs (95% confidence interval) were 37.5% [8.5% to 75.5% (pemi/gem/cis)], 14.3% [0.4% to 57.9% (pemi/doc)], 0% (pemi/tras), 26.9% [11.6% to 47.8% (pemi/pembro)], and 11.1% [1.4% to 34.7% (pemi/reti)]. All groups had instances of tumor shrinkage. ORRs in assessable patients with FGFR rearrangements and mutations were 50% and 33%, respectively. CONCLUSIONS: Pemigatinib combination therapy showed no unexpected toxicities. PK and pharmacodynamics were mostly consistent with pemigatinib monotherapy. Pemi/gem/cis (37.5%) and pemi/pembro (26.9%) had the highest ORR; most responders had FGFR alterations.

Prenatal EDC exposure, DNA Methylation, and early childhood growth: A prospective birth cohort study.

BACKGROUND: Exposure to endocrine-disrupting chemicals (EDCs) has been found to be associated with growth and developmental abnormalities in children. However, the potential mechanisms by which exposure to EDCs during pregnancy increases the risk of obesity in children remain unclear. OBJECTIVE: We aimed to explore associations between prenatal EDC exposure and the body mass index (BMI) of children at age two, and to further explore the potential impact of DNA methylation (DNAm). METHOD: This study included 285 mother-child pairs from a birth cohort conducted in Wuhan, China. The BMI of each child was assessed at around 24 months of age. The concentrations of sixteen EDCs at the 1st, 2nd, and 3rd trimesters were measured using ultra-high performance liquid chromatography coupled to a triple quadrupole mass spectrometer. The research utilized general linear models, weighted quantile sum regression, and Bayesian Kernel Machine Regression to assess the association between prenatal EDC exposure and childhood BMI z-scores (BMIz). Cord blood DNAm was measured using the Human Methylation EPIC BeadChip array. An epigenome-wide DNAm association study related to BMIz was performed using robust linear models. Mediation analysis was then applied to explore potential mediators of DNAm. RESULTS: Urinary concentrations of seven EDCs were positively associated with BMIz in the 1st trimester, which remained significant in the WQS model. A total of 641 differential DNAm positions were associated with elevated BMIz. Twelve CpG positions (annotated to DUXA, TMEM132C, SEC13, ID4, GRM4, C2CD2, PRAC1&PRAC2, TSPAN6 and DNAH10) mediated the associations between urine BP-3/BPS/MEP/TCS and elevated BMIz (P < 0.05). CONCLUSION: Our results revealed that prenatal exposure to EDCs was associated with a higher risk of childhood obesity, with specific DNAm acting as a partial mediator.

Life-history of the spiny butterfly ray, Gymnura altavela (Chondrichthyes: Myliobatiformes), kept under human care in a marine aquarium.

The Rio de Janeiro Marine Aquarium (AquaRio) is the first to successfully maintain and reproduce the spiny butterfly ray (Gymnura altavela), providing unique information about the species' biology. Seven rays were kept in captivity between 2018 and 2023, two captured on the southeastern coast of Brazil and five born in the aquarium. The applied abiotic conditions and nutrition allowed for the survival, growth, and reproduction of these individuals. Growth parameters (asymptotic disk width-DW∞ and growth coefficient-k) were estimated based on the von Bertalanffy model using the Fabens method for males and females separately. The best models estimated DW∞ = 106.47 cm and k = 0.396 for males and DW∞ = 172.2 cm and k = 0.190 for females. Sexual dimorphism was corroborated, with females reaching larger sizes and presenting slower growth rates than males. The estimated k values were higher than those estimated for rays of similar size to G. altavela in the natural environment, probably due to the constant water temperature (around 25.5°C), food abundance, low population density, reduced predation rates, and high water quality in the captive environment. A comparison of the captivity findings with other studies on G. altavela age and growth in the Atlantic and Mediterranean indicates a broad phenotypic plasticity regarding growth. Three G. altavela reproductions were recorded, with size at birth appearing to be a key factor for pup's survival. Behavioral pattern observations associated with reproduction are also described, encompassing chasing and copulation, whereas the species' internal morphology is described through coelomic cavity ultrasound scanning.

Requirement of Pdgfrα+ cells for calvarial bone repair.

Platelet-derived growth factor receptor α (PDGFRα) is often considered as a general marker of mesenchymal cells and fibroblasts, but also shows expression in a portion of osteoprogenitor cells. Within the skeleton, Pdgfrα+ mesenchymal cells have been identified in bone marrow and periosteum of long bones, where they play a crucial role in participating in fracture repair. A similar examination of Pdgfrα+ cells in calvarial bone healing has not been examined. Here, we utilize Pdgfrα-CreERTM;mT/mG reporter animals to examine the contribution of Pdgfrα+ mesenchymal cells to calvarial bone repair through histology and single-cell RNA sequencing (scRNA-Seq). Results showed that Pdgfrα+ mesenchymal cells are present in several cell clusters by scRNA-Seq, and by histology a dramatic increase in Pdgfrα+ cells populated the defect site at early timepoints to give rise to healed bone tissue overtime. Notably, diphtheria toxin-mediated ablation of Pdgfrα reporter+ cells resulted in significantly impaired calvarial bone healing. Our findings suggest that Pdgfrα-expressing cells within the calvarial niche play a critical role in the process of calvarial bone repair.

Early growth response factor 3 regulates coronary atherosclerosis through the NF-κB signaling pathway and VEGF expression.

AIM: The present study was conducted to measure the expression of early growth response factor 3 (Egr3), inflammatory cytokines (IL-1ß, IL-6), vascular endothelial growth factor (VEGF) and NF-κB in patients with coronary artery disease (CAD) to investigate the relationships of these molecules and Egr3 gene expression. METHODS: We recruited 132 CAD patients and 63 healthy individuals. The expression levels of Egr3, VEGF, p50 and p65 were measured by reverse transcription quantitative polymerase chain reaction and the levels of Egr3, IL-1ß and IL-6 in patients serum and in human coronary artery endothelial cells (HCAECs) were measured by enzyme-linked immunosorbent assay (ELISAs) in CAD patients. HCAECs were treated with ox-LDL to establish an in vitro atherosclerosis model. An oil red O staining assay was used to assess the lipid droplet formation. A colloidal external lumen formed by Matrigel was used to test the migration of HCAECs. The expression of Egr3, VEGF and NF-κB was determined by Western blotting. RESULTS: The levels of serum Egr3 and IL-6 in the severe stenosis group were greater than those in the mild stenosis group and controls (p < 0.05). The level of serum IL-1ß in the severe stenosis group was greater than that in the control group (p < 0.05). Moreover, Egr3 expression was positively associated with IL-6 levels (r= 0.55, p < 0.001), IL-1ß levels (r=0.21, p=0.004) and the Gensini score (r=0.20, p=0.02). We also found that Egr3 expression was significantly greater in CAD patients than that in controls. And its expression was highest in the mild patients. The expression of VEGF, P50 and P65 was also greater in CAD patients. In the in vitro experiment, we found that the inhibition of Egr3 expression significantly reduced the expression levels of p50, p65, IL-6 and CRP. Moreover, the inhibition of Egr3 expression significantly reduced the lipid droplet formation and decreased capability of lumen formation. CONCLUSIONS: In the pathogenesis of atherosclerosis, Egr3 gene expression may induce the expression of inflammatory factors and lipid droplet formation and lumen formation, which could promote the atherosclerosis development.

EXPERT OPINION REVIEW Utilizing somapacitan, a long-acting growth hormone formulation, for the treatment of adult growth hormone deficiency: a guide for the clinician.

OBJECTIVE: Somapacitan is the first approved and currently the only long-acting GH (LAGH) formulation in the United States for treatment of adults with growth hormone deficiency (GHD). The aim of this review was to provide a practical approach for clinicians on how to utilize somapacitan in the treatment of adults with GHD. METHODS: Literature search was performed on PubMed using key words, including adult growth hormone deficiency, long-acting growth hormone, somapacitan, treatment and management. The discussion of treatment aspects utilizing somapacitan was based on evidence from previous clinical studies and personal experience. RESULTS: Clinical trial data demonstrated that somapacitan, a once-weekly reversible albumin-binding GH derivative, decreased truncal fat, improved visceral fat and lean body mass, increased IGF-I standard deviation score and exerted neutral effects on glucose metabolism. Overall, somapacitan was well-tolerated, adverse event rates were comparable with daily GH, anti-somapacitan or anti-GH antibodies were not detected, and treatment satisfaction was in favor of somapacitan vs daily GH. CONCLUSION: Somapacitan is an efficacious, safe, convenient and well-tolerated once-weekly LAGH formulation that reduces the treatment burden of once-daily GH injections for adults with GHD. This article provides a review of the pharmacology of somapacitan and offers practical recommendations based on previous clinical trial data on how to initiate, dose titration, monitoring and dose adjustments whilst on therapy in adults with GHD. Timing of measurement of serum insulin-like growth factor-I levels, information on administration, recommendations on missed doses, and clinical recommendations on dosing in certain sub-population of patients are also discussed.

Role of hematological and neurological expressed 1 (HN1) in Human Cancers.

Hematological and neurological expressed 1 (HN1), also known as Jupiter microtubule associated homolog 1 (JPT1), is a highly conserved protein with widespread expression in various tissues. Ectopic elevation of HN1 has been observed in multiple cancers, highlighting its role in tumorigenesis and progression. Both proteomics and transcriptomics reveal that HN1 is closely associated with severe disease progression, poor prognostic and shorter overall survival. HN1's involvement in cancer cell proliferation and metastasis has been extensively investigated. Overexpression of HN1 is associated with increased tumor growth and disease progression, while its depletion leads to cell cycle arrest and apoptosis. The pivotal role of HN1 in cancer progression, particularly in proliferation, migration, and invasion, underscores its significance in cancer metastasis. Validation of the efficacy and safety of HN1 inhibition, along with the development of diagnostic methods to determine HN1 expression levels in patients, is essential for the translation of HN1-targeted therapies into clinical practice. Overall, HN1 emerges as a valuable prognostic marker and therapeutic target in cancer, and further investigations hold the potential to improve patient outcomes by impeding metastasis and enhancing treatment strategies.

Intracellular Signaling Pathways Involved in the Regulation of Gene Expression by Pilocarpine.

OBJECTIVES: Pilocarpine is commonly used clinically to treat dry mouth. The long-term administration of pilocarpine reportedly improves salivary secretion more effectively than short-term administration. Therefore, we hypothesized that pilocarpine alters gene expression in salivary glands via muscarinic receptor stimulation. This study aimed to investigate the effects of pilocarpine use on gene expression mediated by mitogen-activated protein kinase (MAPK) activity. METHODS: The effects of pilocarpine on gene expression were investigated in rats and human salivary gland (HSY) cells using several inhibitors of intracellular signaling pathways. Gene expression in the rat submandibular gland and HSY cells was determined using reverse transcription-quantitative polymerase chain reaction analysis of total RNA. RESULTS: In animal experiments, at 7 days after pilocarpine stimulation, Ctgf and Sgk1 expressions were increased in the submandibular gland. In cell culture experiments, pilocarpine increased Ctgf expression in HSY cells. The mitogen-activated protein kinase kinase inhibitor trametinib, the Src inhibitor PP2, and the muscarinic acetylcholine receptor antagonist atropine suppressed the effect of pilocarpine on gene expression. CONCLUSIONS: Pilocarpine enhances Ctgf and Sgk1 expressions by activating Src-mediated MAPK activity. Although further studies are required to fully understand the roles of Ctgf and Sgk1, changes in gene expression may play an important role in improving salivary secretions.

Detection of the GH analog somatrogon in sports drug testing: Immunological approaches and LC-HRMS/MS.

Due to the presumed lipolytic and anabolic properties, the misuse of human growth hormone (hGH) and its synthetic analogs in sports is prohibited both in- and out-of-competition. Within this research project, the detectability of somatrogon, a recombinant fusion glycoprotein of 22 kDa hGH and the C-terminal peptide (CTP) of the human chorionic gonadotropin (hCG) ß-subunit, with current WADA-approved doping control assays for hGH and hCG was investigated. For that purpose, cross-reactivity tests and a somatrogon administration study were conducted, and only "Kit 2" of the GH isoform differential immunoassays proved applicable to the detection of somatrogon administration in serum. In urine, the immunoassay specific for total hCG yielded presumptively positive findings for several post-administration samples, which can probably be attributed to the presence of an immunoreactive fragment of the hCG ß-subunit. As the detectability of somatrogon with these approaches was found to be limited, a highly specific detection assay (LOD: 10 ng/mL) for the drug in serum samples was developed by using affinity purification with GH receptor (GHR)-conjugated magnetic beads, proteolytic digestion, and liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS). Following optimization, the approach was comprehensively characterized, and authentic post-administration serum samples were successfully analyzed as proof-of-concept, indicating a detection window of at least 96 h. Consequently, the presented method can be employed to confirm the presence of somatrogon in serum samples, where only "Kit 2" of the currently used immunoassay kits yielded an abnormally high Rec/Pit ratio.

Human umbilical cord mesenchymal stem cells attenuate diabetic nephropathy through the IGF1R-CHK2-p53 signalling axis in male rats with type 2 diabetes mellitus. / 人脐带间å 质干细胞通过IGF1R-CHK2-p53信号轴减轻2åž‹ç³–å°¿ç— é›„æ€§å¤§é¼ ç³–å°¿ç— è‚¾ç— .

Diabetes mellitus (DM) is a disease syndrome characterized by chronic hyperglycaemia. A long-term high-glucose environment leads to reactive oxygen species (ROS) production and nuclear DNA damage. Human umbilical cord mesenchymal stem cell (HUcMSC) infusion induces significant antidiabetic effects in type 2 diabetes mellitus (T2DM) rats. Insulin-like growth factor 1 (IGF1) receptor (IGF1R) is important in promoting glucose metabolism in diabetes; however, the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear. In this study, a DM rat model was induced with high-fat diet feeding and streptozotocin (STZ) administration and rats were infused four times with HUcMSC. Blood glucose, interleukin-6 (IL-6), IL-10, glomerular basement membrane, and renal function were examined. Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays. The expression of IGF1R, phosphorylated checkpoint kinase 2 (p-CHK2), and phosphorylated protein 53 (p-p53) was examined using immunohistochemistry (IHC) and western blot analysis. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of 8-hydroxydeoxyguanosine (8-OHdG). Flow cytometry experiments were used to detect the surface markers of HUcMSC. The identification of the morphology and phenotype of HUcMSC was performed by way of oil red "O" staining and Alizarin red staining. DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane, increased the expression of IGF1 and IGF1R. IGF1R interacted with CHK2, and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells. When cisplatin was used to induce DNA damage, the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment. HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats. The expression of IGF1, IGF1R, p-CHK2, and p-p53, and the level of 8-OHdG in the DM group increased significantly compared with those in the control group, and decreased after HUcMSC treatment. Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage. HUcMSC infusion protected against kidney injury in DM rats. The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.

Association between risk of infant death and birth-weight z scores according to gestational age: A nationwide study using the Finnish Medical Birth Register.

OBJECTIVE: To investigate the association between infant mortality and birth weight using estimated fetal weight (EFW) versus birth-weight charts, by gestational age (GA). METHODS: This nationwide population-based study used data from the Finnish Medical Birth Register from 2006 to 2016 on non-malformed singleton live births at 24-41+6 weeks of gestation (N = 563 630). The outcome was death in the first year of life. Mortality risks by birth-weight z score, defined as a continuous variable using Marsál's EFW and Sankilampi's birth-weight charts, were assessed using generalized additive models by GA (24-27+6, 28-31+6, 32-36+6, 37-38+6, 39-41+6 weeks). We calculated z score thresholds associated with a two- and three-fold increased risk of infant death compared with newborns with a birth weight between 0 and 0.675 standard deviations. RESULTS: The z score thresholds (with corresponding centiles in parentheses) associated with a two-fold increase in infant mortality were: -3.43 (<0.1) at 24-27+6 weeks, -3.46 (<0.1) at 28-31+6 weeks, -1.29 (9.9) at 32-36+6 weeks, -1.18 (11.9) at 37-38+6 weeks, and - 1.34 (9.0) at 39-41+6 weeks according to the EFW chart. These values were - 2.43 (0.8), -2.62 (0.4), -1.34 (9.0), -1.37 (8.5), and - 1.43 (7.6) according to the birth-weight chart. CONCLUSION: The association between birth weight and infant mortality varies by GA whichever chart is used, suggesting that different thresholds for the screening of growth anomalies could be used across GA to identify high-risk newborns.

Left-behind cumulative risk and academic adjustment in Chinese middle school students: The moderating effect of growth mindset.

Left-behind children, as a large-scale disadvantaged group, encounter an array of risk factors that impede their academic development because of parental migration. The current study aimed at investigating the roles of left-behind cumulative risk and growth mindset on academic adjustment and exploring whether growth mindset moderated the association between left-behind cumulative risk and academic adjustment in left-behind middle school students. A total of 1184 left-behind middle school students (615 males; 12-16 years) participated in the study. Results indicated that left-behind cumulative risk is negatively associated with academic adjustment in middle school students (ß = -.199, t(1183) = -7.229, p < .001). Besides, growth mindset has a protective effect on left-behind middle school students' academic adjustment (ß = .386, t(1183) = 14.070, p < .001) and a moderating effect on the relationship between left-behind cumulative risk and academic adjustment (ß = .394, t(1182) = 4.057, p < .001, ΔR2 = .012). These findings suggest that family risk factors related to left-behind status affect the academic adjustment of left-behind middle school students in a superposition way, while the positive individual factor of growth mindset could protect the negative impact caused by parental migration.

Safety of embryo cryopreservation: insights from mid-term placental transcriptional changes.

BACKGROUND: In recent years, with benefits from the continuous improvement of clinical technology and the advantage of fertility preservation, the application of embryo cryopreservation has been growing rapidly worldwide. However, amidst this growth, concerns about its safety persist. Numerous studies have highlighted the elevated risk of perinatal complications linked to frozen embryo transfer (FET), such as large for gestational age (LGA) and hypertensive disorders during pregnancy. Thus, it is imperative to explore the potential risk of embryo cryopreservation and its related mechanisms. METHODS: Given the strict ethical constraints on clinical samples, we employed mouse models in this study. Three experimental groups were established: the naturally conceived (NC) group, the fresh embryo transfer (Fresh-ET) group, and the FET group. Blastocyst formation rates and implantation rates were calculated post-embryo cryopreservation. The impact of FET on fetal growth was evaluated upon fetal and placental weight. Placental RNA-seq was conducted, encompassing comprehensive analyses of various comparisons (Fresh-ET vs. NC, FET vs. NC, and FET vs. Fresh-ET). RESULTS: Reduced rates of blastocyst formation and implantation were observed post-embryo cryopreservation. Fresh-ET resulted in a significant decrease in fetal weight compared to NC group, whereas FET reversed this decline. RNA-seq analysis indicated that the majority of the expression changes in FET were inherited from Fresh-ET, and alterations solely attributed to embryo cryopreservation were moderate. Unexpectedly, certain genes that showed alterations in Fresh-ET tended to be restored in FET. Further analysis suggested that this regression may underlie the improvement of fetal growth restriction in FET. The expression of imprinted genes was disrupted in both FET and Fresh-ET groups. CONCLUSION: Based on our experimental data on mouse models, the impact of embryo cryopreservation is less pronounced than other in vitro manipulations in Fresh-ET. However, the impairment of the embryonic developmental potential and the gene alterations in placenta still suggested it to be a risky operation.

Assessing the Influence of Guanidinoacetic Acid on Growth Performance, Body Temperature, Blood Metabolites, and Intestinal Morphometry in Broilers: A Comparative Sex-Based Experiment.

It is well known that female and male broilers showcase variations in their growth performance, influenced by various physiological factors. This experiment aims to explore potential differences between female and male broilers concerning growth performance, body temperature, blood metabolites, carcass traits, and intestinal architecture in response to guanidinoacetic acid (GAA) supplementation. A total of 240 Ross 308 broiler chickens were arranged in a 3 × 2 factorial design and randomly allocated into 48 boxes, each containing 5 birds. The experiment comprised six treatments, with eight replicates per treatment. The main factors investigated were dietary GAA levels (0%, 0.06%, and 0.12%) and sex (male and female). Male broilers demonstrated superior body weight gain (BWG) and feed intake (FI) compared to females (p< 0.05). GAA supplementation at 0.12% concentration notably improved BWG and reduced FI and feed conversion ratio (FCR) across experimental phases (p < 0.05). However, interactions between sex and GAA were minimal except for reduced FI and FCR (p < 0.05) in both sexes during early growth stages. Regardless of GAA treatment, the male birds exhibited more elevated shank and head temperatures than the females. Carcass traits were largely unaffected by GAA supplementation or sex, except for higher heart yield in the males. Serum metabolite levels were not different between treatment groups at 10 and 24 days of age, except for a higher level of serum creatinine at 10 days in the female birds with 0.06% GA supplementation (p < 0.05). Intestinal morphology was significantly affected by GAA and sex, depending on the segment of intestine, in which GAA supplementation significantly increased villus height, crypt depth, villus width, surface area, and goblet cell count, while the males consistently exhibited higher values of these parameters than the females, and differences were observed between intestinal segments, especially in the ileum and duodenum, at different ages. In conclusion, the interactions between GAA and sex had minimal influences on growth performance indices. However, male broilers demonstrated a more pronounced response to GAA concerning ileal architecture. This study highlights the importance of supplementing broiler chicken diets with GAA for optimizing male broiler performance and intestinal function. The inclusion of GAA into broiler diets needs further study to reveal the underlying mechanisms driving these sex-specific responses and assess the long-term impacts of GAA supplementation on broiler health and productivity.

Animal Behaviour Packs a Punch: From Parasitism to Production, Pollution and Prevention in Grazing Livestock.

Behaviour is often the fundamental driver of disease transmission, where behaviours of individuals can be seen to scale up to epidemiological patterns seen at the population level. Here we focus on animal behaviour, and its role in parasite transmission to track its knock-on consequences for parasitism, production and pollution. Livestock face a nutrition versus parasitism trade-off in grazing environments where faeces creates both a nutritional benefit, fertilizing the surrounding sward, but also a parasite risk from infective nematode larvae contaminating the sward. The grazing decisions of ruminants depend on the perceived costs and benefits of the trade-off, which depend on the variations in both environmental (e.g., amounts of faeces) and animal factors (e.g., physiological state). Such grazing decisions determine the intake of both nutrients and parasites, affecting livestock growth rates and production efficiency. This impacts on the greenhouse gas costs of ruminant livestock production via two main mechanisms: (1) slower growth results in longer durations on-farm and (2) parasitised animals produce more methane per unit food intake. However, the sensitivity of behaviour to host parasite state offers opportunities for early detection of parasitism and control. Remote monitoring technology such as accelerometers can detect parasite-induced sickness behaviours soon after exposure, before impacts on growth, and thus may be used for targeting individuals for early treatment. We conclude that livestock host x parasite interactions are at the centre of the global challenges of food security and climate change, and that understanding livestock behaviour can contribute to solving both.

Influence of Replacing Soybean Meal with Nigella sativa Seed Meal on Feed Intake, Digestibility, Growth Performance, Blood Metabolites, and Antioxidant Activity of Growing Lambs.

The present experiment aimed to evaluate the partial or complete substitution of soybean meal (SBM) with Nigella sativa seed meal (NSM) on chemical composition, in vitro ruminal fermentation, and the growth performance and economic efficiency of growing lambs. Thirty-two male Ossimi lambs weighing 41 ± 0.4 kg at 195 ± 5 d were divided randomly into four experimental groups of eight lambs each. Lambs were fed four diets containing 40% berseem clover and 60% concentrate feed mixture. Soybean meal was replaced with NSM at 0% (NSM0; control), 50% (NSM50), 75% (NSM75), or 100% (NSM100). The experiment lasted for 105 d, consisting of 15 d for adaptation and 90 days for measurements. Higher concentrations of crude protein (CP) and nonstructural carbohydrates were observed with SBM; however, NSM contained more fibers and gross energy. Moreover, SBM contained higher concentrations of individual amino acids and lower concentrations of polyphenols. The replacement did not affect in vitro gas production and decreased (p < 0.05) methane production and CP degradability. Treatments did not affect feed intake, nutrient digestibility, and diet's nutritive value measured as starch value, total digestible nutrient, digestible energy, and apparent digestible crude protein. The NSM50 and NSM75 treatments increased (p < 0.001) total weight gain and daily gain compared to the control treatment, with lower feed conversion values associated with the NSM75 treatment. Treatments decreased cholesterol (p = 0.028) and high-density lipoprotein (p = 0.029) and increased antioxidant activity. Higher economic efficiencies were observed with the NSM75 followed by NSM50 and then NSM100 treatments. It is concluded that replacing 75% of SBM with NSM enhanced feed conversion and economic efficiency.

Effects of Micellar Quercetin Supplementation on Growth Performance, Nutrient Digestibility, Fecal Microbiota, Meat Quality, and Physiological Status in Broiler Chickens.

This study investigated the impacts of micellar quercetin (MQ) supplementation on growth performance, meat stability, excreta gas emissions, and physiological status. During a 35-day trial, 640 Ross 308 broilers were utilized. These birds were one day old, with an average initial body weight of 43.34 ± 1.43 g. They were randomly distributed across four experimental diets, each consisting of 10 replicate pens with 16 chicks per pen. The diets included the following: control (CON) with 0% micellar quercetin (MQ), TRT1 with 0.025% MQ, TRT2 with 0.050% MQ, and TRT3 with 0.100% MQ. The results indicate that broilers fed diets with increasing levels of MQ exhibited significantly higher body weight gains (BWGs) compared to the control group (p < 0.05). There was a clear linear increase in the breast muscle percentage with higher levels of quercetin supplementation (p < 0.05), while the breast color remained consistent across all groups (p > 0.05). Both cooking loss and drip loss exhibited a linear decrease as MQ levels in the diet increased (p < 0.05). The level of aspartate aminotransferase (AST) tended to decrease with higher MQ levels. Thyroxine (T4) and lymphocyte levels also showed a linear increase with increasing MQ dosage in the diet (p < 0.05). However, no significant effects were observed on nutrient digestibility, gas emissions, or fecal microbial components (Lactobacillus, E. coli, and Salmonella) with higher levels of MQ supplementation (p > 0.05). In conclusion, augmenting quercetin levels in the diet positively influenced the BWG, breast muscle development, and meat quality parameters such as cooking loss and drip loss, with beneficial effects on blood profiles.

Sucralose Influences the Productive Performance, Carcass Traits, Blood Components, and Gut Microflora Using 16S rRNA Sequencing of Growing APRI-Line Rabbits.

This study investigated how sucralose influenced rabbit intestine and caecal microbial activity, blood parameters, growth performance, carcass characteristics, and digestibility. In total, 160 5-week-old rabbits from the APRI line weighing 563.29 gm were randomly assigned to four experimental groups with four replicates-5 males and 5 females in each. Four experimental groups were used, as follows: SUC1, SUC2, and SUC3 got 75, 150, and 300 mg of sucralose/kg body weight in water daily, while the control group ate a basal diet without supplements. The results showed that both the control and SUC1 groups significantly (p < 0.05) increased daily weight gain and final body weight. Sucralose addition significantly improved feed conversion ratio (p < 0.05) and decreased daily feed intake (gm/d). The experimental groups do not significantly differ in terms of mortality. Furthermore, nutrient digestibility was not significantly affected by sucralose treatment, with the exception of crud protein digestion, which was significantly reduced (p < 0.05). Additionally, without altering liver or kidney function, sucralose administration dramatically (p < 0.05) decreased blood serum glucose and triglyceride levels while increasing total lipids, cholesterol, and malonaldehyde in comparison to the control group. Furthermore, the addition of sucrose resulted in a significant (p < 0.05) increase in the count of total bacteria, lactobacillus, and Clostridium spp., and a decrease in the count of Escherichia coli. Further analysis using 16S rRNA data revealed that sucralose upregulated the expression of lactobacillus genes but not that of Clostridium or E. Coli bacteria (p < 0.05). Therefore, it could be concluded that sucralose supplementation for rabbits modifies gut microbiota and boosts beneficial bacteria and feed conversion ratios without side effects. Moreover, sucralose could decrease blood glucose and intensify hypercholesterolemia and should be used with caution for human consumption.

Organic Iodine Improves the Growth Performance and Gut Health of Fujian Yellow Rabbits.

Organic iodine is a new trace element additive that is highly efficient in regulating cell growth, function, and metabolism. This study demonstrated that organic iodine improves the growth performance and gut health of Fujian yellow rabbits. A total of 160 healthy rabbits of similar weight were randomly divided into four groups, which were treated with organic iodine (0, 0.5, 1.0, and 1.5 mg/kg) for 60 days. Our results indicated that organic iodine improved the growth performance, including significantly increased BW, ADG, and ADFI, and decreased F/G notably. Organic iodine improved the content of T3, T4, IgM, IgA, and IgM in serum, and intestinal mucosal immunity (IL-1α, IL-2, and sIgA). Organic iodine supplementation ameliorated gut morphometry and morphology, such as higher villus height and lower crypt depth. Organic iodine increased the amount of goblet cells significantly. The 0.5 mg/kg organic iodine most increased the activities of amylase, cellulase, and trypsin in caecum. Organic iodine induced more active caecum fermentation, higher NH3-N, acetic acid, propionic acid, and butyric acid, while lowering PH. In conclusion, organic iodine improved the growth performance and gut morphometry and morphology, and increased caecum enzyme activities, active caecum fermentation, and intestinal immunity of Fujian yellow rabbits.

Exploring the Effect of Gastrointestinal Prevotella on Growth Performance Traits in Livestock Animals.

Microorganisms in the rumen play a crucial role in determining the most efficient utilization rate of nutrients. Among these microorganisms, Prevotella stands out as one of the most representative bacteria within the rumen biological system. Prevotella is a common strict anaerobic bacterium that is found in the gastrointestinal tract of livestock. Prevotella plays a crucial role in breaking down and metabolizing complex nutrients like cellulose and protein during food digestion. Moreover, it is capable of working together with other bacteria in the body's digestive system. Several studies have shown a strong correlation between the abundance of Prevotella and livestock growth performance. This paper provides a comprehensive review of the current research on the function, mechanisms, and applications of Prevotella in the gastrointestinal tract. The insights provided in this review could serve as a theoretical basis for accurately classifying Prevotella, further investigating its effects and potential mechanisms on livestock growth performance, and exploring its practical applications.