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The objective of the present study was to investigate the effect of in ovo injection of a - galactosides on the development of the intestinal villi in the small intestine of broiler chickens. In order to verify the objective 80 000 eggs were divided into two groups, the control and the experimental; 40 000 eggs in each. Solution containing a - galactosides were injected in ovo into the air cell on the 12th d of embryonic development. At the age of 0 (DOH), 4, 7 and 14 days 10 animals of each group were randomly selected and slaughtered, and the intestine samples were collected for histological examinations. Results show that the single injection of a - galactosides has a beneficial effect on morphometrical and histological parameters of intestine. In our study we observed that the each segments of small intestine and consequently the total length of the intestine was significantly higher (P ≤ 0.05) in the experimental group at day of hatch. Furthermore, the results showed stimulatory effect of the a - galactosides on height of the villi, surface area and crypt depth in all studied segments of the intestine in the in ovo experimental group (P ≤ 0.05) at day of hatch. The observed effect of injection on studied parameters wasn't permanent and remained for 3 days after hatching. [ABSTRACT FROM AUTHOR]

Background: Application the innovative method which is in ovo technology provides a means of modulating the immune system at early embryonic stages. The aim of study was to determine influence of the in ovo stimulation, on d 12 of incubation, with synbiotics (synbiotic 1-L. salivarius IBB3154 + Bi2tos, Clasado Ltd. and the synbiotic 2-L. plantarum IBB3036 + lupin RFOs) on the microstructure of duodenum, jejunum and ileum in the 1st and 42nd day of rearing. Results: On the 1st day of chickens life, in the duodenum of both experimental groups (SYN1 and SYN2), a significantly higher and wider intestinal villi as well as a significantly larger absorbent surface of these villi were found in comparison with the Control group (P ≤ 0.01). On the 42nd day of rearing the beneficial effect of synbiotic 1 was reflected by the numerically higher villi (no statistical differences) with a larger surface (P ≤ 0.01) in the duodenum in the SYN1 group compare to the Control group. In the jejunum on the 1st day of life, in the SYN1 group, significantly higher villi than in the Control group, with a simultaneous decrease in the depth of crypts (P ≤ 0.01) and also the largest width of villi and their absorbent area (P ≤ 0.01) in comparison to the other groups were found. On the 42nd day of life, in the jejunum, an increase in the height of the villi whilst reducing the crypt depth in the SYN2 group was found (P ≤ 0.01). In turn, in the SYN1 group, there were significantly more neutral goblet cells observed compared with the control group (P ≤ 0.05). In the ileum of 1-day-old chickens, the widest villi (P ≤ 0.05) and the deepest crypts (P ≤ 0.01) were found in the SYN2 group. In the same group, there was also the least amount of neutral goblet cells in comparison to the other groups (P ≤ 0.05). Conclusions: We observed that synbiotic 1 and 2 beneficially affected the examined characteristics on the 1st and 42nd day of life. The obtained results allow us to conclude that the use of synbiotics significantly affect gut structure which should contribute to improvement in nutrient absorption by the gut. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the effect of the injection of raffinose-family oligosaccharides during embryogenesis on the rate of resorption of the yolk sac. 80 000 eggs were divided in two groups, the control and the experimental; 40 000 eggs in each. The experimental group eggs were injected on the 12th day of hatch directly into the air cell with the substance containing a-galactosides. The yolk sac's were sampled right after slaughter from earlier weighed, 1, 4, 7 and 14-day chickens, from 10 broilers each time. In the investigation the parameters of yolk sac were e.g. yolk sac/body weight ratio and the egg yolk absorption. Moreover, there was also evaluated mean body weight, feed conversion ratio, mortality rate and the European Efficiency Ratio. Results showed that the single injection have a favourable effect on yolk sac resorption rate. Yolk sac/body weight ratio decreased and the estimated yolk absorption increase in experimental group. Also better indicators of production were found in the experimental group. [ABSTRACT FROM AUTHOR]

Porcine chromosome 4 harbours many quantitative trait loci (QTL) affecting meat quality, fatness and carcass composition traits, detected in resource pig populations previously. However, prior to selection in commercial breeds, QTL identified in an intercross between divergent breeds require confirmation, so that they can be segregated. Consequently, the objective of this study was to validate several QTL on porcine chromosome 4 responsible for meat and carcass quality traits. The experimental population consisted of 14 crossbred paternal half-sib families. The region of investigation was the q arm of SSC4 flanked by the markers S0073 and S0813. Regression analysis resulted in the validation of three QTL within the interval: Minolta a* loin, back fat thickness and the weight of trimmed ham. The results were additionally confirmed by factor analysis. Candidate genes were proposed for meat colour, which was the most evident QTL validated in this study. [ABSTRACT FROM AUTHOR]

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The objective of this research was to determine the optimal level of an encapsulated butyric acid (ButiPEARL) based on the performance of male Cobb broilers reared to 42 d of age and to investigate its effects on intestinal morphology. Experiment 1 (EXP 1) consisted of 4 treatments with 12 replicate pens that contained 45 broilers, and Experiment 2 (EXP 2) consisted of 6 treatments with 8 replicate pens that contained 50 broilers. Birds were weighed by pen on d 0, 21, 35, and 42. In EXP 1, the treatments were as follows: 1) control (C); 2) C + 100 g Buti- PEARL/ton; 3) C + 200 g ButiPEARL/ton; and 4) C + 300 g ButiPEARL/ton. In EXP 2, the treatments were identical to EXP 1, with 2 additional treatments: 5) C + 400 g ButiPEARL/ton and 6) C + 500 g Buti- PEARL/ton. In EXP 1, two 42-d-old broilers per pen were randomly selected for duodenal and jejunal tissue collection. Only the samples from the broilers fed the C or 300 g ButiPEARL treatments were analyzed for histology in EXP 1. For EXP 2, on d 21 and 35, two broilers per pen were randomly selected for duodenal, jejunal, and ileal tissue collection. For EXP 1 and 2, BW gain increased linearly with increasing butyric acid levels (P < 0.027 and P < 0.001, respectively). For EXP 1 and 2, feed conversion linearly improved with increasing butyric acid from 0 to 42 d (P < 0.001 and P < 0.001, respectively). In EXP 1, there were no differences in any intestinal morphology at 42 d between broilers fed the C or 300 g ButiPEARL treatments. In EXP 2, there were no differences in villus height at 21 or 35 d of age with any level of butyric acid. Based on the results of this research related to BW gain and feed conversion, the recommended optimum dosage level for ButiPEARL in broilers reared to 42 d of age is up to 500 g/ton. [ABSTRACT FROM AUTHOR]

Obesity is one of the world's major public health challenges. Its pathogenesis and comorbid metabolic disorders share common mechanisms, such as mitochondrial or endoplasmic reticulum dysfunction or oxidative stress, gut dysbiosis, chronic inflammation and altered autophagy. Numerous pro-autophagy dietary interventions are being investigated for their potential obesity-preventing or therapeutic effects. We summarize current data on the relationship between autophagy and obesity, and discuss various dietary interventions as regulators of autophagy-related genes in the prevention and ultimate treatment of obesity in humans, as available in scientific databases and published through July 2024. Lifestyle modifications (such as calorie restriction, intermittent fasting, physical exercise), including following a diet rich in flavonoids, antioxidants, specific fatty acids, specific amino acids and others, have shown a beneficial role in the induction of this process. The activation of autophagy through various nutritional interventions tends to elicit a consistent response, characterized by the induction of certain kinases (including AMPK, IKK, JNK1, TAK1, ULK1, and VPS34) or the suppression of others (like mTORC1), the deacetylation of proteins, and the alleviation of inhibitory interactions between BECN1 and members of the Bcl-2 family. Significant health/translational properties of many nutrients (nutraceuticals) can affect chronic disease risk through various mechanisms that include the activation or inhibition of autophagy. The role of nutritional intervention in the regulation of autophagy in obesity and its comorbidities is not yet clear, especially in obese individuals.

Purpose: The aim of this study was to compare surgical and sexual outcomes after Davidov-Moore vaginoplasty in women with Mayer-Rokitansky-Küster-Hauser syndrome (MRKH)., Methods: In the case-series study, we described seven women, at a median age of 22.6 ± and BMI 22.8 ± 2.3 kg/m 2 . We measured peri- and postsurgical parameters, including surgery-related neovaginal length and sexual initiation time. Sexual outcomes were measured using the Female Sexual Function Index (FSFI) before and 6 months after vaginoplasty., Results: All surgical procedures were performed successfully, with one minor perioperative bleeding. The mean time of vaginoplasty was 82.1 min and the mean duration of hospitalization was six days. After a 6-month follow-up, vaginal length was 8.1-times longer than before surgery (10 vs. 81 mm). The time from the surgery to the initiation of vaginal intercourse was between 17 to 22 weeks. The mean FSFI score indicated good results, with no women below 23 score, and was 4.3- times higher when compared with the pre-surgical one (6.7 vs 29.1). Contrary to the FSFI score before surgery, the post-surgical FSFI revealed higher scores in all six different domains: desire (2.5-times), arousal (4.1-times), lubrication (3.8-times), orgasm (3.4-times), satisfaction (3.3-times) and comfort (11-times)., Conclusion: Laparoscopic Davydov-Moore vaginoplasty might be considered as a safe procedure with satisfactory anatomic and sexual outcomes. It should be considered as a treatment option for the creation of neovagina in women with MRKH., Competing Interests: Declarations Conflict of interest None., (© 2024. The Author(s).)

The recent COVID-19 pandemics have demonstrated the great therapeutic potential of in vitro transcribed (IVT) mRNAs, but improvements in their biochemical properties, such as cellular stability, reactogenicity and translational activity, are critical for further practical applications in gene replacement therapy and anticancer immunotherapy. One of the strategies to overcome these limitations is the chemical modification of a unique mRNA 5'-end structure, the 5'-cap, which is responsible for regulating translation at multiple levels. This could be achieved by priming the in vitro transcription reaction with synthetic cap analogs. In this study, we combined a highly efficient trinucleotide IVT capping technology with several modifications of the 5' cap triphosphate bridge to synthesize a series of 16 new cap analogs. We also combined these modifications with epigenetic marks (2'-O-methylation and m6Am) characteristic of mRNA 5'-ends in higher eukaryotes, which was not possible with dinucleotide caps. All analogs were compared for their effect on the interactions with eIF4E protein, IVT priming, susceptibility to decapping, and mRNA translation efficiency in model cell lines. The most promising α-phosphorothiolate modification was also evaluated in an in vivo mouse model. Unexpected differences between some of the analogs were analyzed using a protein cell extract pull-down assay., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Angelman syndrome (AS) is a rare neurodevelopmental disease caused by imprinting disorders that impede the production of the ubiquitin E3A ligase protein (UBE3A). AS affects multiple systems, with the main symptoms including epilepsy, psychomotor disorders and speech development disorders. To date, no study has been conducted in the Polish population to verify the condition's diagnosis and treatment process., Results: Seventy patients with the median age of 60 months were included into the analysis. 80% of patients were diagnosed with deletion, 19.9% with a mutation of UBE3A gene, 4.3% with paternal uniparental disomy (UPD) and 2.8% with an imprinting defect. The mean age of first symptoms was 5 months, while the mean age of diagnosis was 29 months (earliest in deletion group at 23 months), and the median duration of diagnosis process was 7 months. The average time to a clinical geneticist appointment was 3 months. 37.9% of the patients initially received a different diagnosis. Epileptic seizures were present in 88.6% of the individuals. 98.6% of the studied group were under care of a pediatric neurologist, 47.1% of a gastroenterologist. A ketogenic diet was used in 7.1% of patients. Caregivers identified finding a specialist suitable for AS patients and access to genetic testing as the biggest problems., Conclusions: The care of patients with AS in Poland is carried out according to the European and world standards, however there is an impeded access to clinical geneticist, and the knowledge about rare diseases among primary healthcare physicians could be improved. Moreover, access to AS care specialists and coordination of care is limited. There is a need for creation a specialized centers and databases for AS patients., (© 2024. The Author(s).)

This paper presents an energy-efficient and high-accuracy sampling synchronization approach for real-time synchronous data acquisition in wireless sensor networks (saWSNs). A proprietary protocol based on time-division multiple access (TDMA) and deep energy-efficient coding in sensor firmware is proposed. A real saWSN model based on 2.4 GHz nRF52832 system-on-chip (SoC) sensors was designed and experimentally tested. The obtained results confirmed significant improvements in data synchronization accuracy (even by several times) and power consumption (even by a hundred times) compared to other recently reported studies. The results demonstrated a sampling synchronization accuracy of 0.8 μs and ultra-low power consumption of 15 μW per 1 kb/s throughput for data. The protocol was well designed, stable, and importantly, lightweight. The complexity and computational performance of the proposed scheme were small. The CPU load for the proposed solution was <2% for a sampling event handler below 200 Hz. Furthermore, the transmission reliability was high with a packet error rate (PER) not exceeding 0.18% for TXPWR ≥ -4 dBm and 0.03% for TXPWR ≥ 3 dBm. The efficiency of the proposed protocol was compared with other solutions presented in the manuscript. While the number of new proposals is large, the technical advantage of our solution is significant.

Primordial germ cells (PGCs) are the precursors of functional gametes and the only cell type capable of transmitting genetic and epigenetic information from generation to generation. These cells offer valuable starting material for cell-based genetic engineering and genetic preservation, as well as epigenetic studies. While chicken PGCs have demonstrated resilience in maintaining their germness characteristics during both culturing and cryopreservation, their handling remains a complex challenge requiring further refinement. Herein, the study aimed to compare the effects of different conditions (freezing-thawing and in vitro cultivation) on the expression of PGC-specific marker genes. Embryonic blood containing circulating PGCs was isolated from purebred Green-legged Partridgelike chicken embryos at 14-16 Hamburger-Hamilton (HH) embryonic development stage. The blood was pooled separately for males and females following sex determination. The conditions applied to the blood containing PGCs were as follows: (1) fresh isolation; (2) cryopreservation for a short term (2 days); and (3) in vitro culture (3 months) with long-term cryopreservation of purified PGCs (~2 years). To characterize PGCs, RNA isolation was carried out, followed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) to assess the expression levels of specific germ cell markers ( SSEA1 , CVH , and DAZL ), as well as pluripotency markers ( OCT4 and NANOG ). The investigated genes exhibited consistent expression among PGCs maintained under diverse conditions, with no discernible differences observed between males and females. Notably, the analyzed markers demonstrated higher expression levels in PGCs when subjected to freezing than in their freshly isolated counterparts.

Eukaryotic mRNAs undergo cotranscriptional 5'-end modification with a 7-methylguanosine cap. In higher eukaryotes, the cap carries additional methylations, such as m6 A m ─a common epitranscriptomic mark unique to the mRNA 5'-end. This modification is regulated by the Pcif1 methyltransferase and the FTO demethylase, but its biological function is still unknown. Here, we designed and synthesized a trinucleotide FTO-resistant N 6-benzyl analogue of the m6 A m -cap-m 7 Gppp Bn6 A m pG (termed AvantCap ) and incorporated it into mRNA using T7 polymerase. mRNAs carrying Bn6 A m showed several advantages over typical capped transcripts. The Bn6 A m moiety was shown to act as a reversed-phase high-performance liquid chromatography (RP-HPLC) purification handle, allowing the separation of capped and uncapped RNA species, and to produce transcripts with lower dsRNA content than reference caps. In some cultured cells, Bn6 A m mRNAs provided higher protein yields than mRNAs carrying A m or m6 A m , although the effect was cell-line-dependent. m 7 Gppp Bn6 A m pG-capped mRNAs encoding reporter proteins administered intravenously to mice provided up to 6-fold higher protein outputs than reference mRNAs, while mRNAs encoding tumor antigens showed superior activity in therapeutic settings as anticancer vaccines. The biochemical characterization suggests several phenomena potentially underlying the biological properties of AvantCap : (i) reduced propensity for unspecific interactions, (ii) involvement in alternative translation initiation, and (iii) subtle differences in mRNA impurity profiles or a combination of these effects. AvantCapped- mRNAs bearing the Bn6 A m may pave the way for more potent mRNA-based vaccines and therapeutics and serve as molecular tools to unravel the role of m6 A m in mRNA.

Background: Dysregulation of the autophagy process via ubiquitin is associated with the occurrence of a number of diseases, including cancer. The present study analyzed the changes in the transcriptional activity of autophagy-related genes and the ubiquitination process (UPS) in colorectal cancer tissue. (2) Methods: The process of measuring the transcriptional activity of autophagy-related genes was analyzed by comparing colorectal cancer samples from four clinical stages I-IV (CS I-IV) of adenocarcinoma to the control (C). The transcriptional activity of genes associated with the UPS pathway was determined via the microarray technique (HG-U133A, Affymetrix). (3) Results: Of the selected genes, only PTEN-induced kinase 1 (PINK1) indicated statistical significance for all groups of colon cancer tissue transcriptome compared to the control. The transcriptional activity of the protein tyrosine phosphatase non-receptor type 22 (PTPN22 ) gene increased in all stages of the cancer, but the p -value was only less than 0.05 in CSIV vs. C. Forkhead box O1 (FOXO 1 ) and ubiquitin B (UBB) are statistically overexpressed in CSI. (4) Conclusions: The pathological expression changes in the studied proteins observed especially in the early stages of colorectal cancer suggest that the dysregulation of ubiquitination and autophagy processes occur during early neoplastic transformation. Stopping or slowing down the processes of removal of damaged proteins and their accumulation may contribute to tumor progression and poor prognosis.

Introduction: Multiple myeloma is a B-cell malignancy caused by proliferating plasma cells in the bone marrow microenvironment in collaboration with various cell lineage subsets and growth factors without any perfect regulation and tendency to clonal heterogeneity. Despite remarkable improvement in MM treatment and the overall survival of patients, multiple myeloma remains an incurable disease with the tendency to relapse. Therefore, there is an urgent need for new therapeutic options to provide a stabilized response to treatment with long-term duration., Areas Covered: Elranatamab (PF-06863135), is a novel heterodimeric humanized full-length bispecific IgG2 kappa antibody derived from 2 mAbs, the anti-BCMA mAb (PF-06863058) and the anti-CD3 mAb (PF-06863059), not yet licensed in routine use. This binding affinity of elranatamab to BCMA and CD3 has been optimized to potentially prompt more potent T cell-mediated anti-myeloma activity. Subcutaneous (s.c.) administration of elranatamab is superior in comparison to intravenous (i.v.), thus it is associated with lower incidence of adverse events, even in higher doses., Expert Opinion: Currently, elranatamab is being investigated in a few clinical studies, and the preliminary results are very encouraging. At the time of writing this review there were no full papers published and all of the data in the literature were based on abstract presentations which carry limitations.

The present study aimed to test the synbiotic PoultryStar ® sol US delivered in ovo to evaluate its effect on hatchability, productive performance and meat quality, compared to its post-hatch administration in water. On the twelfth day of embryonic incubation, 1200 fertile eggs were divided into synbiotic groups injected with 2 mg/embryo (T1) and 3 mg/embryo (T2), a saline group injected with physiological saline and an uninjected control group (C). After hatching, 120 male chicks/group were reared and chicks from the saline group were supplemented with the synbiotic via drinking water (T3). Hatchability was low in both T1 and T2 groups. Growth performance was not affected by the treatments. However, in the second rearing phase (15-36 days), birds from the C and T3 groups were heavier than T1 birds, due to a higher feed intake and daily weight gain. Neither route of synbiotic administration influenced final body weight (at 56 days), weight and yield of the carcass or commercial cuts. Physico-chemical properties, total lipid, cholesterol and fatty acid composition of breast muscle were not affected by the treatments. Considering its exploratory nature, this study has raised many questions that need further investigation, such as the bioactive combination and the effect on embryonic development., Competing Interests: The authors declare no conflict of interest.

Chemical modifications of the mRNA cap structure can enhance the stability, translational properties, and half-life of mRNAs, thereby altering the therapeutic properties of synthetic mRNA. However, cap structure modification is challenging because of the instability of the 5'-5'-triphosphate bridge and N7-methylguanosine. The Suzuki-Miyaura cross-coupling reaction between boronic acid and halogen compound is a mild, convenient, and potentially applicable approach for modifying biomolecules. Herein, we describe two methods to synthesize C8-modified cap structures using the Suzuki-Miyaura cross-coupling reaction. Both methods employed phosphorimidazolide chemistry to form the 5',5'-triphosphate bridge. However, in the first method, the introduction of the modification via the Suzuki-Miyaura cross-coupling reaction at the C8 position occurs postsynthetically, at the dinucleotide level, whereas in the second method, the modification was introduced at the level of the nucleoside 5'-monophosphate, and later, the triphosphate bridge was formed. Both methods were successfully applied to incorporate six different groups (methyl, cyclopropyl, phenyl, 4-dimethylaminophenyl, 4-cyanophenyl, and 1-pyrene) into either the m 7 G or G moieties of the cap structure. Aromatic substituents at the C8-position of guanosine form a push-pull system that exhibits environment-sensitive fluorescence. We demonstrated that this phenomenon can be harnessed to study the interaction with cap-binding proteins, e.g. , eIF4E, DcpS, Nudt16, and snurportin.