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Protein-protein interaction network analysis revealed that translational and ribosomal quality control proteins were significant regulators in the P23H rhodopsin protein interactome. The protein partners identified in our study may provide new insights into how photoreceptors recognize and clear mutant rhodopsin, offering possible novel targets involved in retinal degeneration pathogenesis.This study aimed to assess the association between interpregnancy interval (IPI)-the time from childbirth to conception of the next pregnancy-and maternal and neonatal morbidity. The World Health Organization (WHO) currently recommends an IPI of at least 24 months after a live birth to reduce adverse birth outcomes. However, assessing the relationship between IPI and perinatal outcome is complicated by confounding factors. We conducted a nationwide population-based cohort study using Swedish registry data, allowing for adjustment of maternal characteristics and health at first birth. The study population consisted of all women with a singleton, live, and vaginal first birth with a second singleton birth within five years during 1997-2017, covering 327,912 women and 655,824 neonates. IPI was grouped into six-month intervals with 24-29 months as the reference. The association between IPI and morbidity was examined using multivariate logistic regression. For women having a vaginal delivery at their first birth, intervals  24-29 months were associated with increased maternal and neonatal morbidity. Our findings question the relevance of WHO's recommendation of an IPI of at least 24 months in a high-income country.Complex genetic predispositions accelerate the chronic degeneration of midbrain substantia nigra neurons in Parkinson's disease (PD). Deciphering the human molecular makeup of PD pathophysiology can guide the discovery of therapeutics to slow the disease progression. However, insights from human postmortem brain studies only portray the latter stages of PD, and there is a lack of data surrounding molecular events preceding the neuronal loss in patients. We address this gap by identifying the gene dysregulation of live midbrain neurons reprogrammed in vitro from the skin cells of 42 individuals, including sporadic and familial PD patients and matched healthy controls. To minimize bias resulting from neuronal reprogramming and RNA-seq methods, we developed an analysis pipeline integrating PD transcriptomes from different RNA-seq datasets (unsorted and sorted bulk vs. single-cell and Patch-seq) and reprogramming strategies (induced pluripotency vs. direct conversion). This PD cohort's transcriptome is enriched for human genes associated with known clinical phenotypes of PD, regulation of locomotion, bradykinesia and rigidity. Dysregulated gene expression emerges strongest in pathways underlying synaptic transmission, metabolism, intracellular trafficking, neural morphogenesis and cellular stress/immune responses. We confirmed a synaptic impairment with patch-clamping and identified pesticides and endoplasmic reticulum stressors as the most significant gene-chemical interactions in PD. MRTX0902 in vitro Subsequently, we associated the PD transcriptomic profile with candidate pharmaceuticals in a large database and a registry of current clinical trials. This study highlights human transcriptomic pathways that can be targeted therapeutically before the irreversible neuronal loss. Furthermore, it demonstrates the preclinical relevance of unbiased large transcriptomic assays of reprogrammed patient neurons.Human immunodeficiency virus type 1 (HIV-1)-based lentiviral vectors are indispensable tools for gene engineering in mammalian cells. Conversely, lentiviral vector transduction is severely inhibited in bovine cells. Previous studies demonstrated that this inhibition is caused by the anti-lentiviral host factor tripartite motif containing 5 (TRIM5), which targets incoming HIV-1 virions by interacting with the viral capsid. In this study, we investigated several methods for overcoming the limited applicability of lentiviral vectors in bovine cells. First, we demonstrated that the SPRY domain of bovine TRIM5 is the major determinant of anti-viral activity. Second, we found that mutations that allow the capsid to evade rhesus macaque TRIM5α minimally rescued HIV-1 infectivity in bovine-derived MDBK cells. Third, we found that cyclosporine A, which relieves the inhibition of HIV-1 infection in monkey cells, significantly rescued the impaired HIV-1 infectivity in MDBK cells. Lastly, we successfully generated a bovine cell line lacking intact TRIM5 using the CRISPR/Cas9 technique. This TRIM5 knockout cell line displayed significantly higher susceptibility to an HIV-1-based lentiviral vector. In conclusion, our findings provide a promising gene engineering strategy for bovine cells, thereby contributing to innovations in agriculture and improvements in animal health.Improving maternal nutrition during pregnancy/lactation is a promising strategy to maximise the intestinal health of piglets undergoing abrupt weaning under commercial production conditions. This experiment investigated the effects of maternal supplementation of a casein hydrolysate and yeast β-glucan (CH-YBG) from day 83 of gestation until weaning (day 28) on sow faecal microbial populations and measures of piglet gastrointestinal health parameters at weaning. Sows (n = 10 sows/group) were assigned to (1) control diet, and (2) control diet + CH-YBG. Maternal supplementation increased the abundance of the phylum Firmicutes, including members Lactobacillus in the sows faeces, with a concomitant increase in the caecal abundance of Lactobacillus in the weaned piglets compared to the controls. Piglets weaned from the supplemented sows had increased villus height in the duodenum (P  less then  0.05) and increased villus height to crypt depth ratio in the jejunum, as well as a decreased expression of the proinflammatory cytokine genes (IL6/TNF/TGFB), the tight junction gene CLDN3 and the mucin gene MUC2 in the duodenum/jejunum compared to the controls (P  less then  0.05). In conclusion, maternal CH-YBG supplementation during pregnancy/lactation improved microbial, structural, and inflammatory measures of gastrointestinal health of piglets at weaning. This is a promising strategy to alleviate the challenges that occur with early abrupt weaning in commercial pig production.Ferroelectricity, existing in either solid crystals or liquid crystals, gained widespread attention from science and industry for over a century. However, ferroelectricity has never been observed in both solid and liquid crystal phases of a material simultaneously. Inorganic ferroelectrics that dominate the market do not have liquid crystal phases because of their completely rigid structure caused by intrinsic chemical bonds. We report a ferroelectric homochiral cholesterol derivative, β-sitosteryl 4-iodocinnamate, where both solid and liquid crystal phases can exhibit the behavior of polarization switching as determined by polarization-voltage hysteresis loops and piezoresponse force microscopy measurements. The unique long molecular chain, sterol structure, and homochirality of β-sitosteryl 4-iodocinnamate molecules enable the formation of polar crystal structures with point group 2 in solid crystal phases, and promote the layered and helical structure in the liquid crystal phase with vertical polarization. Our findings demonstrate a compound that can show the biferroelectricity in both solid and liquid crystal phases, which would inspire further exploration of the interplay between solid and liquid crystal ferroelectric phases.To evaluate retinal and choroidal thickness with optical coherence tomography (OCT) to detect retinal and choroidal pathologies in coronavirus disease 2019 (COVID-19) patients with high D-dimer levels. Thirty patients who were hospitalized in the intensive care unit due to severe acute respiratory syndrome coronavirus 2 and whose D-dimer levels were high during this period, who applied to the internal medicine outpatient clinic between 15 and 30 days after discharge, and 30 healthy volunteers with similar age and gender as the control group was included in the study. After full ophthalmological examination, central foveal and choroidal thicknesses were evaluated using optical coherence tomography. Statistical analysis of the study data demonstrated that there was no significant difference between the groups in terms of age or gender (p > 0.05). There was also no statistically significant difference between the groups in terms of central foveal thickness, central choroidal thickness, or nasal 500, nasal 1500, temporal 500, or temporal 500 micron distances (p > 0.05 for all parameters). Choroidal and retinal vascular thicknesses were not affected in the short term in COVID-19 patients hospitalized in the intensive care unit.The fish immune system is a topic or subject that offers a unique understanding of defensive system evolution in vertebrate heredity. While gut microbiota plays several roles in fish well-being, promoting health and growth, resistance to bacterial invasion, regulation of energy absorption, and lipid metabolism. However, studies on fish gut microbiota face practical challenges due to the large number of fish varieties, fluctuating environmental conditions, and differences in feeding habits. This study was carried out to evaluate the impacts of supplemented three autochthonous strains, Bacillus sp. RCS1, Pantoea agglomerans RCS2, and Bacillus cereus RCS3 mixture diet on cobia fish (Rachycentron canadum). Also, chromatography, mass spectrometry and high throughput sequencing were combined to explore composition and metabolite profile of gut microbiota in juvenile cobia fed with supplemented diet. In the trial group, juvenile cobia received diets supplemented with 1 × 1012 CFU mL-1 autochthonous strains for ten wanced the growth, survival, and innate and adaptive immunities of juvenile cobia.Infection is the most common cause of mortality early in life, yet the broad potential of immunization is not fully realized in this vulnerable population. Most vaccines are administered during infancy and childhood, but in some cases the full benefit of vaccination is not realized in-part. New adjuvants are cardinal to further optimize current immunization approaches for early life. However, only a few classes of adjuvants are presently incorporated in vaccines approved for human use. Recent advances in the discovery and delivery of Toll-like receptor (TLR) agonist adjuvants have provided a new toolbox for vaccinologists. Prominent among these candidate adjuvants are synthetic small molecule TLR7/8 agonists. The development of an effective infant Bordetella pertussis vaccine is urgently required because of the resurgence of pertussis in many countries, contemporaneous to the switch from whole cell to acellular vaccines. In this context, TLR7/8 adjuvant based vaccine formulation strategies may be a promising tool to enhance and accelerate early life immunity by acellular B. pertussis vaccines. In the present study, we optimized (a) the formulation delivery system, (b) structure, and (c) immunologic activity of novel small molecule imidazoquinoline TLR7/8 adjuvants towards human infant leukocytes, including dendritic cells. Upon immunization of neonatal mice, this TLR7/8 adjuvant overcame neonatal hyporesponsiveness to acellular pertussis vaccination by driving a T helper (Th)1/Th17 biased T cell- and IgG2c-skewed humoral response to a licensed acellular vaccine (DTaP). This potent immunization strategy may represent a new paradigm for effective immunization against pertussis and other pathogens in early life.