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The intestinal microbiome plays a crucial role in animal health and growth by interacting with the host, inhibiting pathogenic microbial colonization, and regulating immunity. This study investigated dynamic changes in the fecal microbial composition of piglets from birth through weaning and the relationship between the piglet fecal microbiome and sows. Feces, skin, neonatal oral cavity, and vaginal samples were collected from eight sows and sixty-three piglets, and 16S genome sequencing was performed. The results revealed that Firmicutes, Bacteroidetes, and Proteobacteria dominated the piglet microbiome in the early stages, and Firmicutes and Bacteroidetes were crucial for maintaining a balance in the intestinal microbiome during nursing. The abundance of Christensenellaceae_R-7_group, Succinivibrio, and Prevotella increased in weaned piglets fed solid feed. Analysis of the microbiome from sows to piglets indicated a shift in the microbiome colonizing piglet intestines, which became a significant constituent of the piglet intestinal microbiome. This study supports the theory that the neonatal intestinal microbiome is vertically transmitted from the mother. Further research is required to integrate factors related to sows, piglets, and their environments to gain a better understanding of the early establishment of the intestinal microbiome in piglets.

Background: Optic nerve sheath diameter (ONSD) and its ratio to eyeball transverse diameter (ETD; ONSD/ETD) are potential markers for elevated intracranial pressure in comatose survivors of out-of-hospital cardiac arrest (OHCA). However, their prognostic accuracy remains uncertain. We compared their predictive value via compted tomography (CT)and magnetic resonance imaging (MRI) before and after targeted temperature management (TTM) in OHCA survivors. Methods: This retrospective study included adult comatose OHCA survivors who underwent TTM and serial brain imaging. ONSD and ONSD/ETD ratios were measured on brain CT and MRI at two predefined time-points: within 6 h (pre-TTM) and at 72–96 h (post-TTM) after return of spontaneous circulation. Intra-rater reliability was assessed using intraclass correlation coefficients (ICC). Poor neurological outcome was defined as a Cerebral Performance Category score of 3–5 at 6 months. Prognostic performance was evaluated using area under the receiver operating characteristic curve (AUC). Results: Among 136 patients, 78 (57%) had poor neurological outcomes. Only ONSD (5.12 vs. 5.37 mm) and ONSD/ETD ratio (0.22 vs. 0.23) measured on post-TTM MRI were significantly higher in the poor outcome group. These results depicted modest predictive performance (AUC, 0.67 and 0.65, respectively), whereas all CT-based and early MRI measurements had AUC < 0.60. Intra-rater reliability for ONSD and ETD was higher on CT (ICC: up to 0.93) than on MRI (ICC: 0.73–0.80). Conclusions: Delayed MRI-based ONSD and ONSD/ETD showed statistically significant but modest prognostic value, with limited clinical applicability as a stand-alone tool. These findings underscore the relevance of measurement timing, supporting ONSD as an adjunctive, rather than definitive, tool in multimodal prognostication.

RNA-binding proteins (RBPs) provide a critical post-transcriptional regulatory layer in determining RNA fate. Currently, UV crosslinking followed by oligo-dT pull-down is the gold standard in identifying the RBP repertoire of poly-adenylated RNAs, but such method is ineffective in capturing RBPs that recognize double-stranded RNAs (dsRNAs). Here, we utilize anti-dsRNA K1 antibody immunoprecipitation followed by quantitative mass spectrometry to comprehensively identify RBPs bound to cellular dsRNAs without external stimulus. Notably, our dsRNA interactome contains proteins involved in sensing N 6 -methyladenosine RNAs and stress granule components. We further perform targeted CRISPR-Cas9 knockout functional screening and discover proteins that can regulate the interferon (IFN) response during exogenous RNA sensing. Interestingly, most dsRBPs promote IFN-β secretion in response to dsRNA stimulation and act as antiviral factors during HCoV-OC43 infection. Our dsRNA interactome capture provides an unbiased and comprehensive characterization of putative dsRBPs and will facilitate our understanding of dsRNA sensing in physiological and pathological contexts. Exploration of dsRNA interactome using the K1 antibody and functional studies using CRISPR-Cas9 knockout screening of these dsRBP candidates elucidate the role of dsRNA interactome in immune responses and their importance in viral infection.

Due to a pivotal role in the post-transcriptional regulation of genes implicated in numerous diseases, miRNAs serve as promising disease biomarkers and therapeutic targets. We introduce a new oligonucleotide probe termed miRNA-trigger, which selectively downregulates newly assigned target mRNAs by hijacking specific miRNAs. By engineering the miRNA-trigger to suppress the anti-apoptotic BCL-xL gene, we induce apoptosis selectively in breast cancer cells overexpressing specific miRNAs and further validate its therapeutic efficacy in vivo, by significantly reducing the tumor volume of the xenograft mouse upon its tail-vein injection. This approach establishes a new platform for self-modulating oligonucleotide therapy by redirecting disease-associated miRNAs. Graphical Abstract

Strong evidence exists for polyploidy having occurred during the evolution of the tribe Brassiceae. We show evidence for the dynamic and ongoing diploidization process by comparative analysis of the sequences of four paralogous Brassica rapa BAC clones and the homologous 124-kb segment of Arabidopsis thaliana chromosome 5. We estimated the times since divergence of the paralogous and homologous lineages. The three paralogous subgenomes of B. rapa triplicated 13 to 17 million years ago (MYA), very soon after the Arabidopsis and Brassica divergence occurred at 17 to 18 MYA. In addition, a pair of BACs represents a more recent segmental duplication, which occurred ~0.8 MYA, and provides an exception to the general expectation of three paralogous segments within the B. rapa genome. The Brassica genome segments show extensive interspersed gene loss relative to the inferred structure of the ancestral genome, whereas the Arabidopsis genome segment appears little changed. Representatives of all 32 genes in the Arabidopsis genome segment are represented in Brassica, but the hexaploid complement of 96 has been reduced to 54 in the three subgenomes, with compression of the genomic region lengths they occupy to between 52 and 110 kb. The gene content of the recently duplicated B. rapa genome segments is identical, but intergenic sequences differ.

The classification and recommendation system for identifying social networking site (SNS) users’ interests plays a critical role in various industries, particularly advertising. Personalized advertisements help brands stand out from the clutter of online advertisements while enhancing relevance to consumers to generate favorable responses. Although most user interest classification studies have focused on textual data, the combined analysis of images and texts on user-generated posts can more precisely predict a consumer’s interests. Therefore, this research classifies SNS users’ interests by utilizing both texts and images. Consumers’ interests were defined using the Curlie directory, and various convolutional neural network (CNN)-based models and recurrent neural network (RNN)-based models were tested for our user interest classification system. In our hybrid neural network (NN) model, CNN-based classification models were used to classify images from users’ SNS postings while RNN-based classification models were used to classify textual data. The results of our extensive experiments show that the classification of users’ interests performed best when using texts and images together, at 96.55%, versus texts only, 41.38%, or images only, 93.1%. Our proposed system provides insights into personalized SNS advertising research and informs marketers on making (1) interest-based recommendations, (2) ranked-order recommendations, and (3) real-time recommendations.

The purpose of this study was to carry out systematic review of the literature and meta-analysis to evaluate the diagnostic utility of cerebrospinal fluid (CSF) levels of the 42 amino acid form of amyloid-beta (Aβ1-42) as a biomarker for differentiating Alzheimer's disease (AD) from non-AD dementia. Design. Systematic literature review was used to evaluate the effectiveness of the Aβ for the diagnosis of AD. The Scottish Intercollegiate Guidelines Network (SIGN) tool was used to evaluate independently the quality of the studies. Data sources. The literature review covered from January 1, 2004, to October 22, 2013, and searched eight domestic databases including Korea Med and international databases including Ovid-MEDLINE, EMBASE, and Cochrane Library. Data Extraction and Synthesis. Primary criteria for inclusion were valid studies on (i) patients with mild cognitive impairment with confirmed or suspected AD and non-AD dementia, and (ii) assessment of Aβ1-42 levels using appropriate comparative tests. A total of 17 diagnostic evaluation studies were identified in which levels of CSF Aβ1-42 were assessed. Meta-analysis was performed on 11 robust studies that compared confirmed AD (n = 2211) with healthy individuals (n = 1030), 10 studies that compared AD with non-AD dementias (n = 627), and 5 studies that compared amnestic mild cognitive impairment (n = 1133) with non-amnestic type subjects (n = 1276). Overall, the CSF Aβ1-42 levels were reduced in AD compared to controls or non-AD dementia. The effectiveness of test was evaluated for diagnostic accuracy (pooled sensitivity, 0.80 (95% CI 0.78-0.82); pooled specificity, 0.76 (95% CI 0.74-0.78). Reduced CSF Aβ1-42 levels are of potential utility in the differential diagnosis of AD versus non-AD dementias and controls. Diagnostic accuracy was high in AD versus healthy controls. However, differential diagnosis for MCI or non-AD might be evaluated by other biomarkers.

Heterogeneity in the etiopathology of autism spectrum disorders (ASD) limits the development of generic remedies, requires individualistic and patient-specific research. Recent progress in human-induced pluripotent stem cell (iPSC) technology provides a novel platform for modeling ASDs for studying complex neuronal phenotypes. In this study, we generated telencephalic induced neuronal (iN) cells from iPSCs derived from an ASD patient with a heterozygous point mutation in the DSCAM gene. The mRNA of DSCAM and the density of DSCAM in dendrites were significantly decreased in ASD compared to control iN cells. RNA sequencing analysis revealed that several synaptic function-related genes including NMDA receptor subunits were downregulated in ASD iN cells. Moreover, NMDA receptor (R)-mediated currents were significantly reduced in ASD compared to control iN cells. Normal NMDA-R-mediated current levels were rescued by expressing wild-type DSCAM in ASD iN cells, and reduced currents were observed by truncated DSCAM expression in control iN cells. shRNA-mediated DSCAM knockdown in control iN cells resulted in the downregulation of an NMDA-R subunit, which was rescued by the overexpression of shRNA-resistant DSCAM. Furthermore, DSCAM was co-localized with NMDA-R components in the dendritic spines of iN cells whereas their co-localizations were significantly reduced in ASD iN cells. Levels of phospho-ERK1/2 were significantly lower in ASD iN cells, suggesting a potential mechanism. A neural stem cell-specific Dscam heterozygous knockout mouse model, showing deficits in social interaction and social memory with reduced NMDA-R currents. These data suggest that DSCAM mutation causes pathological symptoms of ASD by dysregulating NMDA-R function.

Cytomegalovirus (CMV) has recently emerged as a significant cause of anterior uveitis (AU) with intraocular pressure (IOP) elevation and corneal endothelial damage. The purpose of this study is to investigate the long-term prognostic factors for glaucoma surgery in patients with CMV-AU. In this retrospective cohort study, immunocompetent patients with CMV-AU were included from one academic institution and a uveitis-specialized private clinic between May 2015 and Mar 2024. Upon confirmation of polymerase-chain-reaction results, patients received anti-viral therapy (oral valganciclovir or 2% topical ganciclovir). When intraocular pressure was not controlled, glaucoma surgery (glaucoma filtering surgery or glaucoma drainage device) were performed. Indicators of glaucoma surgery were analyzed using Kaplan-Meir survival analyses and Cox-proportional hazard model. A total of 149 consecutive patients with CMV-AU included with a mean age of 44.5 ± 16.5 years; 65.1% being male. The baseline corneal endothelial cell (EC) density in affected eyes was 2088 ± 695 cells/mm 2 . During follow-up, glaucoma surgery was performed in 24 patients (16.1%), of whom 75% underwent glaucoma filtering surgery and 25% underwent drainage device implantation. The median survival time from the first onset of the disease to glaucoma surgery was 73.0 ± 11.6 months. In the univariate Cox-regression analyses for receiving glaucoma surgery, baseline EC < 1000 cells/mm 2 (Exp(B) = 4.142, p  = 0.013), baseline BCVA < 0.3 (Exp(B) = 2.733, p  = 0.029), and number of anti-glaucoma medications at quiescent phase ≥ 2 (Exp(B) = 2.645, p  = 0.024) were significantly associated with the future requirement for glaucoma surgery. In the multivariate analyses, baseline EC < 1000 cells/mm 2 was the only significant factor for predicting glaucoma surgery (Exp(B) = 3.960, p  = 0.022). In conclusion, baseline corneal endothelial cell density can serve as a useful indicator for future requirement of glaucoma surgery in CMV-AU.

Hypotension in the early stages of life appears in 20% of very low birth weight (VLBW) infants. The gestational age and birth weight are the risk factors highly related to the postnatal hypotension. Other risk factors slightly differ between different studies. So, we evaluated the risk factors and prognosis that are associated with infants treated with hypotension in the early stages of life, after excluding the influences of gestational age and small for gestational age (SGA). VLBW infants registered in the Korean Neonatal Network between 2013 and 2015 treated for hypotension within a week after their birth were selected as study subjects. The rest were used as a control group. Risk factors and the prevalence of severe complications, including mortality, were investigated and compared after matching for gestational age and SGA. The treatment rate for hypotension within the first postnatal week was inversely related to decreasing gestational ages and birth weights. In particular, 63.4% of preterm infants born at ≤ 24 weeks’ gestation and 66.9% of those with a birth weight < 500 g were treated for hypotension within a week of birth. Regression analysis after matching showed that 1-minute Apgar score, neonatal cardiac massage or epinephrine administration, symptomatic patent ductus arteriosus, early onset sepsis, and chorioamnionitis were significantly associated with hypotension. In the hypotension group, mortality, grade 3 or higher intraventricular hemorrhage, periventricular leukomalacia, and moderate to severe bronchopulmonary dysplasia rates were significantly higher after the matching for gestational age and SGA. Hypotension during the first postnatal week is very closely related to the prematurity and the condition of the infant shortly after birth. Regular prenatal care including careful monitoring and appropriate neonatal resuscitation are very crucial to decrease the risk of hypotension in the early stages of life.