Miracle-dz/UniFAR-FTUs huggingface dataset:
Different feeding strategies can affect growth performance and rumen functions in Gangba sheep as revealed by integrated transcriptome and microbiome analyses

Due to the harsh environment in the Tibetan Plateau, traditional grazing greatly limits the growth potential of local animals and causes severe ecosystem degradation. This is an urgent issue to be solved, which requires alternative strategies for grazing animals in the Tibetan alpine pastoral livestock systems. This study aimed to investigate the effects of different feeding strategies on growth performance and ruminal microbiota-host interactions in the local breed of sheep (Gangba sheep). Thirty 9-month old Gangba sheep (n = 10 per group) were assigned to natural grazing (G), semi-grazing with supplementation (T), and barn feeding (F) groups (supplementation of concentrate and oat hay) based on body weight. At the end of the experiment (75 d), all sheep were weighed, rumen fluid was obtained from six sheep per group, and ruminal epithelium was obtained from 3 sheep per group. The results showed that: (1) Compared with the G and T groups, the F group significantly increased dry matter intake, average daily gain, and feed conversion ratio of animals. Additionally, Gangba sheep in the F group had higher concentrations of ruminal short-chain volatile fatty acids (VFAs), especially propionate and butyrate (P <0.05) than sheep in the G and T groups. (2) The principal coordinates analysis indicated a significant difference in bacterial composition among different feed strategies. More specifically, the relative abundance of propionate (unidentified F082 and Succiniclasticum) and butyrate-producing (Eubacterium_coprostanoligenes_group) genera were also observed to be increased in the F group, in which unidentified F082 was identified as a differential biomarker among the three groups according to linear discriminant analysis effect size analysis. (3) The dynamics of the rumen epithelial transcriptome revealed that ECM-receptor interactions, focal adhesion, and PI3K-Akt signaling pathways, which are critical in mediating many aspects of cellular functions such as cell proliferation and motility, were upregulated in the F group. In conclusion, under harsh conditions in the Tibetan alpine meadow, barn feeding increased ruminal VFAs concentrations (especially propionate and butyrate), which stimulated gene expression related to cell proliferation in rumen epithelium, appearing to be superior to natural grazing and semi-grazing in gaining body weight of the local Gangba sheep.
Group-based trajectory analysis of acute pain after spine surgery and risk factors for rebound pain

Background This retrospective study was designed to explore the types of postoperative pain trajectories and their associated factors after spine surgery. Materials and methods This study was conducted in a single medical center, and patients undergoing spine surgery with intravenous patient-controlled analgesia (IVPCA) for postoperative pain control between 2016 and 2018 were included in the analysis. Maximal pain scores were recorded daily in the first postoperative week, and group-based trajectory analysis was used to classify the variations in pain intensity over time and investigate predictors of rebound pain after the end of IVPCA. The relationships between the postoperative pain trajectories and the amount of morphine consumption or length of hospital stay (LOS) after surgery were also evaluated. Results A total of 3761 pain scores among 547 patients were included in the analyses and two major patterns of postoperative pain trajectories were identified: Group 1 with mild pain trajectory (87.39%) and Group 2 with rebound pain trajectory (12.61%). The identified risk factors of the rebound pain trajectory were age less than 65 years (odds ratio [OR]: 1.89; 95% CI: 1.12–3.20), female sex (OR: 2.28; 95% CI: 1.24–4.19), and moderate to severe pain noted immediately after surgery (OR: 3.44; 95% CI: 1.65–7.15). Group 2 also tended to have more morphine consumption (p < 0.001) and a longer length of hospital stay (p < 0.001) than Group 1. Conclusion The group-based trajectory analysis of postoperative pain provides insight into the patterns of pain resolution and helps to identify unusual courses. More aggressive pain management should be considered in patients with a higher risk for rebound pain after the end of IVPCA for spine surgery.
Molecular characterization and functional analysis of DIGIRR from golden pompano (Trachinotus ovatus)

Mammalian single immunoglobulin (Ig) interleukin-1 receptor related molecule (SIGIRR), an important member of the Toll/interleukin-1 receptor (TIR) family, plays important balancing roles in the inflammatory responses. In the present study, the double Ig interleukin-1 receptor related molecule (DIGIRR), the homologous of SIGIRR, was characterized in golden pompano (Trachinotus ovatus) (termed as trDIGIRR). The full-length cDNA of trDIGIRR was 2,167 bp with an open reading frame (ORF) of 1,572 bp encoding 523 amino acids. The trDIGIRR contained several conserved domains including a signal peptide, two Ig domains, a transmembrane domain and a TIR domain, and shared high sequence identities with its teleost counterparts. Realtime qPCR analysis revealed that the trDIGIRR was distributed in all tissues examined, with high expressions in intestine, liver and head kidney. The expressions of trDIGIRR were induced by Vibrio alginolyticus, lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid (poly I:C) challenge. Further analysis revealed that trDIGIRR was mainly located in the cytoplasm. In addition, the co-immunoprecipitation (co-IP) assay identified that trDIGIRR could interact with myeloid differentiation factor 88 (MyD88), but not interact with TIR domain containing adaptor protein inducing interferon-β (TRIF). Our results provide basis for studying the immune role of fish DIGIRR.
Weighted gene co-expression identification of CDKN1A as a hub inflammation gene following cardiopulmonary bypass in children with congenital heart disease

Background Congenital heart disease (CHD) is the most common type of birth defect. Most patients with CHD require surgery, and cardiopulmonary bypass (CPB) is the most common surgery performed. Methods The present study utilized weighted gene co-expression network analysis (WGCNA) to identify key inflammation genes after CPB for CHD. The GSE132176 dataset was downloaded from the Gene Expression Omnibus(GEO) database for WGCNA to identify the modules closely related to clinical traits. Disease enrichment, functional annotation and pathway enrichment were performed on genes in the module closely related to clinical traits using Enrichr and Metascape. Immune infiltration analysis was also performed on the training dataset using CIBERSORT. Finally, we identified hub genes using high gene significance (GS), high module members (MMs) and Cytoscape, and we verified the hub genes using an independent dataset and Western blot analysis. Results WGCNA showed that the brown module with 461 genes had the highest correlation to CHD after CPB. Functional annotation and pathway enrichment analysis were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, which showed that genes in the brown module were enriched in inflammation-related pathways. In the disease enrichment analysis, genes in the brown module were enriched for inflammatory diseases. After the 30 most highly associated brown intramodular genes were screened, a protein-protein interaction network was constructed using the STRING online analysis website. The protein-protein interaction results were then calculated using 12 algorithms in the cytoHubba plugin of Cytoscape software. The final result showed that CDKN1A was the fundamental gene of post-CPB for CHD. Using another independent validation dataset (GSE12486), we confirmed that CDKN1A was significantly differentially expressed between preoperative and postoperative CPB (Wilcoxon, P = 0.0079; T-test, P = 0.006). In addition, CDKN1A expression was elevated in eosinophils, neutrophils, memory CD4 T cells and activated mast cells. Western blot analysis showed that the expression of CDKN1A protein was significantly higher postoperative CPB than preoperative CPB. Moreover, CDKN1A was mainly related to inflammation. Conclusion In summary, we found a relationship between CDKN1A and inflammation after CPB for congenital heart disease by WGCNA, experiments and various bioinformatics methods. Thus, CDKN1A maybe serve as a biomarker or therapeutic target for accurate diagnosis and treatment of inflammation after CPB in the future.
Network pharmacology and experimental analysis to reveal the mechanism of Dan-Shen-Yin against endothelial to mesenchymal transition in atherosclerosis

Atherosclerosis is a chronic inflammatory disease characterized by the formation of plaque and endothelial dysfunction. Under pro-inflammatory conditions, endothelial cells adopt a mesenchymal phenotype by a process called endothelial-to-mesenchymal transition (EndMT) which plays an important role in the pathogenesis of atherosclerosis. Dan-Shen-Yin (DSY) is a well-known traditional Chinese medicine used in the treatment of cardiovascular disease. However, the molecular mechanism whereby DSY mitigates atherosclerosis remains unknown. Therefore, we employed a network pharmacology-based strategy in this study to determine the therapeutic targets of DSY, and in vitro experiments to understand the molecular pharmacology mechanism. The targets of the active ingredients of DSY related to EndMT and atherosclerosis were obtained and used to construct a protein-protein interaction (PPI) network followed by network topology and functional enrichment analysis. Network pharmacology analysis revealed that the PI3K/AKT pathway was the principal signaling pathway of DSY against EndMT in atherosclerosis. Molecular docking simulations indicated strong binding capabilities of DSY’s bioactive ingredients toward PI3K/AKT pathway molecules. Experimentally, DSY could efficiently modify expression of signature EndMT genes and decrease expression of PI3K/AKT pathway signals including integrin αV, integrin β1, PI3K, and AKT1 in TGF-β2-treated HUVECs. LASP1, which is upstream of the PI3K/AKT pathway, had strong binding affinity to the majority of DSY’s bioactive ingredients, was induced by EndMT-promoting stimuli involving IL-1β, TGF-β2, and hypoxia, and was downregulated by DSY. Knock-down of LASP1 attenuated the expression of integrin αV, integrin β1, PI3K, AKT1 and EndMT-related genes induced by TGF-β2, and minimized the effect of DSY. Thus, our study showed that DSY potentially exerted anti-EndMT activity through the LASP1/PI3K/AKT pathway, providing a possible new therapeutic intervention for atherosclerosis.
Effectiveness of bimodal auditory and electrical stimulation in patients with tinnitus: A feasibility study

Background Tinnitus is a common symptom, affecting about 10–15% of the adult population. When input from the somatosensory system can influence and/or elicit tinnitus, this type of subjective tinnitus is called somatosensory tinnitus. Recently, a new type of bimodal neurostimulation treatment has shown promising results for a specific subgroup within the somatosensory tinnitus population. It is, however, not clear if this bimodal stimulation is also effective in patients with other types of subjective tinnitus. Aim The aim of this study was to evaluate the feasibility and efficacy of non-invasive bimodal auditory-somatosensory stimulation in reducing tinnitus severity among a general population of people with subjective tinnitus. Methods Chronic subjective tinnitus patients were recruited from the ENT department of the Antwerp University Hospital. Somatosensory stimulation was delivered by Transcutaneous Electrical Nerve Stimulation (TENS), and it was combined with auditory stimulation via headphones. The therapy comprised six sessions of thirty minutes twice a week for a period of 3 consecutive weeks. Follow up measurements were scheduled 9–12 weeks after the last treatment session. The change of the Tinnitus Functional Index (TFI) score, a questionnaire evaluating tinnitus burden and effects on the quality of life, was the primary outcome measure. Results Twenty-nine patients were enrolled in the study. A linear mixed-effects model was used to analyze the efficacy of bimodal treatment. The results of this analysis showed a statistically significant decrease (by 6, 9 points) in average TFI score at the follow up visit when compared to baseline. The ability to modulate tinnitus did not have an influence on the treatment results. Conclusion Our study showed that bimodal stimulation is a feasible and safe method of tinnitus treatment. The method might be an effective treatment for some participants with tinnitus, especially those who have accompanying neck/temporomandibular problems, although, the evidence from this trial is quite weak. Additional research is needed toward establishing the optimal treatment protocol, as well as selecting the most appropriate inclusion criteria.
Transcriptome sequencing reveals differences between leydig cells and sertoli cells of yak

In this study, we detected the expression of mRNAs, lncRNAs, and miRNAs in primary cultured leydig cells (LCs) and sertoli cells (SCs) of yak by RNA sequencing technology. A total of 84 differently expression mRNAs (DEmRNAs) (LCs vs. SCs: 15 up and 69 down), 172 differently expression lncRNAs (DElncRNAs) (LCs vs. SCs: 36 up and 136 down), and 90 differently expression miRNAs (DEmiRNAs) (LCs vs. SCs: 72 up and 18 down) were obtained between the two types of cells. GO enrichment and KEGG analysis indicated that the differential expression genes (DEGs) were more enriched in the regulation of actin cytoskeleton, Rap1/MAPK signaling pathway, steroid biosynthesis, focal adhesion, and pathways associated with metabolism. Targeted regulation relationship pairs of 3β-HSD and MSTRG.54630. 1, CNTLN and MSTRG.19058. 1, BRCA2 and MSTRG.28299. 4, CA2 and novel-miR-148, and ceRNA network of LAMC3-MSTRG.68870. 1- bta-miR-7862/novel-miR-151/novel-miR-148 were constructed by Cytoscape software. In conclusion, the differences between LCs and SCs were mainly reflected in steroid hormone synthesis, cell proliferation and metabolism, and blood-testicular barrier (BTB) dynamic regulation, and 3β-HSD, CNTLN, BRCA2, CA2, and LAMC3 may be the key factors causing these differences, which may be regulated by ncRNAs. This study provides a basic direction for exploring the differential regulation of LCs and SCs by ncRNAs.
Digital Optical Switches with a Silicon-on-Insulator Waveguide Corner

In this chapter, the quantum process of the Goos-Hänchen (GH) spatial shift is first derived out, then the coherence between spatial and angular shifts in the GH effect in the quantum state is discovered and a function of digital optical switch is developed. It is found that a waveguide corner structure always makes the reflected guide-mode have both the GH spatial and angular shifts when the incident beam is in the vicinity area of critical and Brewster angles. Meanwhile, these two GH shifts have the interesting coherent distributions with the incident angle, and only in the common linear response area the two GH shifts are mutual enhancing, then a mini refractive index modulation (RIM) of guided mode at the reflecting interface can create a great stable jump of reflected beam displacement at an eigenstate. As a result, on 220 nm silicon-on-insulator (SOI) waveguide platform, with a tapered multimode interference (MMI) waveguide a 5.0 × 10 18 cm − 3 concentration variation of free carriers can cause a digital total 8–25 μm displacement of the reflected beam on the MMI output end, leading to a 1 × N scale digital optical switching function. As a series of verifications, the numerical calculations, finite difference time domain (FDTD) simulations and experiments, are sustainable to the quantum GH shifts. of total GH displacement, and digital optical switch
A directed genome evolution method to enhance hydrogen production in Rhodobacter capsulatus

Nitrogenase-dependent H2 production by photosynthetic bacteria, such as Rhodobacter capsulatus, has been extensively investigated. An important limitation to increase H2 production using genetic manipulation is the scarcity of high-throughput screening methods to detect possible overproducing mutants. Previously, we engineered R. capsulatus strains that emitted fluorescence in response to H2 and used them to identify mutations in the nitrogenase Fe protein leading to H2 overproduction. Here, we used ultraviolet light to induce random mutations in the genome of the engineered H2-sensing strain, and fluorescent-activated cell sorting to detect and isolate the H2-overproducing cells from libraries containing 5 × 105 mutants. Three rounds of mutagenesis and strain selection gradually increased H2 production up to 3-fold. The whole genomes of five H2 overproducing strains were sequenced and compared to that of the parental sensor strain to determine the basis for H2 overproduction. No mutations were present in well-characterized functions related to nitrogen fixation, except for the transcriptional activator nifA2. However, several mutations mapped to energy-generating systems and to carbon metabolism-related functions, which could feed reducing power or ATP to nitrogenase. Time-course experiments of nitrogenase depression in batch cultures exposed mismatches between nitrogenase protein levels and their H2 and ethylene production activities that suggested energy limitation. Consistently, cultivating in a chemostat produced up to 19-fold more H2 than the corresponding batch cultures, revealing the potential of selected H2 overproducing strains.
Putative COVID-19 therapies imatinib, lopinavir, ritonavir, and ivermectin cause hair cell damage: A targeted screen in the zebrafish lateral line

The biomedical community is rapidly developing COVID-19 drugs to bring much-need therapies to market, with over 900 drugs and drug combinations currently in clinical trials. While this pace of drug development is necessary, the risk of producing therapies with significant side-effects is also increased. One likely side-effect of some COVID-19 drugs is hearing loss, yet hearing is not assessed during preclinical development or clinical trials. We used the zebrafish lateral line, an established model for drug-induced sensory hair cell damage, to assess the ototoxic potential of seven drugs in clinical trials for treatment of COVID-19. We found that ivermectin, lopinavir, imatinib, and ritonavir were significantly toxic to lateral line hair cells. By contrast, the approved COVID-19 therapies dexamethasone and remdesivir did not cause damage. We also did not observe damage from the antibiotic azithromycin. Neither lopinavir nor ritonavir altered the number of pre-synaptic ribbons per surviving hair cell, while there was an increase in ribbons following imatinib or ivermectin exposure. Damage from lopinavir, imatinib, and ivermectin was specific to hair cells, with no overall cytotoxicity noted following TUNEL labeling. Ritonavir may be generally cytotoxic, as determined by an increase in the number of TUNEL-positive non-hair cells following ritonavir exposure. Pharmacological inhibition of the mechanotransduction (MET) channel attenuated damage caused by lopinavir and ritonavir but did not alter imatinib or ivermectin toxicity. These results suggest that lopinavir and ritonavir may enter hair cells through the MET channel, similar to known ototoxins such as aminoglycoside antibiotics. Finally, we asked if ivermectin was ototoxic to rats in vivo. While ivermectin is not recommended by the FDA for treating COVID-19, many people have chosen to take ivermectin without a doctor’s guidance, often with serious side-effects. Rats received daily subcutaneous injections for 10 days with a clinically relevant ivermectin dose (0.2 mg/kg). In contrast to our zebrafish assays, ivermectin did not cause ototoxicity in rats. Our research suggests that some drugs in clinical trials for COVID-19 may be ototoxic. This work can help identify drugs with the fewest side-effects and determine which therapies warrant audiometric monitoring.
CDK4/6 inhibitors versus PI3K/AKT/mTOR inhibitors in women with hormone receptor-positive, HER2-negative metastatic breast cancer: An updated systematic review and network meta-analysis of 28 randomized controlled trials

Background Updated evidence was required to compare the efficacy and safety of cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) inhibitors for patients with hormone receptor-positive and HER2-negative metastatic breast cancer. Methods A systematic review and network meta-analysis was conducted utilizing data from randomized controlled trials (RCTs) that contained interventions of CDK4/6 inhibitors or PI3K/AKT/mTOR inhibitors. Progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs) were primary outcomes of interest. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% credible intervals (CrIs) were used to assess the survival outcomes and safety profiles, respectively. Results A total of 28 RCTs with 12,129 participants were included. Pooled analysis showed that CDK4/6 inhibitors significantly prolonged PFS than PI3K/AKT/mTOR inhibitors (HR, 0.81; 95% CrI, 0.69–0.94), whereas no significant differences were detected regarding OS. After balancing the treatment lines and metastatic sites, the superiority of CDK4/6 inhibitors only appeared in the visceral and non-visceral subgroups. Among CDK4/6 inhibitors, abemaciclib was significantly better than others in ≥3 grade neutropenia (OR, 0.04; 95% CrI, 0.01–0.15). The incidence of stomatitis and digestive disorders was different among diverse kinds of PI3K/AKT/mTOR inhibitors. Discrepancies appeared regarding TRAEs of hepatotoxicity, diarrhea, and hyperglycemia among different interventions. Conclusions CDK4/6 inhibitors showed better efficacy in PFS, but the benefits disappeared when taking treatment line into consideration. Specific and discrepant safety profiles were found in two categories of agents. Systematic Review Registration https://www.crd. york.ac. uk/PROSPERO, identifier CRD42022321172.