Miracle-dz/UniFAR-FTUs huggingface dataset:
Investigating the pharmacological mechanisms of SheXiang XinTongNing against coronary heart disease based on network pharmacology

Background SheXiang XinTongNing, a commercially available Chinese patent medicine, has been widely used in the treatment of coronary heart disease. However, the mechanisms of SheXiang XinTongNing are still unclear. The aim of this study was to investigate the pharmacological mechanisms of SheXiang XinTongNing against coronary heart disease via network analysis. Method The traditional Chinese medicine system pharmacology analysis platform was used to screen the potential active constituents of the six traditional Chinese medicines in SheXiang XinTongNing, and the potential targets were obtained from PharmMapper. The genome annotation database platform was used to screen the candidate targets related to coronary heart disease. Then the drug-components-targets network and protein interaction network were built by Cytoscape 3.6. 0 software. Further, GO bio-functional enrichment analysis and KEGG pathway enrichment analysis were performed through annotation, visualization and integrated discovery database. Results Results showed that the drugs-components-targets network contains 104 targets and 62 key components. The protein interaction network consisted of 107 nodes; key targets included Bcl2l1, IGF1, SRC, CASP3, et al. Functionally, the candidate targets were significantly associated with multiple pathways such as PI3K-Akt signaling pathway, MAPK signaling pathway, Ras signaling pathway, FoxO signaling pathway, Endocrine resistance. Given the above, the pharmacological activities of SheXiang XinTongNing may be predominantly related to several factors such as cell apoptosis, inflammation and angiogenesis. Conclusion XTN can effectively attenuate the symptoms of coronary heart disease through diverse pathways. The research proves that network pharmacology can successfully reveal the mechanisms of traditional Chinese medicine in a holistic view. Our systematic analysis lays a foundation for further studying.
Predictive ability of motion sickness susceptibility questionnaire for seasickness individual difference in Chinese military personnel

Background Motion sickness susceptibility questionnaire (MSSQ) has been widely used for assessing individual differences in motion sickness. The present study tried to investigate its efficacy for predicting seasickness susceptible (SUS) and insusceptible (INSUS) subjects among Chinese military personnel. Methods Two cohorts of young male army volunteers were exposed to real ship motion (n=125) and laboratory vertical oscillation motion (n=77). Predictive ability of the MSSQ and its vomiting (MSV) and nausea (MSN) subscales (including child and adult subitems) was examined via analyzing area under the curve (AUC) of receiver operating characteristic (ROC) with seasickness susceptibility defined by Graybiel score or nausea latency. Results Higher Graybiel scores and lower percentage of INSUS subjects was observed in the ship motion trial than the vertical oscillation trial. MSSQ and its subscales positively correlated with the Graybiel score in both trials. The MSN child showed no predictive ability for the INSUS subjects, leading to lower AUC of the MSN than the MSSQ and the MSV for INSUS prediction in ship motion (0.587 vs. 0.647 and 0.644, P < 0.01) and vertical oscillation trial (0.696 vs. 0.761 and 0.788, P < 0.01 and 0.05) when seasickness susceptibility was defined by Graybiel score. Lower AUC in the MSN than the MSSQ (0.691 vs. 0.758, P < 0.05 and 0.01) was observed due to invalidity of MSN child when susceptibility was defined by nausea latency in the vertical oscillation trial. The prediction ability of SUS did not differ among the MSSQ and its subscales in both trials. Relative to the ship motion trial, the vertical oscillation trial showed higher predictive efficacy of the MSSQ for the Graybiel score-defined SUS subjects (0.840 vs. 0.686, P < 0.05) as a result of higher AUC in both the MSV (0.840 vs. 0.690, P < 0.05) and the MSN (0.806 vs. 0.651, P < 0.01). Conclusions The MSSQ was effective for predicting seasickness susceptibility in young male Chinese military members, but the efficacy varies with motion intensity and complexity and the vomiting scale should be recommended for application.
Sustainable Green Concrete by using Biomass Aggregate

The use of concrete for construction had become very common in developing countries. But concrete is not friendly environment because of it consumes huge quantities of natural materials and production of the cement, which is a major contributor to greenhouse gas emissions and global warming. The aim of this study is to investigate the Sustainable Green Concrete (SGC) which containing biomass aggregate; fly ash and Superplasticizer. Biomass aggregate and fly ash are waste industry products which are environmentally friendly. The study was carried out to identify the chemical properties of biomass aggregate, and to determine the chemical properties and optimum mix design of the Sustainable Green Concrete (SGC). A total of 90 cube samples were casted and compressive strength were tested at the age of 7, 14 and 28 days. The overall results showed that the workability and compressive strength were decreased with the increase of the replacement of natural aggregate with biomass aggregate. Besides that, the workability and compressive strength was increased with the incorporation with the replacement cement by fly ash. The SGC gained highest compressive strength for the concrete mixes of 39.3 N/mm2 with the optimum percentage used of SGC in producing concrete not exceeding 30% biomass aggregate and 6% of fly ash as a partial replacement with natural aggregate and cement respectively. The results obtained and observation made in this study suggested that biomass aggregate and fly ash are successfully used as partial replacement in producing SGC and can perform better strength development.
Horizontal and vertical transmission of transgenerational memories via the Cer1 transposon

Animals face both external and internal dangers: pathogens threaten from the environment, and unstable genomic elements threaten from within. Previously, we discovered that C. elegans protects itself from pathogens by “reading” bacterial small RNAs and using this information to both induce avoidance and transmit memories for several generations. Here we found that these memories can be transferred to naïve animals via Cer1 retrotransposon-encoded capsids. Cer1 functions at the step of transmission of information from the germline to neurons, and is required for C. elegans’ learned avoidance ability and for mothers to pass this information on to progeny. The presence of the Cer1 retrotransposon in wild C. elegans strains correlates with the ability to learn and inherit small RNA-induced pathogen avoidance. Together, these results suggest that C. elegans has co-opted a potentially dangerous retrotransposon to instead protect itself and its progeny from a common pathogen through its inter-tissue signaling ability, hijacking this genomic element for its own adaptive immunity benefit.
A genome-scale yeast library with inducible expression of individual genes

The ability to switch a gene from off to on and monitor dynamic changes provides a powerful approach for probing gene function and elucidating causal regulatory relationships, including instances of feedback control. Here, we developed and characterized YETI (Yeast Estradiol strains with Titratable Induction), a collection in which 5,687 yeast genes are engineered for transcriptional inducibility with single-gene precision at their native loci and without plasmids. Each strain contains Synthetic Genetic Array (SGA) screening markers and a unique molecular barcode, enabling high-throughput yeast genetics. We characterized YETI using quantitative growth phenotyping and pooled BAR-seq screens, and we used a YETI allele to characterize the regulon of ROF1, showing that it is a transcriptional repressor. We observed that strains with inducible essential genes that have low native expression can often grow without inducer. Analysis of data from other eukaryotic and prokaryotic systems shows that low native expression is a critical variable that can bias promoter-perturbing screens, including CRISPRi. We engineered a second expression system, Z3EB42, that gives lower expression than Z3EV, a feature enabling both conditional activation and repression of lowly expressed essential genes that grow without inducer in the YETI library.
Structural insights into Cullin4-RING ubiquitin ligase remodelling by Vpr from simian immunodeficiency viruses

Viruses have evolved means to manipulate the host’s ubiquitin-proteasome system, in order to down-regulate antiviral host factors. The Vpx/Vpr family of lentiviral accessory proteins usurp the substrate receptor DCAF1 of host Cullin4-RING ligases (CRL4), a family of modular ubiquitin ligases involved in DNA replication, DNA repair and cell cycle regulation. CRL4DCAF1 specificity modulation by Vpx and Vpr from certain simian immunodeficiency viruses (SIV) leads to recruitment, poly-ubiquitylation and subsequent proteasomal degradation of the host restriction factor SAMHD1, resulting in enhanced virus replication in differentiated cells. To unravel the mechanism of SIV Vpr-induced SAMHD1 ubiquitylation, we conducted integrative biochemical and structural analyses of the Vpr protein from SIVs infecting Cercopithecus cephus (SIVmus). X-ray crystallography reveals commonalities between SIVmus Vpr and other members of the Vpx/Vpr family with regard to DCAF1 interaction, while cryo-electron microscopy and cross-linking mass spectrometry highlight a divergent molecular mechanism of SAMHD1 recruitment. In addition, these studies demonstrate how SIVmus Vpr exploits the dynamic architecture of the multi-subunit CRL4DCAF1 assembly to optimise SAMHD1 ubiquitylation. Together, the present work provides detailed molecular insight into variability and species-specificity of the evolutionary arms race between host SAMHD1 restriction and lentiviral counteraction through Vpx/Vpr proteins. Author summary Due to the limited size of virus genomes, virus replication critically relies on host cell components. In addition to the host cell’s energy metabolism and its DNA replication and protein synthesis apparatus, the protein degradation machinery is an attractive target for viral re-appropriation. Certain viral factors divert the specificity of host ubiquitin ligases to antiviral host factors, in order to mark them for destruction by the proteasome, to lift intracellular barriers to virus replication. Here, we present molecular details of how the simian immunodeficiency virus accessory protein Vpr interacts with a substrate receptor of host Cullin4-RING ubiquitin ligases, and how this interaction redirects the specificity of Cullin4-RING to the antiviral host factor SAMHD1. The studies uncover the mechanism of Vpr-induced SAMHD1 recruitment and subsequent ubiquitylation. Moreover, by comparison to related accessory proteins from other immunodeficiency virus species, we illustrate the surprising variability in the molecular strategies of SAMHD1 counteraction, which these viruses adopted during evolutionary adaptation to their hosts. Lastly, our work also provides deeper insight into the inner workings of the host’s Cullin4-RING ubiquitylation machinery.
Monkey V1 epidural field potentials provide significant information about stimulus location, size, shape, and color

Brain signal recordings with epidural microarrays constitute a low-invasive approach for recording distributed neuronal signals. Epidural field potentials (EFPs) may serve as a safe and highly beneficial signal source for a variety of research questions arising from both basic and applied neuroscience. A wider use of these signals, however, is constrained by a lack of data on their specific information content. Here, we make use of the high spatial resolution and the columnar organization of macaque primary visual cortex (V1) to investigate whether and to what extent EFP signals preserve information about various visual stimulus features. Two monkeys were presented with different feature combinations of location, size, shape, and color, yielding a total of 375 stimulus conditions. Visual features were chosen to access different spatial levels of functional organization. We found that, besides being highly specific for locational information, EFPs were significantly modulated by small differences in size, shape, and color, allowing for high stimulus classification rates even at the single-trial level. The results support the notion that EFPs constitute a low-invasive, highly beneficial signal source for longer-term recordings for medical and basic research by showing that they convey significant and reliable information about constituent features of activating stimuli.
Placebo Analgesia Does Not Reduce Empathy for Naturalistic Depictions of Others’ Pain in a Somatosensory Specific Way

Empathy for pain involves the affective-motivational and sensory-discriminative pain network. The shared representations account postulates that sharing another’s pain recruits underlying brain functions also engaged during first-hand pain. Critically, causal evidence for this has only been shown for affective pain processing, while the specific contribution of one’s own somatosensory system to empathy remains controversial. Experimental paradigms used in previous studies did not a) direct attention towards a specific body part or b) employed naturalistic depictions of others’ pain, which could explain the absence of somatosensory effects. In this preregistered fMRI study, we thus aimed to test whether a causal manipulation of first-hand pain affects processing of empathy in a somatotopically- matched manner. Forty-five participants underwent a placebo analgesia induction in the right hand and observed pictures of right vs. left hands in pain. We found neither behavioral nor neural evidence for laterality-specific modulation of empathy for pain. However, exploratory analyses revealed a general effect of the placebo on empathy, and higher brain activity in bilateral anterior insula when viewing others’ hands in pain corresponding to one’s own placebo hand. These results refine our knowledge regarding the mechanisms underlying empathy for pain by specifying the influence of first-hand pain on empathic responding.
Effect of Cholesterol on Membrane Partitioning Dynamics of Hepatitis A Virus-2B peptide

Understanding the viral peptide detection, partitioning and subsequent host membrane composition-based response is required for gaining insights into viral mechanism. Here, we probe the crucial role of presence of membrane lipid packing defects, depending on the membrane composition, in allowing the viral peptide belonging to C-terminal Hepatitis A Virus-2B (HAV-2B) to detect, attach and subsequently partition into the host cell membrane mimics. We conclusively show that the hydrophobic residues in the viral peptide detect the transiently present lipid packing defects, insert themselves into such defects, form anchor points and facilitate the partitioning of the peptide. We also show that the presence of cholesterol significantly alters such lipid packing defects, both in size and in number, thus mitigating the partitioning of the membrane active viral peptide into cholesterol-rich membranes. These results show differential ways in which presence and absence of cholesterol can alter the permeability of the host membranes to the membrane active viral peptide component of HAV-2B virus, via lipid packing defects, and can possibly be a part of general membrane detection mechanism for the viroporin class of viruses.
Overexpression of the microtubule-binding protein CLIP-170 induces a +TIP network superstructure consistent with a biomolecular condensate

Proper regulation of microtubule (MT) dynamics is critical for cellular processes including cell division and intracellular transport. Plus-end tracking proteins (+TIPs) dynamically track growing MTs and play a key role in MT regulation. +TIPs participate in a complex web of intra- and inter-molecular interactions known as the +TIP network. Hypotheses addressing the purpose of +TIP:+TIP interactions include relieving +TIP autoinhibition and localizing MT regulators to growing MT ends. In addition, we have proposed that the web of +TIP:+TIP interactions has a physical purpose, creating a superstructure that constrains the structural fluctuations of the fragile MT tip and thus acts as a polymerization chaperone. Many animal +TIP network proteins are multivalent and have intrinsically disordered regions, features commonly found in biomolecular condensates. This observation suggests that the +TIP network might under some conditions form a biomolecular condensate. Previous studies have shown that overexpression of the +TIP CLIP-170 induces large “patch” structures containing CLIP-170 and other +TIPs. To test the hypothesis that these patches might be biomolecular condensates, we used video microscopy, immunofluorescence staining, and Fluorescence Recovery After Photobleaching (FRAP). Our data show that the CLIP-170-induced patches have hallmarks indicative of a biomolecular condensate, one that contains +TIP proteins and excludes other known condensate markers. Moreover, bioinformatic studies demonstrate that the presence of intrinsically disordered regions is conserved in key +TIPs, implying that these regions are functionally significant. Together, these results indicate that the CLIP-170 induced patches in cells are phase-separated liquid condensates and raise the possibility that the endogenous +TIP network might form a liquid droplet at MT ends or other +TIP locations.
Joint Trajectory Inference for Single-cell Genomics Using Deep Learning with a Mixture Prior

Trajectory inference methods are essential for analyzing the developmental paths of cells in single-cell sequencing datasets. It provides insights into cellular differentiation, transitions, and lineage hierarchies, helping unravel the dynamic processes underlying development, disease progression, and tissue regeneration. However, many existing tools for trajectory inference lack a cohesive statistical model and reliable uncertainty quantification, limiting their utility and robustness. In this paper, we introduce VITAE (Variational Inference for Trajectory by AutoEncoder), a novel statistical approach that integrates a latent hierarchical mixture model with variational autoencoders to infer trajectories. The statistical hierarchical model underpinning the approach enhances interpretability, facilitating the exploration of differential gene expression patterns along the trajectory, while the posterior approximations generated by the variational autoencoder ensure computational efficiency, flexibility, and scalability. Notably, VITAE uniquely enables simultaneous trajectory inference and data integration across multiple datasets, enhancing accuracy in both tasks. We show that VITAE outperforms other state-of-the-art trajectory inference methods on both real and synthetic data under various trajectory topologies. Furthermore, we apply VITAE to jointly analyze three distinct single-cell RNA sequencing datasets of the mouse neocortex, unveiling comprehensive developmental lineages of projection neurons. VITAE effectively mitigates batch effects within and across datasets, aligning cells to elucidate clear trajectories and uncover finer structures that might be overlooked in individual datasets. Additionally, we showcase VITAE’s efficacy in integrative analyses of multi-omic datasets with continuous cell population structures.
Mitochondrial introgression by ancient admixture between two distant lacustrine fishes in Sulawesi Island

Sulawesi, an island located in a biogeographical transition zone between Indomalaya and Australasia, is famous for its high levels of endemism. Ricefishes (family Adrianichthyidae) are an example of taxa that have uniquely diversified on this island. It was demonstrated that habitat fragmentation due to the Pliocene juxtaposition among tectonic subdivisions of this island was the primary factor that promoted their divergence; however, it is also equally probable that habitat fusions and resultant admixtures between phylogenetically distant species may have frequently occurred. Previous studies revealed that some individuals of Oryzias sarasinorum endemic to a tectonic lake in central Sulawesi have mitochondrial haplotypes that are similar to the haplotypes of O. eversi, which is a phylogenetically related but geologically distant (ca. 190 km apart) adrianichthyid endemic to a small lake. In this study, we tested if this reflects ancient admixture of O. eversi and O. sarasinorum. Population genomic analyses of genome-wide single-nucleotide polymorphisms revealed that O. eversi and O. sarasinorum are substantially reproductively isolated from each other. Comparison of demographic models revealed that the models assuming ancient admixture from O. eversi to O. sarasinorum was more supported than the models assuming no admixture; this supported the idea that the O. eversi-like mitochondrial haplotype in O. sarasinorum was introgressed from O. eversi. This study is the first to demonstrate ancient admixture of lacustrine organisms in Sulawesi beyond 100 km. The complex geological history of this island enabled such island-wide admixture of lacustrine organisms, which usually experience limited migration.
Squid: Simplifying Quantitative Imaging Platform Development and Deployment

With rapid developments in microscopy methods, highly versatile, robust and affordable implementations are needed to enable rapid and wide adoption by the biological sciences community. Here we report Squid, a quantitative imaging platform with a full suite of hardware and software components and configurations for deploying facility-grade widefield microscopes with advanced features like flat field fluorescence excitation, patterned illumination and tracking microscopy, at a fraction of the cost of commercial solutions. The open and modular nature (both in hardware and in software) lowers the barrier for deployment, and importantly, simplifies development, making the system highly configurable and experiments that can run on the system easily programmable. Developed with the goal of helping translate the rapid advances in the field of microscopy and microscopy-enabled methods, including those powered by deep learning, we envision Squid will simplify roll-out of microscopy-based applications - including at point of care and in low resource settings, make adoption of new or otherwise advanced techniques easier, and significantly increase the available microscope-hours to labs.
Bulkhead-like apical membrane structures between hepatocytes are required for anisotropic lumen expansion and liver tissue morphogenesis

Cell polarity is key to epithelial organization. Whereas polarized epithelial cells have a single apico-basal axis, hepatocytes exhibit a complex multi-axial polarity. During development, the apical surfaces of hepatocytes elongate anisotropically, generating a 3D tubular network of bile canaliculi (BC). Here, to elucidate the mechanisms of hepatocyte polarity and re-engineer it into simple epithelial polarity, we optimised a culture system of primary mouse hepatoblasts that recapitulates hepatocyte differentiation and BC morphogenesis. Remarkably, we discovered a pattern of specific extensions of the apical membrane sealed by tight junctions traversing the lumen between two adjacent hepatocytes that remind the bulkheads of boats. These apical bulkheads were observed also in the developing liver. Screening for molecular factors required for hepatocyte polarity revealed that silencing of Rab35 caused loss of the bulkheads, conversion into simple polarity, formation of cyst-like structures and change in cell fate. By exploiting Rab35 depletion in the developing liver we could re-engineer hepatocyte polarity and trigger formation of epithelial tubes. Our results suggest a new model of BC morphogenesis based on mechanical stabilization of the tubular lumen.