Miracle-dz/UniFAR-FTUs huggingface dataset:
Metabolic Profiling and Integration of Metabolomic and Transcriptomic Data From Pectoralis Muscle Reveal Winter-Adaptive Metabolic Responses of Black-Capped Chickadee and American Goldfinch

Seasonal changes, such as alterations in food availability or type and cold conditions, present challenges to free-living birds living in highly seasonal climates. Small birds respond to such challenges through seasonal metabolic flexibility, which better matches seasonal metabolic phenotypes to environmental conditions and can improve fitness. To better understand the mechanistic basis of this metabolic flexibility, we conducted a large-scale metabolic profiling of pectoralis muscle in black-capped chickadees (Poecile atricapillus) and American goldfinches (Spinus tristis), which are small, year-round bird species of temperate-zones. We analyzed muscle samples using non-biased, global metabolomics profiling technology based on UHLC/MS/MS2 platforms. A total of 582 metabolites was characterized for summer and winter season samples. Chickadees showed greater seasonal separation of global metabolite profiles than goldfinches, which is consistent with previous transcriptomic studies of pectoralis muscle in these two species. Reduced levels of amino acids during winter occurred in both species and might reflect decreasing dietary protein intake, amino acid shuttling to other pathways for thermogenesis and/or elevated rates of protein turnover in the pectoralis muscle. Concomitant decreased abundances in tricarboxylic acid cycle (TCA) metabolites suggest faster cycling of the oxidative phosphorylation pathway in winter to meet the metabolic demands of thermogenesis. Accordingly, chickadees displayed shifts toward lipid oxidation in winter, whereas goldfinches showed winter declines in ketone bodies, which suggests increased energy demand or subtle changes in substrate availability. Beyond the winter-specific changes in metabolite abundances, integration of the metabolomic and the transcriptomic data revealed a landscape of gene–metabolite associations related to the winter-adaptive metabolic response. This landscape of gene–metabolite pairs was overrepresented by pathways associated with transport of small molecules, metabolism of amino acids and derivatives, activation and biosynthesis of fatty acid derivatives, and biosynthesis and metabolism of nicotinate and nicotinamide derivatives. Collectively, our results suggest that increased levels of NADH and its derivatives in the pectoralis muscle are a potential novel mechanism for increasing winter metabolic output, fueled by lipids, for thermogenesis during winter.
Protective Effect of Purinergic P2X7 Receptor Inhibition on Acrolein-Induced Urothelial Cell Damage

Patients undergoing chemotherapy with cyclophosphamide experience cystitis due to excretion of a toxic metabolite, acrolein. Cystitis, an inflammation of the bladder, is associated with damage to the integrity of the urothelial barrier. The purinergic P2X7 receptor (P2X7R) is increasingly recognized for its role in inflammation and cell death. P2X7R is expressed abundantly on the bladder urothelium. The aim of this study was to investigate the role of P2X7R in acrolein-induced inflammatory damage in primary cultured porcine bladder urothelial cells. Confluent urothelial cells in culture were treated with acrolein to induce damage; also, with the P2X7R selective antagonist, A804598. Cell viability assay, immunocytochemistry, and trans-epithelial electrical resistance (TEER) studies were carried out to investigate the effect of treatments on urothelial cell function. Acrolein induced a significant reduction in urothelial cell viability, which was protected by the presence of A804598 (10 µM). The urothelial barrier function, indicated by TEER values, was also significantly reduced by acrolein, whereas pre-incubation with P2X7R antagonist significantly protected the urothelial cell barrier from acrolein-induced TEER reduction. The structure of urothelial cell tight junctions was similarly impacted by acrolein treatment, showing the fragmentation of zona occludens-1 (ZO-1) immunoreactivity. Pre-treatment of cells with A804598 countered against the actions of acrolein and maintained ZO-1 expression level and cell structure. The damaging effect of acrolein on urothelial cells integrity could be impaired by inhibition of P2X7R, therefore P2X7R blockade may be a possible therapy in patients with bladder cystitis caused by cyclophosphamide treatment.
Mechanism of Overlying Strata Migration and Failure During Underground Mining in the Mountainous Carbonate Areas in Southwestern China

In this study, theoretical analysis and numerical simulation methods were used to investigate the mechanical mechanism of the migration failure of the overlying strata and the development characteristics of the water-conducting fractured zone (WCFZ) in the mountainous carbonate areas in southwestern China. Due to the block-shaped rock mass structure characteristics of carbonate rocks, this paper considered the rock mass structure of the overlying strata. For the three-hinged arch structure of the block-shaped rock mass, the theory of damage mechanics was used to deduct the recursive calculation formula for the ultimate subsidence of the three-hinged arch structure of the overlying strata. Then, a method for determining the height of the WCFZ (HWCFZ) in the overlying strata under mining conditions was developed. Numerical simulations were carried out to study the stress field, plastic zone, and displacement field of the overlying strata and the dynamic evolution of the WCFZ during the mining process, and it was revealed that there was a positive feedback effect between them. After the mine was mined, due to the change of the stress field of the overlying strata, the overlying strata were mainly subjected to three types of plastic deformation during the fracturing process: tension, shearing, and tensile-shearing. There was a plastic partitioning phenomenon in the overlying strata. Among them, the tensile-slip failure zone was the most severely damaged. And the boundary of the WCFZ and the bending subsidence zone were determined based on the change characteristics of the displacement field. The HWCFZ obtained from the numerical simulations was consistent with the theoretical calculated value (93 vs. 92.5 m), validating the reliability and accuracy of the theoretical calculation method. Underground mining activities are active in the mountainous carbonate areas in southwestern China, and there are many landslide disasters due to overlying strata collapse, resulting in serious casualties. Therefore, prediction of HWCFZ and stability analysis of mountain need to be carried out for different mines in order to effectively carry out geological disaster prevention and mitigation research.
The Time Course of Monocytes Infiltration After Acoustic Overstimulation

Cochlea macrophages regulate cochlea inflammation and may harbors the potentials to protect hearing function from injury, including acoustic overstimulation. Cochlea macrophage numbers increase at 3–7 days after acoustic stimulation. However, the exact timing of macrophage infiltration and maturation from inflammatory monocytes is unclear. Furthermore, neutrophils may also be involved in this process. Therefore, in this study, we investigated time-dependent immune cell infiltration, macrophage transformation, and neutrophil involvement following acoustic stimulation. Flow cytometry and immunofluorescence were conducted in C-X3-C motif chemokine receptor 1 (CX3CR1)+/GFP mice after acoustic overstimulation (at baseline and at 1, 2, 3, and 5 days after exposure to 120 dB for 1 h) to identify inflammatory monocytes in the cochlea. RNA-sequencing and quantitative polymerase chain reaction were performed to identify differentially expressed genes. Inflammatory monocytes infiltrated into the lower portion of the lateral wall within 2 days after acoustic overstimulation (dpn), followed by transformation into macrophages at 3–5 dpn via CX3CR1 upregulation and Ly6C downregulation. In addition, inflammatory monocytes were aggregated inside the collecting venule only at 1 dpn. Neutrophils were not a major type of phagocyte during this response. The gene encoding C-C motif chemokine ligand 2 gene was significantly upregulated as early as 3 h after acoustic overstimulation. Given these results, treatment to control immune response after a noise-induced hearing loss should be applied as soon as possible.
Association of Homocysteine Levels With Medial Temporal Lobe Atrophy Among Carriers and Non-carriers of APOE ε4 in MCI Subjects

Background Different clinical subtypes of mild cognitive impairment (MCI) involve heterogeneous underlying etiologies. This study investigated the association between demographics, neuropsychological performance, apolipoprotein E (APOE) genotype and magnetic resonance imaging (MRI) measures in patients with MCI (amnestic [aMCI] and non-amnestic [naMCI]). Methods This case–control study included 130 aMCI patients, 58 naMCI patients, and 1,106 healthy controls (HCs). APOE genotypes, medial temporal lobe atrophy (MTA), neurological evaluation results, and white matter hyperintensities (WMH) were investigated. Serum folate and vitamin B12 concentrations were analyzed by radioimmunoassay, and plasma hyperhomocysteinemia (Hcy) was assessed by a high-performance liquid chromatography-fluorescence method. Results Serum folate levels were significantly lower, but plasma Hcy levels were higher, in patients with aMCI and naMCI than in healthy controls. There were significantly higher MTA scores in the aMCI group than the healthy control group. Multiple linear regression showed that serum Hcy and folate concentrations were positively associated with MTA (p < 0.05), while APOE4 showed a significant negative association with MTA in the aMCI group (p < 0.01). In addition, moderate/severe WMH showed a significant negative association with MTA in the naMCI and HC groups (p < 0.01). Conclusion The combined presence of APOE4 and Hcy is associated with aMCI in elderly individuals, while moderate/severe WMH is related to naMCI, which suggests etiological differences across MCI subtypes.
Arabidopsis Novel Microgametophyte Defective Mutant 1 Is Required for Pollen Viability via Influencing Intine Development in Arabidopsis

The pollen intine layer is necessary for male fertility in flowering plants. However, the mechanisms behind the developmental regulation of intine formation still remain largely unknown. Here, we identified a positive regulator, Arabidopsis novel microgametophyte defective mutant 1 (AtNMDM1), which influences male fertility by regulating intine formation. The AtNMDM1, encoding a pollen nuclei-localized protein, was highly expressed in the pollens at the late anther stages, 10–12. Both the mutations and the knock-down of AtNMDM1 resulted in pollen defects and significantly lowered the seed-setting rates. Genetic transmission analysis indicated that AtNMDM1 is a microgametophyte lethal gene. Calcofluor white staining revealed that abnormal cellulose distribution was present in the aborted pollen. Ultrastructural analyses showed that the abnormal intine rather than the exine led to pollen abortion. We further found, using transcriptome analysis, that cell wall modification was the most highly enriched gene ontology (GO) term used in the category of biological processes. Notably, two categories of genes, Arabinogalactan proteins (AGPs) and pectin methylesterases (PMEs) were greatly reduced, which were associated with pollen intine formation. In addition, we also identified another regulator, AtNMDM2, which interacted with AtNMDM1 in the pollen nuclei. Taken together, we identified a novel regulator, AtNMDM1 that affected cellulose distribution in the intine by regulating intine-related gene expression; furthermore, these results provide insights into the molecular mechanisms of pollen intine development.
Peptide-Grafted Microspheres for Mesenchymal Stem Cell Sorting and Expansion by Selective Adhesion

Mesenchymal stem cells (MSCs) have considerable value in regenerative medicine because of their unique properties such as pluripotency, self-renewal ability, and low immunogenicity. Isolation and purification are prerequisites for various biomedical applications of MSCs, and traditional sorting methods are often expensive, complicated, and difficult to apply on a large scale. In addition to purification, the requirement for expansion of cells also limits the further application of MSCs. The purpose of this study was to develop a unique magnetic sorting microsphere to obtain relatively pure and high-yield MSCs in an economical and effective way, that can also be used for the expansion of MSCs. Poly (ethylene glycol) (PEG)-based anti-adhesive treatment of the prepared oleic acid grafted Fe3O4-poly (lactic-co-glycolic acid) magnetic microspheres was performed, and then E7 peptide was covalently grafted onto the treated microspheres. Upon a series of characterization, the magnetic microspheres were of uniform size, and cells were unable to adhere to the PEG-treated surface. E7 grafting significantly improved cell adhesion and proliferation. The results obtained from separate culture of various cell types as well as static or dynamic co-culture showed that selective adhesion of MSCs was observed on the magnetic sorting microspheres. Furthermore, the cells expanded on the microspheres maintained their phenotype and typical differentiation potentials. The magnetic properties of the microspheres enabled sampling, distribution, and transfer of cells without the usage of trypsin digestion. And it facilitated the separation of cells and microspheres for harvesting of MSCs after digestion. These findings have promising prospects for MSC research and clinical applications.
Fungal Inhibition of Agricultural Soil Pathogen Stimulated by Nitrogen-Reducing Fertilization

Plant health is the fundamental of agricultural production, which is threatened by plant pathogens severely. The previous studies exhibited the effects of different pathogen control strategies (physical, chemical, and microbial methods), which resulted from bringing in exogenous additives, on microbial community structures and functions. Nevertheless, few studies focused on the potential inhibitory abilities of native microbial community in the soil, which could be activated or enhanced by different fertilization strategies. In this study, three plant diseases (TMV, TBS, and TBW) of tobacco, fungal community of tobacco rhizosphere soil, and the correlation between them were researched. The results showed that nitrogen-reducing fertilization strategies could significantly decrease the occurrence rate and the disease index of three tobacco diseases. The results of bioinformatics analyses revealed that the fungal communities of different treatments could differentiate the nitrogen-reducing fertilization group and the control group (CK). Furthermore, key genera which were responsible for the variation of fungal community were explored by LEfSe analysis. For instance, Tausonia and Trichocladium increased, while Naganishia and Fusicolla decreased under nitrogen-reducing fertilization conditions. Additionally, the correlation between tobacco diseases and key genera was verified using the Mantel test. Moreover, the causal relationship between key genera and tobacco diseases was deeply explored by PLS–PM analysis. These findings provide a theoretical basis for a nitrogen-reducing fertilization strategy against tobacco diseases without exogenous additives and make contributions to revealing the microbial mechanism of native-valued fungal key taxa against tobacco diseases, which could be stimulated by agricultural fertilization management.
Optimizing the Boosting Schedule of Subunit Vaccines Consisting of BCG and “Non-BCG” Antigens to Induce Long-Term Immune Memory

Boosting Bacillus Calmette-Guérin (BCG) with subunit vaccine is expected to induce long-term protection against tuberculosis (TB). However, it is urgently needed to optimize the boosting schedule of subunit vaccines, which consists of antigens from or not from BCG, to induce long-term immune memory. To address it two subunit vaccines, Mtb10.4-HspX (MH) consisting of BCG antigens and ESAT6-CFP10 (EC) consisting of antigens from the region of difference (RD) of Mycobacterium tuberculosis (M. tuberculosis), were applied to immunize BCG-primed C57BL/6 mice twice or thrice with different intervals, respectively. The long-term antigen-specific immune responses and protective efficacy against M. tuberculosis H37Ra were determined. The results showed that following BCG priming, MH boosting twice at 12-24 weeks or EC immunizations thrice at 12-16-24 weeks enhanced the number and function of long-lived memory T cells with improved protection against H37Ra, while MH boosting thrice at 12-16-24 weeks or twice at 8-14 weeks and EC immunizations twice at 12-24 weeks or thrice at 8-10-14 weeks didn’t induce long-term immunity. It suggests that following BCG priming, both BCG antigens MH boosting twice and “non-BCG” antigens EC immunizations thrice at suitable intervals induce long-lived memory T cell-mediated immunity.
Tuina for Enuresis in Children: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objective To evaluate the effects of Tuina (massage) vs. non-Tuina traditional Chinese medicine (TCM) treatments on nocturnal enuresis in children. Methods A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted following the Preferred Reported Items for Systematic Review and Meta-analysis (PRISMA) guidelines. RevMan 5.3 software was used for meta-analysis. Results Twelve RCTs recruiting a total of 1,007 children were included. Meta-analysis results showed that, compared with non-Tuina TCM treatments, Tuina could significantly improve the total effective rate of children's enuresis [RR = 1.29, 95%CI (1.22–1.36), P < 0.00001]. The results of subgroup analyses indicated that the total effective rate of Tuina combined with acupuncture in the treatment of nocturnal enuresis was higher than acupuncture alone [RR = 1.24, 95%CI (1.12–1.37), P < 0.0001]. The total effective rate of Tuina in the treatment of enuresis in children was better than that of herbal medicine alone [RR = 1.45, 95%CI (1.31–1.61), P < 0.00001]. The total effective rate of Tuina combined with herbal medicine in the treatment of enuresis in children was better than that of herbal medicine alone [RR = 1.16, 95%CI (1.06–1.26), P = 0.0007]. No adverse reactions of Tuina were reported in all included studies. Conclusion From the available evidence, Tuina, or Tuina combined with non-Tuina TCM treatments (acupuncture, or herbal medicine) can improve the clinical outcome of children with enuresis, indicating Tuina is a promising treatment choice for children's enuresis. However, because of the intrinsic limitations of the included studies, more high-quality randomized controlled trials with longer follow-up are still needed to further confirm the efficacy and safety of Tuina in the treatment of nocturnal enuresis in children.
Self-Ascribed Paranormal Ability: Reflexive Thematic Analysis

This study investigated personal perceptions (involvements) and comprehensions (interpretations) of self-ascribed paranormal abilities. Twelve participants with supposed supernatural powers took part in semi-structured interviews exploring the origin, phenomenology, and nature of their powers. Interview transcripts were analysed using reflexive thematic analysis (RTA), a qualitative method that identifies patterns within data. Four major themes expressed meanings and representations held by participants: Formative Influences (sub-themes: Gifted Family Members and Anomalous Occurrence), (Inter) Subjective Paranormal Experience (sub-themes: Transcendental/Mystic and Extra-Sensory Perception), Embodied Processes (sub-theme: Control), and Perception of Reality (two sub-themes: Self-Awareness and Fantastic/Surreal Perceptions). Consideration of themes identified an inextricable link between perception, interpretation, and belief in ability. Within narratives, interviewees outlined, contextualised, and established the validity of their powers. They drew upon supporting autobiographical evidence from their life histories and obfuscated and/or discounted conventional explanations. Generally, accounts reflected individual attempts to comprehend and justify the nature and experience of professed abilities. The authors discuss these processes and suggest ways to extend and develop ensuing research.
Insights Into Drug Repurposing, as Well as Specificity and Compound Properties of Piperidine-Based SARS-CoV-2 PLpro Inhibitors

The COVID-19 pandemic continues unabated, emphasizing the need for additional antiviral treatment options to prevent hospitalization and death of patients infected with SARS-CoV-2. The papain-like protease (PLpro) domain is part of the SARS-CoV-2 non-structural protein (nsp)-3, and represents an essential protease and validated drug target for preventing viral replication. PLpro moonlights as a deubiquitinating (DUB) and deISGylating enzyme, enabling adaptation of a DUB high throughput (HTS) screen to identify PLpro inhibitors. Drug repurposing has been a major focus through the COVID-19 pandemic as it may provide a fast and efficient route for identifying clinic-ready, safe-in-human antivirals. We here report our effort to identify PLpro inhibitors by screening the ReFRAME library of 11,804 compounds, showing that none inhibit PLpro with any reasonable activity or specificity to justify further progression towards the clinic. We also report our latest efforts to improve piperidine-scaffold inhibitors, 5c and 3k, originally developed for SARS-CoV PLpro. We report molecular details of binding and selectivity, as well as in vitro absorption, distribution, metabolism and excretion (ADME) studies of this scaffold. A co-crystal structure of SARS-CoV-2 PLpro bound to inhibitor 3k guides medicinal chemistry efforts to improve binding and ADME characteristics. We arrive at compounds with improved and favorable solubility and stability characteristics that are tested for inhibiting viral replication. Whilst still requiring significant improvement, our optimized small molecule inhibitors of PLpro display decent antiviral activity in an in vitro SARS-CoV-2 infection model, justifying further optimization.