Miracle-dz/UniFAR-FTUs huggingface dataset:
Aging the brain: multi-region methylation principal component based clock in the context of Alzheimer’s disease

Alzheimer’s disease (AD) risk increases exponentially with age and is associated with multiple molecular hallmarks of aging, one of which is epigenetic alterations. Epigenetic age predictors based on 5’ cytosine methylation (DNAm) have previously suggested that biological age acceleration may occur in AD brain tissue. To further investigate brain epigenetic aging in AD, we generated a novel age predictor termed PCBrainAge that was trained solely in cortical samples. This predictor utilizes a combination of principal components analysis and regularized regression, which reduces technical noise and greatly improves test-retest reliability. For further testing, we generated DNAm data from multiple brain regions in a sample from the Religious Orders Study and Rush Memory & Aging Project. PCBrainAge captures meaningful heterogeneity of aging, calculated according to an individual’s age acceleration beyond expectation. Its acceleration demonstrates stronger associations with clinical AD dementia, pathologic AD, and APOE ε4 carrier status compared to extant epigenetic age predictors. It does so across multiple cortical and subcortical regions. Overall, PCBrainAge is useful for investigating heterogeneity in brain aging, as well as epigenetic alterations underlying AD risk and resilience.
Fertilizer reduction with bio-organic fertilizer to regulate the root soil microbial community structure to improve Baby Chinese cabbage yield

Using high-throughput sequencing, this study aimed to explore the response of soil microbial community and Baby Chinese cabbage yield to the reduction of chemical fertilizers combined with bio-organic fertilizer in the Gansu plateau, China. Our experiments consisted of conventional fertilizer (CK), 30% chemical fertilizer reduction + 6,000 kg bio-organic fertilizer (T1), 30% chemical fertilizer reduction + 9,000 kg bio-organic fertilizer (T2), 40% chemical fertilizer reduction + 6,000 kg bio-organic fertilizer (T3), and 40% chemical fertilizer reduction + 9,000 kg bio-organic fertilizer (T4). Compared with CK, soil microbial diversity and richness were higher for all treatments with added bio-organic fertilizer. PCoA showed that the bacterial and fungal communities in T2 and T4 were similar to each other. Redundancy and Spearman’s correlation analyses of microbial communities and soil physicochemical properties revealed that reductions in chemical fertilizer rate combined with bio-organic fertilizer had a stronger impact on the fungal than the bacterial community. They also increased the relative abundance of the dominant bacterial and fungal phyla. Baby Chinese cabbage yield was relatively higher under the combined bio-organic fertilizer plus reduced chemical fertilizer rate with T2 showing the highest yield. Therefore, this approach is feasible for sustainable agricultural, cost-effective and profitable crop production. Importance Bio-organic + moderately reduced chemical fertilizer raised Chinese cabbage yield Bio-organic + chemical fertilizer was more efficacious than either one alone Presence of bio-organic fertilizer enhanced overall rhizosphere physicochemistry Bio-organic fertilizer improved beneficial bacterial & fungal abundance & diversity Fertilizer combination sustainably & cost-effectively improves crop & soil quality
Impact of Fungal Hyphae on Growth and Dispersal of Obligate Anaerobic Bacteria in Aerated Habitats

Although a few studies have reported on the presence of anoxic microniches in fungal biofilms, knowledge of the effects of fungal oxygen consumption on bacterial-fungal interactions is limited. Here, we demonstrate the existence and persistence of oxygen-free zones in air-exposed mycelia enabling spore germination, growth, fermentative activity, and dispersal of the obligate anaerobe. ABSTRACT Anoxic microsites arising in fungal biofilms may foster the presence of obligate anaerobes. Here, we analyzed whether and to which degree hyphae of Coprinopsis cinerea thriving in oxic habitats enable the germination, growth, and dispersal of the obligate anaerobic soil bacterium Clostridium acetobutylicum. Time-resolved optical oxygen mapping, microscopy, and metabolite analysis revealed the formation and persistence of anoxic circum hyphal niches, allowing for spore germination, growth, and fermentative activity of the obligate anaerobe in an otherwise inhabitable environment. Hypoxic liquid films containing 80% ± 10% of atmospheric oxygen saturation around single air-exposed hyphae thereby allowed for efficient clostridial dispersal amid spatially separated (>0.5 cm) anoxic sites. Hyphae hence may serve as good networks for the activity and spatial organization of obligate anaerobic bacteria in oxygenated heterogeneous environments such as soil. IMPORTANCE Although a few studies have reported on the presence of anoxic microniches in fungal biofilms, knowledge of the effects of fungal oxygen consumption on bacterial-fungal interactions is limited. Here, we demonstrate the existence and persistence of oxygen-free zones in air-exposed mycelia enabling spore germination, growth, fermentative activity, and dispersal of the obligate anaerobe. Our study points out a previously overlooked role of aerobic fungi in creating and bridging anoxic microniches in ambient oxic habitats. Air-exposed hyphae hence may act as a scaffold for activity and dispersal of strictly anaerobic microbes. Given the short-term tolerance of strict anaerobes to oxygen and reduced oxygen content in the mycosphere, hyphae can promote spatial organization of both obligate anaerobic and aerobic bacteria. Such finding may be important for a better understanding of previously observed co-occurrences of aerobes and anaerobes in well-aerated habitats such as upland soils.
Systematic hyper-variation and evolution at a lipopolysaccharide locus in the population of Xanthomonas species that infect rice and sugarcane

Advent of high throughput sequencing and population genomics is enabling researchers to investigate selection pressure at hyper-variable genomic loci encoding pathogen-associated molecular patter (PAMP) molecules like lipopolysaccharide (LPS) in an unprecedented manner. Xanthomonas is a model group of phytopathogenic bacteria that infects host in tissue-specific manner. Our in-depth investigation revealed that the successful emergence of lineages infecting major cereals and grasses like rice, sugarcane, and wheat was mediated by acquisition and later replacement of an ancestral type (BXO8) of LPS cassette by distinct one. In the population of the rice xylem pathogen, X. oryzae pv. oryzae (Xoo), the BXO8 is replaced by a distinct BXO1 type of cassette. Alternatively, in diverse Xanthomonas species that infect sugarcane, the BXO8 ancestral cassette has been replaced by yet another kind of Xvv type of LPS cassette, suggesting convergent evolution at an LPS locus mediated by horizontal gene transfer (HGT) events. Aside from xylem, two closely related lineages of X. oryzae that infect parenchyma tissue of rice and Leersia hexandra grass have acquired an LPS cassette from Xanthomonas pathogens that infect citrus, walnut, and strawberry parenchyma, indicating yet another instance of parallel evolution facilitated by HGT. Our targeted and mega-population-based genome dynamic studies revealed potential role of acquisition of specific types of LPS cassettes in the emergence and evolution of tissue specificity in Xanthomonas. Additional cellular, molecular, genetic, and plant studies will help us figure out how a distinct type of LPS help Xanthomonas pathovars and lineages adapt to parenchyma and xylem tissues.
Magnetoencephalography can reveal deep brain network activities linked to memory processes

Recording from deep neural structures such as hippocampus non-invasively and yet with high temporal resolution remains a major challenge for human neuroscience. Although it has been proposed that deep neuronal activity might be recordable during cognitive tasks using magnetoencephalography (MEG), this remains to be demonstrated as the contribution of deep structures to MEG recordings may be too small to be detected or might be eclipsed by the activity of large-scale neocortical networks. In the present study, we disentangled mesial activity and large-scale networks from the MEG signals thanks to blind source separation (BSS). We then validated the MEG BSS components using intracerebral EEG signals recorded simultaneously in patients during their presurgical evaluation of epilepsy. In the MEG signals obtained during a memory task involving the recognition of old and new images, we identified with BSS a putative mesial component, which was present in all patients and all control subjects. The time course of the component selectively correlated with SEEG signals recorded from hippocampus and rhinal cortex, thus confirming its mesial origin. This finding complements previous studies with epileptic activity and opens new possibilities for using MEG to study deep brain structures in cognition and in brain disorders.
Direct fluorescent labeling of NF186 and NaV1.6 in living primary neurons using bioorthogonal click chemistry

The axon initial segment (AIS) is a highly specialized neuronal compartment that regulates the generation of action potentials and maintenance of neuronal polarity. Despite its importance, live imaging of the AIS is challenging due to the limited number of suitable labeling methods. To overcome this limitation, we established a novel approach for live labeling of the AIS using unnatural amino acids (UAAs) and bioorthogonal click chemistry. The small size of the UAAs and the possibility of introducing them virtually anywhere into the target proteins make this method particularly suitable for live labeling and imaging of complex and spatially restricted proteins. With this approach, we labeled two large AIS components, the 186 kDa isoform of neurofascin (NF186) and the 260 kDa voltage-gated sodium channel (NaV1.6), and performed widefield and confocal microscopy in fixed and living neurons. Moreover, we demonstrated the applicability of this method by studying the localization of two epilepsy-causing NaV1.6 variants with a loss-of-function effect. Finally, to further improve the efficiency of the UAA incorporation, we developed adeno-associated viral (AAV) vectors for click labeling in primary neurons. The use of AAV vectors will facilitate the transfer of UAA-based click labeling technology to more complex biological systems, such as organotypic slice cultures, organoids, and animal models.
Endothelial FOXC1 and FOXC2 promote intestinal regeneration after ischemia–reperfusion injury

Intestinal ischemia induces mucosal damage while simultaneously activating intestinal stem cells (ISCs), which subsequently regenerate the damaged intestinal epithelium. However, whether paracrine factors secreted from vascular endothelial cells (ECs) - blood and lymphatic ECs (BECs and LECs, respectively) – regulate ISC-mediated regeneration have yet to be elucidated. Here, we identify FOXC1 and FOXC2 as essential regulators of paracrine signaling in regeneration of the small intestine after ischemia-reperfusion (I/R) injury. EC- and LEC-specific deletions of Foxc1, Foxc2, or both in mice augment I/R-induced intestinal damage by causing defects in vascular regrowth, expression of the chemokine CXCL12 and the Wnt activator R- spondin 3 in BECs and LECs, respectively, and activation of Wnt signaling in ISCs. Treatment with CXCL12 and R-spondin 3 rescues the I/R-induced intestinal damage in EC- and LEC-Foxc mutant mice, respectively. This study provides evidence that FOXC1 and FOXC2 are required for intestinal regeneration by stimulating paracrine CXCL12 and Wnt signaling.
Feedback inhibition underlies new computational functions of cerebellar interneurons

The function of a feedback inhibitory circuit between cerebellar Purkinje cells and molecular layer interneurons (MLIs) was defined by combining optogenetics, neuronal activity recordings both in cerebellar slices and in vivo, and computational modeling. Purkinje cells inhibit a subset of MLIs in the inner third of the molecular layer. This inhibition is non-reciprocal, short-range (less than 200 μm) and is based on convergence of 1-2 Purkinje cells onto MLIs. During learning-related eyelid movements in vivo, the activity of a subset of MLIs progressively increases at the same time that Purkinje cell activity decreases, with Purkinje cells usually leading the MLIs. Computer simulations indicate that these relationships are best explained by the feedback circuit from Purkinje cells to MLIs and that this feedback circuit plays a central role in making cerebellar learning efficient.
Finite element model updating using strain‐based power spectral density for damage detection

In this paper a new sensitivity‐based finite element (FE) model updating method using spectral density of strain as metric is introduced, which is applicable for damage detection and structural health monitoring purposes. Derivation of the sensitivity equation is exact without any need for approximation. A set of incompletely measured natural frequencies and damping loss factors of the damaged structure is used to deal with incomplete measurement without implementation of the FE model reduction or data expansion algorithms. The insights provided from the distribution of the spectral strain energy among the elements in the intact model are used for selection of excitation location. The solution to the developed sensitivity equation is achieved by linear least square and imposing unprejudiced side constraints on the design variables. The proposed method is successfully examined on the FE model of a 3D truss and frame structure and is capable of localization and quantification of damage. The method is robust against measurement, natural frequency, and mass modeling error. Copyright © 2016 John Wiley & Sons, Ltd.
Exploring the Pharmacological Mechanisms of Xihuang Pills Against Prostate Cancer via Integrating Network Pharmacology and Experimental Validation In Vitro and In Vivo

Background: Drug resistance is the major cause of increasing mortality in prostate cancer (PCa). Therefore, it an urgent to develop more effective therapeutic agents for PCa treatment. Xihuang pills (XHP) have been recorded as the efficient anti-tumor formula in ancient Chinese medical literature, which has been utilized in several types of cancers nowadays. However, the effect protective role of XHP on the PCa and its underlying mechanisms are still unclear. Methods: The active ingredients of XHP were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and BATMAN-TCM. The potential targets of PCa were acquired from the Gene Cards and OMIM databases. R language and Perl language program were utilized to clarify the interaction between the PCa-related targets and the potential targets of XHP. The potential targets of XHP for prostate cancer were gathered from the Gene ontology and KEGG pathway. Furthermore, cell proliferation assays were verified by PC3 and LNCaP cells. The efficacy and potential mechanism tests were confirmed by the PCa PC3 cells and mice subcutaneous transplantation. The effects of PI3K/Akt/mTOR-related proteins on proliferation, apoptosis, and cell cycle of PCa cells were measured by the Cell Counting Kit-8(CCK8), TUNEL assay, real-time quantitative reverse transcription PCR (QRT-PCR), and Western Blotting, respectively. Results: The active components of four traditional Chinese medicines in XHP were searched on the TCMSP and Batman TCM database. The biological active components of XHP were obtained as OB ≥30% and DL ≥0.18. The analysis of gene ontology and KEGG pathway identified the PI3K/Akt/mTOR signaling pathway as the XHP-associated pathway. Collectively, the results of in vitro and in vivo experiments showed that XHP had the effect of inhibiting on the proliferation of PC3 and LNCaP cells. XHP promoted the apoptosis and restrained the cell cycle and invasion of the PC3 cells and subcutaneous transplantation. Meanwhile, the suppression of XHP on the level of expression of PI3K, Akt, and mTOR-pathway-related pathway proteins has been identified in a dose-dependent manner. Conclusion: PI3K/Akt/mTOR pathway-related pathway proteins were confirmed as the potential XHP-associated targets for PCa. XHP can suppress the proliferation of prostate cancer via inhibitions of the PI3K/Akt/mTOR pathway.
Association Between Preonset Anti-hypertensive Treatment and Intracerebral Hemorrhage Mortality: A Cohort Study From CHEERY

Introduction Hypertension is the most prevalent risk factor for intracerebral hemorrhage (ICH). In this study, we investigated whether preonset anti-hypertensive therapy could affect the outcomes of ICH. Methods This was a retrospective cohort study. A total of 3,460 consecutive patients with acute first-ever ICH from 31 recruitment sites were enrolled into the Chinese cerebral hemorrhage: mechanism and intervention (CHERRY) study from December 1, 2018 to November 30, 2020, and 2,140 (61.8%) with hypertension history were entered into the analysis. Results Only 586 patients (27.4%) with hypertension history currently received anti-hypertensive therapy, and which was associated with lower systolic blood pressure (SBP) and diastolic blood pressure (DBP) on admission (SBP, p = 0.008; DBP, p = 0.017), less hematoma volume (9.8 vs. 11%, p = 0.006), and lower all-cause mortality at 3 months (15.3 vs. 19.8%, OR = 0.728, p = 0.016). In multivariable analysis, adjusting for age, gender, residence, ischemic stroke history, admission SBP and DBP, and current use of antihypertension were significantly associated with lower adjusted hazard ratios (HRs) for all-cause mortality at discharge (adjusted HR, 0.497, p = 0.012), 30 days (adjusted HR, 0.712, p = 0.015), and 90 days (adjusted HR, 0.766, p = 0.030). However, after adjusting the variable of hematoma volume, the mortality between the two groups was not significantly different. Conclusions Preonset anti-hypertensive therapy was associated with lower mortality of ICH, which somewhat depended on hematoma volume.
Characterization of Vegetative Incompatibility in Morchella importuna and Location of the Related-Genes by Bulk Segregant Analysis

Vegetative incompatibility (VI) is a widespread phenomenon developed in Morchella importuna, a species of ascomycete fungus that is cultivated on a rapidly expanding scale in China. Understanding the genetic bases of this nonself-recognition phenomenon is beneficial for resolving some problems that are associated with the production of this highly prized edible fungus, such as crossbreeding, strain classification, and pathogen transmission. VI is genetically controlled by het genes, organized in two different systems, namely allelic and nonallelic. These het genes have been well characterized in Podospora anserina and Neurospora crassa. In this work, putative het-homologs were identified in the genome of M. importuna, but their low allelic polymorphism in different vegetative compatibility groups (VCGs) suggested that VI in this fungus might not be regulated by these het genes. The progeny derived from vegetative compatible parents became a VCG, while the single-ascospore strains from vegetative incompatible parents were divided into four VCGs, and the interaction between the inter-group strains led to the formation of two types of barrages, viz., thin dark line and raised aggregate of hyphae. The Bulk Segregant Analysis confirmed that the genes mimpvic32 and mimpvic33 were linked to VI reactions in M. importuna; nevertheless, the formation of barrages also occurred between the pairs carrying the same allele of these two genes. In sum, the VI control system in M. importuna was complicated, and there were more other allelic or non-allelic VI-related genes.
Oral Neutrophil Free Fatty Acid Receptors Expression May Link Oral Host and Microbiome Lipid Metabolism

In health, commensal bacteria from oral biofilms stimulate polymorphonuclear neutrophil (PMN) recruitment in gingival sulci and the oral cavity. Oral PMN (oPMN) is short-lived cells with low prosurvival gene expression. In periodontitis, oPMN accumulates in higher numbers, has extended lifespan, and sustains nonresolving inflammation. We hypothesize that short- and long-chain free fatty acids (SCFAs and LCFAs) and lipid mediator resolvin E1 (RvE1) modulate host ability to control biofilms and resolve inflammation. Our objective was to measure oPMN surface expression of receptors FFAR2 (binds bacteria-derived SCFA), FFAR4 (binds LCFA, EPA, and DHA), and ERV1 (binds RvE1) in health and to assess sex differences. We included 20 periodontally healthy individuals aged 20–80 years (10 males, 10 females), who were asked to (1) answer a targeted health nutritional questionnaire and (2) provide an oral saline rinse. oPMN isolated by sequential filtration was labeled with fluorophore-conjugated antibodies against CD11b, CD14, CD16, CD66b, ERV1, FFAR2, and FFAR4 and analyzed by flow cytometry. Statistical analyses were the following: two-way ANOVA, Tukey's test, and Pearson's correlation. Oral rinses contained 80% oPMN of which 60% were ERV1+ and FFAR2+, and 10% FFAR4+, with no sex differences. Females had more oPMN ERV1 compared to males. Both sexes had higher ERV1 compared to FFAR2 and FFAR4. CD66b+CD16high oPMN expressed less ERV1 and FFAR2 compared to CD66b+CD16low. There were positive correlations between oPMN ERV1 and FFAR2 expression and between ERV1+ and FFAR2+ oPMN and fish intake. These findings will help to better understand how oral host and microbiome interactions maintain periodontal health.
Facial Mask Detection Using Depthwise Separable Convolutional Neural Network Model During COVID-19 Pandemic

Deep neural networks have made tremendous strides in the categorization of facial photos in the last several years. Due to the complexity of features, the enormous size of the picture/frame, and the severe inhomogeneity of image data, efficient face image classification using deep convolutional neural networks remains a challenge. Therefore, as data volumes continue to grow, the effective categorization of face photos in a mobile context utilizing advanced deep learning techniques is becoming increasingly important. In the recent past, some Deep Learning (DL) approaches for learning to identify face images have been designed; many of them use convolutional neural networks (CNNs). To address the problem of face mask recognition in facial images, we propose to use a Depthwise Separable Convolution Neural Network based on MobileNet (DWS-based MobileNet). The proposed network utilizes depth-wise separable convolution layers instead of 2D convolution layers. With limited datasets, the DWS-based MobileNet performs exceptionally well. DWS-based MobileNet decreases the number of trainable parameters while enhancing learning performance by adopting a lightweight network. Our technique outperformed the existing state of the art when tested on benchmark datasets. When compared to Full Convolution MobileNet and baseline methods, the results of this study reveal that adopting Depthwise Separable Convolution-based MobileNet significantly improves performance (Acc. = 93.14, Pre. = 92, recall = 92, F-score = 92).