Admission blood tests predicting survival of SARS-CoV-2 infected patients: a practical implementation of graph convolution network in imbalance dataset.

BACKGROUND: Predicting an individual's risk of death from COVID-19 is essential for planning and optimising resources. However, since the real-world mortality rate is relatively low, particularly in places like Hong Kong, this makes building an accurate prediction model difficult due to the imbalanced nature of the dataset. This study introduces an innovative application of graph convolutional networks (GCNs) to predict COVID-19 patient survival using a highly imbalanced dataset. Unlike traditional models, GCNs leverage structural relationships within the data, enhancing predictive accuracy and robustness. By integrating demographic and laboratory data into a GCN framework, our approach addresses class imbalance and demonstrates significant improvements in prediction accuracy. METHODS: The cohort included all consecutive positive COVID-19 patients fulfilling study criteria admitted to 42 public hospitals in Hong Kong between January 23 and December 31, 2020 (n = 7,606). We proposed the population-based graph convolutional neural network (GCN) model which took blood test results, age and sex as inputs to predict the survival outcomes. Furthermore, we compared our proposed model to the Cox Proportional Hazard (CPH) model, conventional machine learning models, and oversampling machine learning models. Additionally, a subgroup analysis was performed on the test set in order to acquire a deeper understanding of the relationship between each patient node and its neighbours, revealing possible underlying causes of the inaccurate predictions. RESULTS: The GCN model was the top-performing model, with an AUC of 0.944, considerably outperforming all other models (p < 0.05), including the oversampled CPH model (0.708), linear regression (0.877), Linear Discriminant Analysis (0.860), K-nearest neighbours (0.834), Gaussian predictor (0.745) and support vector machine (0.847). With Kaplan-Meier estimates, the GCN model demonstrated good discriminability between low- and high-risk individuals (p < 0.0001). Based on subanalysis using the weighted-in score, although the GCN model was able to discriminate well between different predicted groups, the separation was inadequate between false negative (FN) and true negative (TN) groups. CONCLUSION: The GCN model considerably outperformed all other machine learning methods and baseline CPH models. Thus, when applied to this imbalanced COVID survival dataset, adopting a population graph representation may be an approach to achieving good prediction.

Hyperbaric oxygen therapy attenuates heatstroke-induced hippocampal injury by inhibiting microglial pyroptosis.

Background: Central nervous system (CNS) injury is the most prominent feature of heatstroke and the hippocampus is prone to damage. However, the mechanisms underlying the heatstroke-induced hippocampal injury remain unclear. Hyperbaric oxygen (HBO) therapy prevents CNS injury in heatstroke mice. However, the underlying mechanisms of HBO in heatstroke-induced hippocampal injury remain unclear. This study aimed to elucidate the protective effects of HBO against hippocampal injury and its potential role in microglial pyroptosis in heatstroke rats.Methods: A rat heatstroke model and a heat stress model with a mouse microglial cell line (BV2) were, respectively, used to illustrate the effect of HBO on heat-induced microglial pyroptosis in vivo and in vitro. We used a combination of molecular and histological methods to assess microglial pyroptosis and neuroinflammation both in vivo and in vitro.Results: The results revealed that HBO improved heatstroke-induced survival outcomes, hippocampal injury, and neurological dysfunction in rats. In addition, HBO mitigates microglial pyroptosis and reduces the expression of pro-inflammatory cytokines in the hippocampus of heatstroke rats. In vitro experiments showed that HBO attenuated BV2 cell injury under heat stress. Furthermore, HBO prevented heat-induced pyroptosis of BV2 cells, and the expression of pro-inflammatory cytokines IL-18 and IL-1ß was reduced. Mechanistically, HBO alleviates heatstroke-induced neuroinflammation and hippocampal injury by preventing microglial pyroptosis. Conclusions: In conclusion, HBO attenuates heatstroke-induced neuroinflammation and hippocampal injury by inhibiting microglial pyroptosis.

Ultra-low-field magnetization transfer imaging at 0.055T with low specific absorption rate.

PURPOSE: To demonstrate magnetization transfer (MT) effects with low specific absorption rate (SAR) on ultra-low-field (ULF) MRI. METHODS: MT imaging was implemented by using sinc-modulated RF pulse train (SPT) modules to provide bilateral off-resonance irradiation. They were incorporated into 3D gradient echo (GRE) and fast spin echo (FSE) protocols on a shielding-free 0.055T head scanner. MT effects were first verified using phantoms. Brain MT imaging was conducted in both healthy subjects and patients. RESULTS: MT effects were clearly observed in phantoms using six SPT modules with total flip angle 3600° at central primary saturation bands of approximate offset ±786 Hz, even in the presence of large relative B0 inhomogeneity. For brain, strong MT effects were observed in gray matter, white matter, and muscle in 3D GRE and FSE imaging using six and sixteen SPT modules with total flip angle 3600° and 9600°, respectively. Fat, cerebrospinal fluid, and blood exhibited relatively weak MT effects. MT preparation enhanced tissue contrasts in T2-weighted and FLAIR-like images, and improved brain lesion delineation. The estimated MT SAR was 0.0024 and 0.0008 W/kg for two protocols, respectively, which is far below the US Food and Drug Administration (FDA) limit of 3.0 W/kg. CONCLUSION: Robust MT effects can be readily obtained at ULF with extremely low SAR, despite poor relative B0 homogeneity in ppm. This unique advantage enables flexible MT pulse design and implementation on low-cost ULF MRI platforms to achieve strong MT effects in brain and beyond, potentially augmenting their clinical utility in the future.

Capabilities of Microbial Consortia from Disparate Environment Matrices in the Decomposition of Nature Organic Matter by Biofiltration.

Dissolved organic matter (DOM) plays a pivotal role in drinking water treatment, influencing the performance of unit processes and final water quality (e.g. disinfection byproduct risk). Biofiltration is an effective method of reducing DOM, but currently lacks a comprehensive appreciation of the association between microbial profiles and biofiltration performance. In this study, bench-scale biofiltration units inoculated with microbial consortia from river and soil matrices were operated successively for comparing their efficacy in terms of DOM removal. The results showed that biofiltration units receiving soil microbes were significantly superior (p < 0.05) to those receiving river inoculated microbes in terms of decomposing DOM recalcitrant fractions and reducing DBP formation potential, resulting in DOC and DBP precursor removals of up to 58.4 % and 87.9 %, respectively. Characterization of the taxonomic composition revealed that differences in the microbial assembly of the two biofilter groups were subject to deterministic rather than stochastic factors. Furthermore, more complicated interspecific relationships and niche structures in soil inoculated biofilters were deciphered by co-occurrence network, providing a plausible profile on a taxonomic division of labor in DOM stepwise degradation. Accordingly, the contribution of microbial compositions was found to be of greater importance than the GAC mass and biomass attached to the media. Thus, this study has advanced the understanding of microbial-mediated DOM decomposition in biofiltration, and also provided a promising strategy for enhancing the process for water use via developing appropriate engineered consortia of bacteria.

Bioinformatics and functional analysis of EDS1 genes in Brassica napus in response to Plasmodiophora brassicae infection.

Enhanced Disease Susceptibility 1 (EDS1) is a key regulator of plant-pathogen-associated molecular pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) responses. In the Brassica napus genome, we identified six novel EDS1 genes, among which four were responsive to clubroot infection, a major rapeseed disease resistant to chemical control. Developing resistant cultivars is a potent and economically viable strategy to control clubroot infection. Bioinformatics analysis revealed conserved domains and structural uniformity in Bna-EDS1 homologs. Bna-EDS1 promoters harbored elements associated with diverse phytohormones and stress responses, highlighting their crucial roles in plant defense. A functional analysis was performed with Bna-EDS1 overexpression and RNAi transgenic lines. Bna-EDS1 overexpression boosted resistance to clubroot and upregulated defense-associated genes (PR1, PR2, ICS1, and CBP60), while Bna-EDS1 RNAi increased plant susceptibility, indicating suppression of the defense signaling pathway downstream of NBS-LRRs. RNA-Seq analysis identified key transcripts associated with clubroot resistance, including phenylpropanoid biosynthesis. Activation of SA regulator NPR1, defense signaling markers PR1 and PR2, and upregulation of MYC-TFs suggested that EDS1-mediated clubroot resistance potentially involves the SA pathway. Our findings underscore the pivotal role of Bna-EDS1-dependent mechanisms in resistance of B. napus to clubroot disease, and provide valuable insights for fortifying resistance against Plasmodiophora brassicae infection in rapeseed.

Exploring the mediating roles of physical literacy and mindfulness on psychological distress and life satisfaction among college students.

Background: Psychological distress has been a growing challenge to healthy living worldwide. Special attention has been concentrated on examining the cost of psychological distress on the life satisfaction of college students who are vulnerable groups coping with the challenge. The purpose of this study is to explore the roles of physical literacy (PL) and mindfulness in mediating the impact of psychological distress on life satisfaction among college students in China. Methods: A sample of 653 students from six universities across three cities in China participated in an online survey, which included measures of PL, mindfulness, life satisfaction, as well as stress, anxiety, and depression levels. Structural equation modeling (SEM) was implemented to analyze the survey data. Results: The findings of the SEM analysis demonstrated an acceptable model fit (X2/df = 3.63, CFI = 0.951, TLI = 0.940, RMSEA = 0.068, 90% CI = [0.060, 0.075], SRMR = 0.051) with a large effect size (R 2 = 0.36) for life satisfaction, indicating that 36% of the variation in life satisfaction could be explained by the model. In addition, significant partial-mediation effects of PL and mindfulness were observed in the relationship between psychological distress and life satisfaction. These findings provide empirical support for the notion that interventions targeting PL and mindfulness practices may effectively enhance well-being and alleviate psychological distress among college students. Furthermore, this study suggests that integrating PL and mindfulness components into physical education and activity programs could be beneficial in meeting individuals' holistic health needs.

Integrated Multi-Omics Analysis to Reveal the Molecular Mechanisms of Inflorescence Elongation in Medicago sativa.

The morphological architecture of inflorescence influences seed production. The regulatory mechanisms underlying alfalfa (Medicago sativa) inflorescence elongation remain unclear. Therefore, in this study, we conducted a comparative analysis of the transcriptome, proteome, and metabolome of two extreme materials at three developmental stages to explore the mechanisms underlying inflorescence elongation in alfalfa. We observed the developmental processes of long and short inflorescences and found that the elongation capacity of alfalfa with long inflorescence was stronger than that of alfalfa with short inflorescences. Furthermore, integrative analysis of the transcriptome and proteome indicated that the phenylpropanoid biosynthesis pathway was closely correlated with the structural formation of the inflorescence. Additionally, we identified key genes and proteins associated with lignin biosynthesis based on the differential expressed genes and proteins (DEGs and DEPs) involved in phenylpropanoid biosynthesis. Moreover, targeted hormone metabolome analysis revealed that IAA, GA, and CK play an important role in the peduncle elongation of alfalfa inflorescences. Based on omics analysis, we detected key genes and proteins related to plant hormone biosynthesis and signal transduction. From the WGCNA and WPCNA results, we furthermore screened 28 candidate genes and six key proteins that were correlated with lignin biosynthesis, plant hormone biosynthesis, and signaling pathways. In addition, 19 crucial transcription factors were discovered using correlation analysis that might play a role in regulating candidate genes. This study provides insight into the molecular mechanism of inflorescence elongation in alfalfa and establishes a theoretical foundation for improving alfalfa seed production.

Asymmetric Dearomatization of Indoles through Cobalt-Catalyzed Enantioselective C-H Functionalization Enabled by Photocatalysis.

Photocatalysis holds a pivotal position in modern organic synthesis, capable of inducing novel reactivities under mild and environmentally friendly reaction conditions. However, the merger of photocatalysis and transition-metal-catalyzed asymmetric C-H activation as an efficient and sustainable method for the construction of chiral molecules remains elusive and challenging. Herein, we develop a cobalt-catalyzed enantioselective C-H activation reaction enabled by visible-light photoredox catalysis, providing a synergistic catalytic strategy for the asymmetric dearomatization of indoles with high levels of enantioselectivity (96 % to >99 % ee). Mechanistic studies indicate that the excited photocatalyst was quenched by divalent cobalt species in the presence of Salox ligand, leading to the formation of catalytically active chiral Co(III) complex. Moreover, stoichiometric reactions of cobaltacycle intermediate with indole suggest that the irradiation of visible light also play a critical role in the dearomatization step.

A cyclic dipeptide for salinity stress alleviation and the trophic flexibility of endophyte provide insights into saltmarsh plant-microbe interactions.

In response to climate change, the nature of endophytes and their applications in sustainable agriculture have attracted the attention of academics and agro-industries. This work focused on the endophytic halophiles of the endangered Taiwanese salt marsh plant, Bolboschoenus planiculmis, and evaluated the functions of these isolates through in planta salinity stress alleviation assay using Arabidopsis. The endophytic strain Priestia megaterium BP01R2, which can promote plant growth and salinity tolerance, was further characterized through multi-omics approaches. The transcriptomics results suggested that BP01R2 could function by tuning hormone signal transduction, energy-producing metabolism, multiple stress responses, etc. In addition, the cyclodipeptide cyclo(L-Ala-Gly), which was identified by metabolomics analysis, was confirmed to contribute to the alleviation of salinity stress in stressed plants via exogenous supplementation. In this study, we used multi-omics approaches to investigate the genomics, metabolomics, and tropisms of endophytes, as well as the transcriptomics of plants in response to the endophyte. The results revealed the potential molecular mechanisms underlying the occurrence of biostimulant-based plant-endophyte symbioses with possible application in sustainable agriculture.

Bmi1 facilitates the progression of cholangiocarcinoma by inhibiting Foxn2 expression dependent on a histone H2A ubiquitination manner.

Cholangiocarcinoma (CCA), an exceptionally aggressive malignancy originating from the epithelium of the bile duct, poses a formidable challenge in cancer research and clinical management. Currently, attention is focused on exploring the oncogenic role and prognostic implications associated with Bmi1 in the context of CCA. In our study, we assessed the correlation of Bmi1 and Foxn2 expression across all types of CCA and evaluated their prognostic significance. Our results demonstrated that Bmi1 exhibits significantly upregulated expression in CCA tissues, while Foxn2 expression shows an inverse pattern. Simultaneously, the high expression of Bmi1, coupled with the low expression of Foxn2, indicates an unfavorable prognosis. Through in vitro and in vivo experiments, we confirmed the crucial role of Foxn2 in the proliferation, metastasis, and epithelial-mesenchymal transition (EMT) of CCA. Mechanistically, Bmi1 promotes the ubiquitination of histone H2A (H2AUb), leading to chromatin opening attenuation and a decrease in Foxn2 expression, ultimately driving CCA progression. Additionally, we described the potential value of Bmi1 and H2AUb inhibitors in treating CCA through in vitro experiments and orthotopic models. This study is of significant importance in deepening our understanding of the interaction between Bmi1 and Foxn2 in CCA and has the potential to advance the development of precision therapies for CCA.

Cobalt-Catalyzed Domino Transformations via Enantioselective C-H Activation/Nucleophilic [3 + 2] Annulation toward Chiral Bridged Bicycles.

Selective synthesis of chiral bridged (hetero)bicyclic scaffolds via asymmetric C-H activation constitutes substantial challenges due to the multiple reactivities of strained bicyclic structures. Herein, we develop the domino transformations through an unprecedented cobalt-catalyzed enantioselective C-H activation/nucleophilic [3 + 2] annulation with symmetrical bicyclic alkenes. The methods offer straightforward access to a wide range of chiral molecules bearing [2.2.1]-bridged bicyclic cores with four and five consecutive stereocenters in a single step. Two elaborate salicyloxazoline (Salox) ligands were synthesized based on the rational design and mechanistic understanding. The well-defined chiral pockets generated from asymmetric coordination around the trivalent cobalt catalyst direct the orientation of bicyclic alkenes, leading to excellent enantioselectivity.

Advances in Polymeric Nanomaterial-mediated Autophagy for Cancer Therapy.

Autophagy is an important biological mechanism for eukaryotic cells to regulate growth, death, and energy metabolism, and plays an important role in removing damaged organelles, misfolded or aggregated proteins, and clearing pathogens. It has been found that autophagy is closely related to cell survival and death, and is of great significance in cancerigenesis and development, playing a bidirectional role in cancer inhibition and cancer promotion. Therefore, treating cancers by regulating autophagy has attracted much attention. A large amount of research evidence indicates that polymeric nanomaterials are able to regulate cellular autophagy, and their good biocompatibility, degradability, and functionalizable modification open up a broad application prospect for improving the therapeutic effect of cancers. This review provides an overview of the research progress of polymeric nanomaterials for modulating autophagy in the treatment of cancers.

Investigation of subclinical ocular inflammation in the aqueous humor of patients with myopia following bilateral sequential collamer lens implantation.

BACKGROUND: The aqueous humor, a transparent fluid secreted by the ciliary body, supports the lens of the eyeball. In this study, we analyzed the cytokine and chemokine profiles within the aqueous humor of the contralateral eye post-implantation of an implantable collamer lens (ICL) to evaluate potential subclinical inflammation in the second eye subsequent to ICL implantation in the first eye. METHODS: Aqueous humor samples were procured from both eyes of 40 patients (totaling 80 eyes) prior to bilateral ICL insertion. Subsequently, a comprehensive statistical analysis was conducted using the Luminex assay to quantify 30 different cytokines in these samples. RESULTS: Compared to the first eye, the aqueous humor of the second eye demonstrated decreased concentrations of IFN-γ (P = 0.038), IL-13 (P = 0.027), IL-17/IL-17 A (P = 0.012), and IL-4 (P = 0.025). No significant differences were observed in other cytokine levels between the two groups. Patients were then categorized based on the postoperative rise in intraocular pressure (IOP) in the first eye. The group with elevated IOP displayed elevated levels of EGF in the aqueous humor of the first eye (P = 0.013) and higher levels of PDGF-AB/BB in the aqueous humor of the second eye (P = 0.032) compared to the group with normal IOP. Within the elevated IOP group, the levels of EGF (P = 0.013) and IL-17/IL-17 A (P = 0.016) in the aqueous humor were lower in the second eye than in the first eye. In the normal IOP group, cytokine levels did not differ notably between eyes. CONCLUSION: Following sequential ICL implantation, it appears that a protective response may be activated to mitigate subclinical inflammation in the second eye induced by the initial implantation in the first eye. Additionally, the increase in IOP subsequent to surgery in the first eye may correlate with the presence of inflammatory mediators in the aqueous humor.

MnO2-based capacitive system enhances ozone inactivation of bacteria by disrupting cell membrane.

The application of ozone (O3) disinfection has been hindered by its low solubility in water and the formation of disinfection by-products (DBPs). In this study, capacitive disinfection is applied as a pre-treatment for O3 oxidation, in which manganese dioxide with a rambutan-like hollow spherical structure is used as the electrode to increase the charge density on the electrode surface. When a voltage is applied, the negative-charged microbes are attracted to the electrodes and killed by electrical interactions. The contact between microbes and capacitive electrodes leads to changes in cell permeability and burst of reactive oxygen species, thereby promoting the diffusion of O3 into the cells. After O3 penetrates the cell membrane, it can directly attack the cytoplasmic constituents, accelerating fatal and irreversible damage to pathogens. As a result, the performance of the capacitance-O3 process is proved better than the direct sum of the two individual process efficiencies. The design of capacitance-O3 system is beneficial to reduce the ozone dosage and DBPs with a broader inactivation spectrum, which is conducive to the application of ozone in primary water disinfection.