Multi-modal domain adaptation for revealing spatial functional landscape from spatially resolved transcriptomics.

Spatially resolved transcriptomics (SRT) has emerged as a powerful tool for investigating gene expression in spatial contexts, providing insights into the molecular mechanisms underlying organ development and disease pathology. However, the expression sparsity poses a computational challenge to integrate other modalities (e.g. histological images and spatial locations) that are simultaneously captured in SRT datasets for spatial clustering and variation analyses. In this study, to meet such a challenge, we propose multi-modal domain adaption for spatial transcriptomics (stMDA), a novel multi-modal unsupervised domain adaptation method, which integrates gene expression and other modalities to reveal the spatial functional landscape. Specifically, stMDA first learns the modality-specific representations from spatial multi-modal data using multiple neural network architectures and then aligns the spatial distributions across modal representations to integrate these multi-modal representations, thus facilitating the integration of global and spatially local information and improving the consistency of clustering assignments. Our results demonstrate that stMDA outperforms existing methods in identifying spatial domains across diverse platforms and species. Furthermore, stMDA excels in identifying spatially variable genes with high prognostic potential in cancer tissues. In conclusion, stMDA as a new tool of multi-modal data integration provides a powerful and flexible framework for analyzing SRT datasets, thereby advancing our understanding of intricate biological systems.

Spatially contrastive variational autoencoder for deciphering tissue heterogeneity from spatially resolved transcriptomics.

Recent advances in spatially resolved transcriptomics (SRT) have brought ever-increasing opportunities to characterize expression landscape in the context of tissue spatiality. Nevertheless, there still exist multiple challenges to accurately detect spatial functional regions in tissue. Here, we present a novel contrastive learning framework, SPAtially Contrastive variational AutoEncoder (SpaCAE), which contrasts transcriptomic signals of each spot and its spatial neighbors to achieve fine-grained tissue structures detection. By employing a graph embedding variational autoencoder and incorporating a deep contrastive strategy, SpaCAE achieves a balance between spatial local information and global information of expression, enabling effective learning of representations with spatial constraints. Particularly, SpaCAE provides a graph deconvolutional decoder to address the smoothing effect of local spatial structure on expression's self-supervised learning, an aspect often overlooked by current graph neural networks. We demonstrated that SpaCAE could achieve effective performance on SRT data generated from multiple technologies for spatial domains identification and data denoising, making it a remarkable tool to obtain novel insights from SRT studies.

Multi-point immobilization of GH 11 endo-ß-1,4-xylanase on magnetic MOF composites for higher yield of xylo-oligosaccharides.

GH 11 endo-ß-1,4-xylanase (Xy) was a crucial enzyme for xylooligosaccharides (XOS) production. The lower reusability and higher cost of purification has limited the industrial application of Xy. Addressing these challenges, our study utilized various immobilization techniques, different supports and forces for Xy immobilization. This study presents a new method in the development of Fe3O4@PDA@MOF-Xy which is immobilized via multi-point interaction forces, demonstrating a significant advancement in protein loading capacity (80.67 mg/g), and exhibiting remarkable tolerance to acidic and alkaline conditions. This method significantly improved Xy reusability and efficiency for industrial applications, maintaining 60 % activity over 10 cycles. Approximately 23 % XOS production was achieved by Fe3O4@PDA@MOF-Xy. Moreover, the yield of XOS from cobcorn xylan using this system was 1.15 times higher than that of the free enzyme system. These results provide a theoretical and applicative basis for enzyme immobilization and XOS industrial production.

Global, regional and national burden of ischemic stroke attributed to high low-density lipoprotein cholesterol, 1990-2019：A decomposition analysis and age-period-cohort analysis.

High levels of low-density lipoprotein cholesterol (LDL-C) have been associated with an augmented mortality of ischemic stroke. The yearly deaths and mortality data of IS-hLDL-C were derived from the global burden of disease 2019 dataset. The joinpoint, age-period-cohort and decomposition analysis were utilized to evaluate the long-term patterns in the disease burden of IS-hLDL-C, and the effects of population growth and aging. Globally, in 2019, 0.61 million ischemic stroke-related deaths were attributable to high LDL-C, with the highest death burden in the high-middle socio-demographic index (SDI) region. From 1990 to 2019, the age-standardized death rate (ASDR) for IS-hLDL-C exhibited a downward trend, with an average annual percentage change of -1.69 [95% confidence interval: -1.90, -1.48)]. The fastest decreasing trends in ASDR were experienced in the high SDI region. In 119 (58.33%) countries, aging increased the disease burden of hLDL-IS, and population growth increased the disease burden of IS-hLDL-C in 163 (79.90%) countries. The trend in disease burden of IS-hLDL-C exhibited variation across countries and regions, particularly in territories with high to middle high SDI. Aging in upper to middle-income countries and population growth in low to middle-income countries further offset endeavors to reduce the burden of ischemic stroke deaths.

To PCR or not? The impact of shifting policy from PCR to rapid antigen tests to diagnose COVID-19 during the omicron epidemic: a nationwide surveillance study.

Background: Coronavirus disease 2019 (COVID-19) had caused huge impacts worldwide. Polymerase chain reaction (PCR) is the mainstay diagnostic modality. In most hospitals in Taiwan, samples for PCR are collected at emergency department (ER) or outdoor clinics to avoid virus spread inside hospitals. Home rapid antigen test (RAT) is a feasible, low-cost, and convenient tool with moderate sensitivity and high specificity, which can be performed at home to reduce hospital visits. Due to comparably low severity of omicron variant and high vaccine coverage (~80% residents fully vaccinated with AstraZeneca, Moderna, or Pfizer BioNTech COVID-19 vaccines as of March 2022), the policy was shifted from containment to co-existing with COVID-19 in Taiwan. Virus spread rapidly in the community after the ease of social restrictive measurements. To acquire a confirmed diagnosis, PCR testing was requested for people with suspected COVID-19 infection. As a consequence, people with respiratory symptoms or contact history surged into hospitals for PCR testing, thus, the medical capacity was challenged. The diagnostic policy was altered from PCR to RAT, but the impact of diagnostic policy change remains unclear. Objectives: We conducted this study to investigate the number of COVID-19 cases, PCR testing, hospitalizations, mortalities, and hospital visits during the epidemic and evaluate the impact of diagnostic policy change on hospital visits. Methods: The diagnostic policy change was implemented in late May 2022. We used nationwide and hospital-based data of COVID-19 cases, PCR testing, hospitalizations, mortalities, and hospital visits before and after policy change as of 31 Jul 2022. Results: During the omicron epidemic, significant and synchronous increase of COVID-19 patients, PCR testing, hospital visits were observed. COVID-19 cases increased exponentially since April 2022 and the COVID-19 patients peaked in June (1,943, 55,571, and 61,511 average daily new cases in April, May, and June, respectively). The PCR testing peaked in May (85,788 daily tests) with high positive rate (81%). The policy of RAT as confirmatory diagnosis was implemented on 26 May 2022 and a substantial decline of PCR testing numbers occurred (85,788 and 83,113 daily tests in May and June). People hospitalized for COVID-19 peaked in June (821.8 patients per day) and decreased in July (549.5 patients). The mortality cases also peaked in June (147 cases/day). This trend was also validated by the hospital-based data with a significant decrease of emergency department visits (11,397 visits in May while 8,126 visits in June) and PCR testing (21,314 in May and 6,158 in June). The proportion of people purely for PCR testing also decreased (10-26 vs. 5-14%, before and after policy change, respectively). Conclusions: The impact of diagnostic policy change was a complicated issue and our study demonstrated the huge impact of diagnostic policy on health seeking behavior. The PCR testing numbers and emergency department visits had substantial decrease after diagnostic policy change, and the plateau of epidemic peak eased gradually in ~1 month later. Widespread RAT application may contribute to the decreased hospital visits and preserve medical capacity. Our study provides some evidences for policy maker's reference.

The trend of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in spontaneous intracerebral hemorrhage and the predictive value of short-term postoperative prognosis in patients.

Background: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) play an important role in the inflammatory response in various diseases, but the role in the course of spontaneous intracerebral hemorrhage (ICH) is unclear. Methods: This study retrospectively collected baseline characteristics and laboratory findings, including NLR and PLR at different time points, from spontaneous ICH patients undergoing surgery between January 2016 and June 2021. Patients were scored using the modified Rankin Scale (mRS) to evaluate their functional status at 30 days post-operation. Patients with mRS score ≥3 were defined as poor functional status, and mRS score <3 was defined as good functional status. The NLR and PLR were calculated at admission, 48 h after surgery and 3-7 days after surgery, respectively, and their trends were observed by connecting the NLR and PLR at different time points. Multivariate logistic regression analysis was used to identify independent risk factors affecting the prognosis of ICH patients at 30 days after surgery. Results: A total of 101 patients were included in this study, and 59 patients had a poor outcome at 30 days after surgery. NLR and PLR gradually increased and then decreased, peaking at 48 h after surgery. Univariate analysis demonstrated that admission Glasgow Coma Scale (GCS) score, interval from onset to admission, hematoma location, NLR within 48 h after surgery and PLR within 48 h after surgery were associated with poor 30-day prognosis. In multivariate logistic regression analysis, NLR within 48 h after surgery (OR, 1.147; 95% CI, 1.005, 1.308; P, 0.042) was an independent risk factor for 30-day after surgery prognosis in spontaneous ICH patients. Conclusion: In the course of spontaneous intracerebral hemorrhage, NLR and PLR initially increased and subsequently decreased, reaching their peak values at 48 h after surgery. High NLR within 48 h after surgery was an independent risk factor for poor prognosis 30 days after surgery in spontaneous ICH patients.

MYCL promotes the progression of triple­negative breast cancer by activating the JAK/STAT3 pathway.

The present study aimed to investigate the underlying regulatory mechanism of MYCL proto­oncogene (MYCL) in triple­negative breast cancer (TNBC) progression. In vitro experiments were performed to confirm the functional roles of MYCL in TNBC, and its effects on the JAK/STAT3 pathway through flow cytometric analysis, colony formation, wound healing and Transwell assays. In addition, the GSE45498 dataset demonstrated that MYCL was upregulated in TNBC and that it was significantly related to poor survival of patients with TNBC. Knockdown of MYCL induced the apoptosis, and suppressed the proliferation, migration and invasion of TNBC cells by inhibiting the JAK/STAT3 pathway. Notably, MYCL could activate the JAK/STAT3 pathway, whereas inhibition of the JAK/STAT3 pathway could eliminate the effect of MYCL on TNBC cells. Knockdown of MYCL also suppressed the growth of TNBC xenograft tumors. In conclusion, MYCL could promote TNBC progression by activating the JAK/STAT3 pathway.

Identification of Hub Gene GRIN1 Correlated with Histological Grade and Prognosis of Glioma by Weighted Gene Coexpression Network Analysis.

The function of glutamate ionotropic receptor NMDA type subunit 1 (GRIN1) in neurodegenerative diseases has been widely reported; however, its role in the occurrence of glioma remains less explored. We obtained clinical data and transcriptome data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Hub gene's expression differential analysis and survival analysis were conducted by browsing the Gene Expression Profiling Interactive Analysis (GEPIA) database, Human Protein Atlas database, and LOGpc database. We conducted a variation analysis of datasets obtained from GEO and TCGA and performed a weighted gene coexpression network analysis (WGCNA) using the R programming language (3.6.3). Kaplan-Meier (KM) analysis was used to calculate the prognostic value of GRIN1. Finally, we conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Using STRING, we constructed a protein-protein interaction (PPI) network. Cytoscape software, a prerequisite of visualizing core genes, was installed, and CytoHubba detected the 10 most tumor-related core genes. We identified 185 differentially expressed genes (DEGs). GO and KEGG enrichment analyses illustrated that the identified DEGs are imperative in different biological functions and ascertained the potential pathways in which the DEGs may be enriched. The overall survival calculated by KM analysis showed that patients with lower expression of GRIN1 had worse prognoses than patients with higher expression of GRIN1 (p = 0.004). The GEPIA and LOGpc databases were used to verify the expression difference of GRIN1 among GBM, LGG, and normal brain tissues. Ultimately, immunohistochemical assay results showed that GRIN1 was detected in normal tissue and not in the tumor specimens. Our results highlight a potential target for glioma treatment and will further our understanding of the molecular mechanisms underlying the treatment of glioma.

Dynamics of Pickering Emulsions in the Presence of an Interfacial Reaction: A Simulation Study.

Pickering emulsions combining surface-active and catalytic properties offer a promising platform for conducting interfacial reactions between immiscible reagents. Despite the significant progress in the design of Pickering interfacial catalysts for a broad panel of reactions, the dynamics of Pickering emulsions under reaction conditions is still poorly understood. Herein, using benzene hydroxylation with aqueous H2O2 as a model system, we explored the dynamics of benzene/water Pickering emulsions during reaction by dissipative particle dynamics. Our study points out that the surface wettability of the silica nanoparticles is affected to a higher extent by the degree of polymer grafting rather than an increase of the chain length of hydrophobic polymer moieties. A remarkable decline of the oil-in-water (O/W) interfacial tension was observed when increasing the yield of the reaction product (phenol), affecting the emulsion stability. However, phenol did not alter to an important extent the distribution of immiscible reagents around the nanoparticles sitting at the benzene/water interface. A synergistic effect between phenol and silica nanoparticles on the O/W interfacial tension of the biphasic system could be ascertained.