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Many spatially resolved transcriptomic technologies do not have single-cell resolution but measure the average gene expression for each spot from a mixture of cells of potentially heterogeneous cell types. Here, we introduce a deconvolution method, conditional autoregressive-based deconvolution (CARD), that combines cell-type-specific expression information from single-cell RNA sequencing (scRNA-seq) with correlation in cell-type composition across tissue locations. Modeling spatial correlation allows us to borrow the cell-type composition information across locations, improving accuracy of deconvolution even with a mismatched scRNA-seq reference. CARD can also impute cell-type compositions and gene expression levels at unmeasured tissue locations to enable the construction of a refined spatial tissue map with a resolution arbitrarily higher than that measured in the original study and can perform deconvolution without an scRNA-seq reference. Applications to four datasets, including a pancreatic cancer dataset, identified multiple cell types and molecular markers with distinct spatial localization that define the progression, heterogeneity and compartmentalization of pancreatic cancer. Analysis of spatial transcriptomics is improved by correlating cell-type compositions across tissue locations.

Drought and salinity are among the most important environmental factors that hampered agricultural productivity worldwide. Both stresses can induce several morphological, physiological, biochemical, and metabolic alterations through various mechanisms, eventually influencing plant growth, development, and productivity. The responses of plants to these stress conditions are highly complex and depend on other factors, such as the species and genotype, plant age and size, the rate of progression as well as the intensity and duration of the stresses. These factors have a strong effect on plant response and define whether mitigation processes related to acclimation will occur or not. In this review, we summarize how drought and salinity extensively affect plant growth in agriculture ecosystems. In particular, we focus on the morphological, physiological, biochemical, and metabolic responses of plants to these stresses. Moreover, we discuss mechanisms underlying plant-microbe interactions that confer abiotic stress tolerance.

Excitotoxicity is one of the primary mechanisms of cell loss in a variety of diseases of the central and peripheral nervous systems. Other than the previously established signaling pathways of excitotoxicity, which depend on the excessive release of glutamate from axon terminals or over-activation of NMDA receptors (NMDARs), Ca 2+ influx-triggered excitotoxicity through Ca 2+ -permeable (CP)-AMPA receptors (AMPARs) is detected in multiple disease models. In this review, both acute brain insults (e.g., brain trauma or spinal cord injury, ischemia) and chronic neurological disorders, including Epilepsy/Seizures, Huntington’s disease (HD), Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), chronic pain, and glaucoma, are discussed regarding the CP-AMPAR-mediated excitotoxicity. Considering the low expression or absence of CP-AMPARs in most cells, specific manipulation of the CP-AMPARs might be a more plausible strategy to delay the onset and progression of pathological alterations with fewer side effects than blocking NMDARs.

Background Dimensionality reduction is an indispensable analytic component for many areas of single-cell RNA sequencing (scRNA-seq) data analysis. Proper dimensionality reduction can allow for effective noise removal and facilitate many downstream analyses that include cell clustering and lineage reconstruction. Unfortunately, despite the critical importance of dimensionality reduction in scRNA-seq analysis and the vast number of dimensionality reduction methods developed for scRNA-seq studies, few comprehensive comparison studies have been performed to evaluate the effectiveness of different dimensionality reduction methods in scRNA-seq. Results We aim to fill this critical knowledge gap by providing a comparative evaluation of a variety of commonly used dimensionality reduction methods for scRNA-seq studies. Specifically, we compare 18 different dimensionality reduction methods on 30 publicly available scRNA-seq datasets that cover a range of sequencing techniques and sample sizes. We evaluate the performance of different dimensionality reduction methods for neighborhood preserving in terms of their ability to recover features of the original expression matrix, and for cell clustering and lineage reconstruction in terms of their accuracy and robustness. We also evaluate the computational scalability of different dimensionality reduction methods by recording their computational cost. Conclusions Based on the comprehensive evaluation results, we provide important guidelines for choosing dimensionality reduction methods for scRNA-seq data analysis. We also provide all analysis scripts used in the present study at www.xzlab.org/reproduce.html .

Permeability is a critical parameter for evaluating the production potential of natural gas hydrate reservoirs, and its accurate prediction is essential for enhanced oil recovery (EOR). However, existing permeability models often assume a uniform particle distribution, neglecting the inherent heterogeneity of natural sediments, and rarely fully couple the effects of effective stress and temperature variations induced by EOR operations. To address that gap, this study develops a novel non-empirical fractal permeability model that incorporates particle heterogeneity through an offset angle (θ) and an aspect ratio (m), and couples these with thermoelastic theory to describe the evolution of the pore structure under coupled thermo-mechanical conditions. The model accounts for two hydrate growth habits (grain-coating and pore-filling) and allows for their coexistence via weighting coefficients. Using this model, we systematically investigate the individual and combined effects of effective stress, temperature, particle heterogeneity, and hydrate saturation on permeability. Model predictions are validated against independent experimental data from multiple sources, showing good agreement. The results reveal that permeability decreases with increasing effective stress and temperature, with stress playing a more dominant role; moreover, the transition between hydrate growth habits under stress is captured. The proposed model provides a theoretical tool to understand permeability evolution in heterogeneous hydrate reservoirs under varying thermo-mechanical conditions, thereby supporting EOR strategy optimization.

This study examined the antibacterial effect of protoporphyrin IX-ethylenediamine derivative (PPIX-ED)-mediated photodynamic antimicrobial chemotherapy (PPIX-ED-PACT) against Pseudomonas aeruginosa in vitro and in vivo. PPIX-ED potently inhibited the growth of Pseudomonas aeruginosa by inducing reactive oxygen species production via photoactivation. Atomic force microscopy revealed that PPIX-ED-PACT induced the leakage of bacterial content by degrading the bacterial membrane and wall. As revealed using acridine orange/ethidium bromide staining, PPIX-ED-PACT altered the permeability of the bacterial membrane. In addition, the antibacterial effect of PPIX-ED-PACT was demonstrated in an in vivo model of P. aeruginosa-infected wounds. PPIX-ED (100 [mu]M) decreased the number of P. aeruginosa colony-forming units by 4.2 log.sub.10 . Moreover, histological analysis illustrated that the wound healing rate was 98% on day 14 after treatment, which was 10% higher than that in the control group. According to the present findings, PPIX-ED-PACT can effectively inhibit the growth of P. aeruginosa in vitro and in vivo.

Global climate change-induced abiotic stresses (e.g., drought, salinity, extreme temperatures, heavy metals, and UV radiation) have destabilized the fragile agroecosystems and impaired plant performance and thereby reducing crop productivity and quality. Biostimulants, as a promising and eco-friendly approach, are widely used to address environmental concerns and fulfill the need for developing sustainable/modern agriculture. Current knowledge revealed that plant and animal derived stimulants (e.g., seaweeds and phytoextracts, humic substances, and protein hydrolysate) as well as microbial stimulants (e.g., plant beneficial bacteria or fungi) have great potential to elicit plant tolerance to various abiotic stresses and thus enhancing plant growth and performance-related parameters (such as root growth/diameter, flowering, nutrient use efficiency/translocation, soil water holding capacity, and microbial activity). However, to successfully implement biostimulant-based agriculture in the field under changing climate, the understanding of agricultural functions and action mechanism of biostimulants coping with various abiotic stresses at physicochemical, metabolic, and molecular levels is needed. Therefore, this review attempts to unravel the underlying mechanisms of action mediated by diverse biostimulants in relation to abiotic stress alleviation as well as to discuss the current challenges in their commercialization and implementation in agriculture under changing climate conditions.

Background Chronic diseases have a high incidence in China and may cause pain and depression. However, the association of chronic diseases with pain and the incidence of depression has not been comprehensively investigated. Methods The study population was obtained from the 2015 China Health and Retirement Longitudinal Study (CHARLS). The cross-sectional data from15,213 persons were included. CHARLS provides nationally representative data from21,097 individuals aged 45 years and older in approximately 150 districts and 450 villages. The main outcome was the incidence of depression. The main independent variable was chronic disease (no chronic disease, one chronic disease, and two or more chronic diseases). The mediators were the degree of pain (no pain, mild pain, and moderate to severe pain) and whether measures were taken to relieve pain (measures taken and no measures taken). We performed chi-square and binary logistic regression analyses of the associations of chronic disease with pain and the incidence of depression. The mediation model was examined using the Sobel test. Results Patients with more chronic diseases had more severe pain (OR = 3.697, P  < 0.001, CI = 2.919–4.681) and were more likely to develop depression (OR = 2.777, P < 0.001, CI = 2.497–3.090). The degree of pain partially mediated the interaction between chronic disease and depression in this study (t = 7.989, P  < 0.001). The incidence of depression was high in people who were female, less educated, unmarried, living in rural areas, and working. Conclusions The degree of pain had a partial mediating effect on chronic disease and depression. Pain relief measures should be considered when treating patients with depression.

Non-small cell lung cancer (NSCLC) is a common type of lung cancer, characterized by a poor prognosis. In the last several years, more and more studies have demonstrated the significant roles played by circular RNAs (circRNAs) in different human tumors progression including NSCLC. The present study was to explore the mechanism of hsa_circ_101237 in regulating non-small cell lung cancer (NSCLC). Totally 303 NSCLC cases were enrolled. A549 and H1299 cells were transfected. Cells viability, migration and invasion were determined by CCK-8 assay and transwell experiment, respectively. Luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay were performed. hsa_circ_101237, miR-490-3p and MAPK1 expression in tissues/cells were detected by qRT-PCR. The study found an elevation in the expression of Hsa_circRNA_101237 in both NSCLC tissues and cell line. High Hsa_circRNA_101237 expression predicted poor survival in NSCLC. Meanwhile, we found that hsa_circRNA_101237 expression sponged miR-490-3p to enhance MAPK1 expression, thus significantly promoting NSCLC cell lines proliferation, migration, and invasion. MAPK1 restoration prevented NSCLC cells proliferation, migration, and invasion to be repressed due to hsa_circRNA_101237 knockdown. To sum up, as revealed by the study, hsa_circRNA_101237 promoted the expression of MAPK1 via miRNA-490-3p sponge, thus affecting the NSCLC as an important onco-circRNA.