Microfluidic Biochips for Single-Cell Isolation and Single-Cell Analysis of Multiomics and Exosomes.

Single-cell multiomic and exosome analyses are potent tools in various fields, such as cancer research, immunology, neuroscience, microbiology, and drug development. They facilitate the in-depth exploration of biological systems, providing insights into disease mechanisms and aiding in treatment. Single-cell isolation, which is crucial for single-cell analysis, ensures reliable cell isolation and quality control for further downstream analyses. Microfluidic chips are small lightweight systems that facilitate efficient and high-throughput single-cell isolation and real-time single-cell analysis on- or off-chip. Therefore, most current single-cell isolation and analysis technologies are based on the single-cell microfluidic technology. This review offers comprehensive guidance to researchers across different fields on the selection of appropriate microfluidic chip technologies for single-cell isolation and analysis. This review describes the design principles, separation mechanisms, chip characteristics, and cellular effects of various microfluidic chips available for single-cell isolation. Moreover, this review highlights the implications of using this technology for subsequent analyses, including single-cell multiomic and exosome analyses. Finally, the current challenges and future prospects of microfluidic chip technology are outlined for multiplex single-cell isolation and multiomic and exosome analyses.

Pseudospin-dependent acoustic topological edge and corner states in silica aerogel metamaterialsa).

Fueled by the concepts of topological insulators, analogous topological acoustics offer an alternative approach to manipulate sound. Theoretical proposals for subwavelength acoustic topological insulators are considered to be ideal effective parameters or utilizeing artificial coiling-space metamaterials. However, the corresponding realization using realistic soft metamaterials remains challenging. In this study, we present the design of an acoustic subwavelength second-order topological insulator using nanoscale porous solid material, silica aerogel, which supports pseudospin-dependent topological edge and corner states simultaneously. Through simulations and experiments, we demonstrate that silica aerogel can function as a soft acoustic metamaterial at the subwavelength scale. By embedding silica aerogel in an air matrix to construct a honeycomb lattice, a double Dirac cone is obtained. A topological phase transition is induced by expanding or contracting the supercell, resulting in band inversion. Additionally, we propose topologically robust acoustic transmission along the one-dimensional edge. Furthermore, we discover that the proposed sonic crystal sustains zero-dimensional corner states, which can efficiently confine energy at subwavelength corners. These findings offer potential for the realization of subwavelength topological acoustic devices using realistic soft metamaterials.

Aberrant individual structure covariance network in patients with mesial temporal lobe epilepsy.

Objective: Mesial temporal lobe epilepsy (mTLE) is a complex neurological disorder that has been recognized as a widespread global network disorder. The group-level structural covariance network (SCN) could reveal the structural connectivity disruption of the mTLE but could not reflect the heterogeneity at the individual level. Methods: This study adopted a recently proposed individual structural covariance network (IDSCN) method to clarify the alternated structural covariance connection mode in mTLE and to associate IDSCN features with the clinical manifestations and regional brain atrophy. Results: We found significant IDSCN abnormalities in the ipsilesional hippocampus, ipsilesional precentral gyrus, bilateral caudate, and putamen in mTLE patients than in healthy controls. Moreover, the IDSCNs of these areas were positively correlated with the gray matter atrophy rate. Finally, we identified several connectivities with weak associations with disease duration, frequency, and surgery outcome. Significance: Our research highlights the role of hippo-thalamic-basal-cortical circuits in the pathophysiologic process of disrupted whole-brain morphological covariance networks in mTLE, and builds a bridge between brain-wide covariance network changes and regional brain atrophy.

Low energy-consumption oriented membrane fouling control strategy in anaerobic fluidized membrane bioreactor.

Anaerobic fluidized membrane bioreactors (AFMBR) has attracted growing interest as an emerging wastewater treatment technology towards energy recovery from wastewater. AFMBR combines the advantages of anaerobic digestion and membrane bioreactors and shows great potential in overcoming limiting factors such as membrane fouling and low efficiency in treating low-strength wastewater such as domestic sewage. In AFMBR, the fluidized media performs significant role in reducing the membrane fouling, as well as improving the anaerobic microbial activity of AFMBRs. Despite extensive research aimed at mitigating membrane fouling in AFMBR, there has yet to emerge a comprehensive review focusing on strategies for controlling membrane fouling with an emphasis on low energy consumption. Thus, this work overviews the recent progress of AFMBR by summarizing the factors of membrane fouling and energy consumption in AFMBR, and provides targeted in-depth analysis of energy consumption related to membrane fouling control. Additionally, future development directions for AFMBR are also outlooked, and further promotion of AFMBR engineering application is expected. By shedding light on the relationship between energy consumption and membrane fouling control, this review offers a useful information for developing new AFMBR processes with an improved efficiency, low membrane fouling and low energy consumption, and encourages more research efforts and technological advancements in the domain of AFMBR.

Antarctic Snow Failure Mechanics: Analysis, Simulations, and Applications.

Snow failure is the process by which the stability of snow or snow-covered slopes is destroyed, resulting in the collapse or release of snow. Heavy snowfall, low temperatures, and volatile weather typically cause consequences in Antarctica, which can occur at different scales, from small, localized collapses to massive avalanches, and result in significant risk to human activities and infrastructures. Understanding snow damage is critical to assessing potential hazards associated with snow-covered terrain and implementing effective risk mitigation strategies. This review discusses the theoretical models and numerical simulation methods commonly used in Antarctic snow failure research. We focus on the various theoretical models proposed in the literature, including the fiber bundle model (FBM), discrete element model (DEM), cellular automata (CA) model, and continuous cavity-expansion penetration (CCEP) model. In addition, we overview some methods to acquire the three-dimensional solid models and the related advantages and disadvantages. Then, we discuss some critical numerical techniques used to simulate the snow failure process, such as the finite element method (FEM) and three-dimensional (3D) material point method (MPM), highlighting their features in capturing the complex behavior of snow failure. Eventually, different case studies and the experimental validation of these models and simulation methods in the context of Antarctic snow failure are presented, as well as the application of snow failure research to facility construction. This review provides a comprehensive analysis of snow properties, essential numerical simulation methods, and related applications to enhance our understanding of Antarctic snow failure, which offer valuable resources for designing and managing potential infrastructure in Antarctica.

EF-Net: Mental State Recognition by Analyzing Multimodal EEG-fNIRS via CNN.

Analysis of brain signals is essential to the study of mental states and various neurological conditions. The two most prevalent noninvasive signals for measuring brain activities are electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS). EEG, characterized by its higher sampling frequency, captures more temporal features, while fNIRS, with a greater number of channels, provides richer spatial information. Although a few previous studies have explored the use of multimodal deep-learning models to analyze brain activity for both EEG and fNIRS, subject-independent training-testing split analysis remains underexplored. The results of the subject-independent setting directly show the model's ability on unseen subjects, which is crucial for real-world applications. In this paper, we introduce EF-Net, a new CNN-based multimodal deep-learning model. We evaluate EF-Net on an EEG-fNIRS word generation (WG) dataset on the mental state recognition task, primarily focusing on the subject-independent setting. For completeness, we report results in the subject-dependent and subject-semidependent settings as well. We compare our model with five baseline approaches, including three traditional machine learning methods and two deep learning methods. EF-Net demonstrates superior performance in both accuracy and F1 score, surpassing these baselines. Our model achieves F1 scores of 99.36%, 98.31%, and 65.05% in the subject-dependent, subject-semidependent, and subject-independent settings, respectively, surpassing the best baseline F1 scores by 1.83%, 4.34%, and 2.13% These results highlight EF-Net's capability to effectively learn and interpret mental states and brain activity across different and unseen subjects.

Insight into key interactions between diverse factors and membrane fouling mitigation in anaerobic membrane bioreactor.

Anaerobic membrane bioreactors (AnMBRs) have garnered considerable attention as a low-energy and low-carbon footprint treatment technology. With an increasing number of scholars focusing on AnMBR research, its outstanding performance in the field of water treatment has gradually become evident. However, the primary obstacle to the widespread application of AnMBR technology lies in membrane fouling, which leads to reduced membrane flux and increased energy demand. To ensure the efficient and long-term operation of AnMBRs, effective control of membrane fouling is imperative. Nevertheless, the interactions between various fouling factors are complex, making it challenging to predict the changes in membrane fouling. Therefore, a comprehensive analysis of the fouling factors in AnMBRs is necessary to establish a theoretical basis for subsequent membrane fouling control in AnMBR applications. This review aims to provide a thorough analysis of membrane fouling issues in AnMBR applications, particularly focusing on fouling factors and fouling control. By delving into the mechanisms behind membrane fouling in AnMBRs, this review offers valuable insights into mitigating membrane fouling, thus enhancing the lifespan of membrane components in AnMBRs and identifying potential directions for future AnMBR research.

The Interplay Between Epilepsy and Parkinson's Disease: Gene Expression Profiling and Functional Analysis.

The results of many epidemiological studies suggest a bidirectional causality may exist between epilepsy and Parkinson's disease (PD). However, the underlying molecular landscape linking these two diseases remains largely unknown. This study aimed to explore this possible bidirectional causality by identifying differentially expressed genes (DEGs) in each disease as well as their intersection based on two respective disease-related datasets. We performed enrichment analyses and explored immune cell infiltration based on an intersection of the DEGs. Identifying a protein-protein interaction (PPI) network between epilepsy and PD, and this network was visualised using Cytoscape software to screen key modules and hub genes. Finally, exploring the diagnostic values of the identified hub genes. NetworkAnalyst 3.0 and Cytoscape software were also used to construct and visualise the transcription factor-micro-RNA regulatory and co-regulatory networks, the gene-microRNA interaction network, as well as gene-disease association. Based on the enrichment results, the intersection of the DEGs mainly revealed enrichment in immunity-, phosphorylation-, metabolism-, and inflammation-related pathways. The boxplots revealed similar trends in infiltration of many immune cells in epilepsy and Parkinson's disease, with greater infiltration in patients than in controls. A complex PPI network comprising 186 nodes and 512 edges were constructed. According to node connection degree, top 15 hub genes were considered the kernel targets of epilepsy and PD. The area under curve values of hub gene expression profiles confirmed their excellent diagnostic values. This study is the first to analyse the molecular landscape underlying the epidemiological link between epilepsy and Parkinson's disease. The two diseases are closely linked through immunity-, inflammation-, and metabolism-related pathways. This information was of great help in understanding the pathogenesis, diagnosis, and treatment of the diseases. The present results may provide guidance for further in-depth analysis about molecular mechanisms of epilepsy and PD and novel potential targets.

Stereo Visual Servoing Control of a Soft Endoscope for Upper Gastrointestinal Endoscopic Submucosal Dissection.

Quickly and accurately completing endoscopic submucosal dissection (ESD) operations within narrow lumens is currently challenging because of the environment's high flexibility, invisible collision, and natural tissue motion. This paper proposes a novel stereo visual servoing control for a dual-segment robotic endoscope (DSRE) for ESD surgery. Departing from conventional monocular-based methods, our DSRE leverages stereoscopic imaging to rapidly extract precise depth data, enabling quicker controller convergence and enhanced surgical accuracy. The system's dual-segment configuration enables agile maneuverability around lesions, while its compliant structure ensures adaptability within the surgical environment. The implemented stereo visual servo controller uses image features for real-time feedback and dynamically updates gain coefficients, facilitating rapid convergence to the target. In visual servoing experiments, the controller demonstrated strong performance across various tasks. Even when subjected to unknown external forces, the controller maintained robust performance in target tracking. The feasibility and effectiveness of the DSRE were further verified through ex vivo experiments. We posit that this novel system holds significant potential for clinical application in ESD surgeries.

Oligotrophic microbes are recruited to resist multiple global change factors in agricultural subsoils.

An increasing number of anthropogenic pressures can have negative effects on biodiversity and ecosystem functioning. However, our understanding of how soil microbial communities and functions in response to multiple global change factors (GCFs) is still incomplete, particularly in less frequently disturbed subsoils. In this study, we examined the impact of different levels of GCFs (0-9) on soil functions and bacterial communities in both topsoils (0-20 cm) and subsoils (20-40 cm) of an agricultural ecosystem, and characterized the intrinsic factors influencing community resistance based on microbial life history strategy. Our experimental results showed a decline in soil multifunctionality, bacterial diversity, and community resistance as the number of GCFs increased, with a more drastic reduction in community resistance of subsoils. Specifically, we observed a significantly positive relationship between the oligotroph/copiotroph ratio and community resistance in subsoils, which was also verified by the negative correlation between 16S rRNA operon (rrn) copy number and community resistance. Structural equation modeling further revealed the direct effects of community resistance in promoting the ecosystem functioning, regardless of top- and subsoils. Therefore, these results suggested that subsoils may recruit more oligotrophic microbes to enhance their originally weaker community resistance under multiple GCFs, which was essential for maintaining sustainable agroecological functions and services. Overall, our study represents a significant advance in linking microbial life history strategy to the resistance of belowground microbial community and functionality.

IDH1 mutation predicts seizure occurrence and prognosis in lower-grade glioma adults.

Epileptic seizures are frequently the first symptom in glioma patients. However, the causal relationship between glioma and epilepsy is not yet fully understood, as it cannot be explained solely by tumor mass effect or peritumoral factors. In this study, we retrospectively enrolled 320 patients with grade 2-4 glioma who received treatment between January 2019 and July 2022, and explored the biomarkers of seizure occurrence and seizure outcome prediction using univariate and multivariate logistic regression analyses. Our results showed that IDH1 R132H mutation was an independent risk factor for seizure occurrence in lower-grade glioma (LGG) patients (OR = 4.915, 95%CI = 1.713 - 14.103, P = 0.003). Additionally, IDH1 R132H mutation predicted higher seizure-free ratios in LGG patients with intact ATRX expression (OR = 6.793, 95%CI = 1.217 - 37.923, P = 0.029) one year after diagnosis. Therefore, our findings suggest that IDH1 mutation can predict seizure occurrence and control in LGG patients, providing further insights into the relationship between glioma and epilepsy.

Tidal Variations of Fish Larvae Measured Using a 15-Day Continuous Ichthyoplankton Survey in Subei Shoal: Management Implications for the Red-Crowned Crane (Grus japonensis) Population in Yancheng Nature Reserve.

The National Yancheng Rare Birds Nature Reserve is a vitally important staging habitat for the wild population of red-crowned cranes (Grus japonensis) in China. The population relies on local high-protein food sources, such as fish juveniles, to fuel their migratory journeys. However, little is known about the ecology of the fish larvae and juveniles that migrate to the inshore area via tidal rhythm in Subei Shoal, which is adjacent to the reserve. Therefore, we used a fixed study station (32°55'1.2″ N, 121°19'58.8″ E) to conduct a continuous 15-day ichthyoplankton survey at 2 h intervals beginning at 05:00 on 25 April and ending at 03:00 on 10 May 2019. We identified the tidal variations in the number of fish larvae and juveniles and the number at various developmental stages and assessed how they were related to environmental variables such as sea surface temperature, salinity, turbidity, and tidal height in the Dafeng Sea area of Subei Shoal. We found that the number of species and larval individuals were highest and lowest, respectively, at the highest and lowest tidal height, and they obviously increased and decreased with the rising and ebb tide, respectively. Our findings indicate that the variation in numbers of the larvae and juveniles depends on species and developmental stage. The species Acanthogobius ommaturus, Pholis fangi, Cynoglossus joyneri, Liza haematocheila, and Lateolabrax japonicus and the total number of larvae were most influenced by tidal height. These results provide a better understanding of the habitat of prey species of the red-crowned crane wild population as well as scientific data that can be applied to manage the wild population in the reserve sustainably.

Alterations of regional spontaneous brain activity in obsessive-compulsive disorders: A meta-analysis.

BACKGROUND: Recent studies using resting-state functional magnetic resonance imaging (rs-fMRI) demonstrate that there is aberrant regional spontaneous brain activity in obsessive-compulsive disorders (OCD). Nevertheless, the results of previous studies are contradictory, especially in the abnormal brain regions and the directions of their activities. It is necessary to perform a meta-analysis to identify the common pattern of altered regional spontaneous brain activity in patients with OCD. METHODS: The present study conducted a systematic search for studies in English published up to May 2023 in PubMed, Web of Science, and Embase. These studies measured differences in regional spontaneous brain activity at the whole brain level using regional homogeneity (ReHo), the amplitude of low-frequency fluctuations (ALFF) and the fractional amplitude of low-frequency fluctuations (fALFF). Then the Anisotropic effect-size version of seed-based d mapping (AES-SDM) was used to investigate the consistent abnormality of regional spontaneous brain activity in patients with OCD. RESULTS: 27 studies (33 datasets) were included with 1256 OCD patients (650 males, 606 females) and 1176 healthy controls (HCs) (588 males, 588 females). Compared to HCs, patients with OCD showed increased spontaneous brain activity in the right inferior parietal gyrus (Brodmann Area 39), left median cingulate and paracingulate gyri (Brodmann Area 24), bilateral inferior cerebellum, right middle frontal gyrus (Brodmann Area 46), left inferior frontal gyrus in triangular part (Brodmann Area 45) and left middle frontal gyrus in orbital part (Brodmann Area 11). Meanwhile, decreased spontaneous brain activity was identified in the right precentral gyrus (Brodmann Area 4), right insula (Brodmann Area 48), left postcentral gyrus (Brodmann Area 43), bilateral superior cerebellum and left caudate (Brodmann Area 25). CONCLUSIONS: This meta-analysis provided a quantitative review of spontaneous brain activity in OCD. The results demonstrated that the brain regions in the frontal lobe, sensorimotor cortex, cerebellum, caudate and insula are crucially involved in the pathophysiology of OCD. This research contributes to the understanding of the pathophysiologic mechanism underlying OCD and could provide a new perspective on future diagnosis and treatment of OCD.

Agricultural tillage practice and rhizosphere selection interactively drive the improvement of soybean plant biomass.

Rhizosphere microbes play key roles in plant growth and productivity in agricultural systems. One of the critical issues is revealing the interaction of agricultural management (M) and rhizosphere selection effects (R) on soil microbial communities, root exudates and plant productivity. Through a field management experiment, we found that bacteria were more sensitive to the M × R interaction effect than fungi, and the positive effect of rhizosphere bacterial diversity on plant biomass existed in the bacterial three two-tillage system. In addition, inoculation experiments demonstrated that the nitrogen cycle-related isolate Stenotrophomonas could promote plant growth and alter the activities of extracellular enzymes N-acetyl- d-glucosaminidase and leucine aminopeptidase in rhizosphere soil. Microbe-metabolites network analysis revealed that hubnodes Burkholderia-Caballeronia-Paraburkholderia and Pseudomonas were recruited by specific root metabolites under the M × R interaction effect, and the inoculation of 10 rhizosphere-matched isolates further proved that these microbes could promote the growth of soybean seedlings. Kyoto Encyclopaedia of Genes and Genomes pathway analysis indicated that the growth-promoting mechanisms of these beneficial genera were closely related to metabolic pathways such as amino acid metabolism, melatonin biosynthesis, aerobactin biosynthesis and so on. This study provides field observation and experimental evidence to reveal the close relationship between beneficial rhizosphere microbes and plant productivity under the M × R interaction effect.

High-throughput sperm DNA analysis at the single-cell and population levels.

Clinical semen quality assessment is critical to the treatment of infertility. Sperm DNA integrity testing provides critical information that can steer treatment and influence outcomes and offspring health. Flow cytometry is the gold standard approach to assess DNA integrity, but it is not commonly applied at the clinical level. The sperm chromatin dispersion (SCD) assay provides a simpler and cheaper alternative. However, SCD is low-throughput and non-quantitative - sperm assessment is serial, manual and suffers inter- and intra-observer variations. Here, an automated SCD analysis method is presented that enables quantitative sperm DNA quality assessment at the single-cell and population levels. Levering automated optical microscopy and a chromatin diffusion-based analysis, a sample of thousands of sperm that would otherwise require 5 hours is assessed in under 10 minutes - a clinically viable workflow. The sperm DNA diffusion coefficient (DDNA) measurement correlates (R2 = 0.96) with DNA fragmentation index (DFI) from the cytometry-based sperm chromatin structure assay (SCSA). The automated measurement of population-level sperm DNA fragmentation (% sDF) prevents inter-observer variations and shows a good agreement with the SCSA % DFI (R2 = 0.98). This automated approach standardizes and accelerates SCD-based sperm DNA analysis, enabling the clinical application of sperm DNA integrity assessment.

Protocol of a prospective multicenter randomized controlled trial of robot-assisted stereotactic lesioning in the treatment of focal drug-resistant epilepsy.

BACKGROUND: This protocol describes the design of a multicenter randomized controlled trial of robot-assisted stereotactic lesioning versus epileptogenic foci resection. Typical causes of focal epilepsy include hippocampal sclerosis and focal cortical dysplasia. These patients usually present with drug resistance and require surgical treatment. Although epileptogenic foci resection is still the most commonly used treatment for such focal epilepsy, there is increasing evidence that epileptogenic focus resection may lead to neurological impairment. The treatment of epilepsy with a robot-assisted stereotactic lesioning mainly includes two new minimally invasive surgical methods: radiofrequency thermocoagulation (RF-TC) and laser interstitial thermal therapy (LITT). Seizure-free is less likely to be achieved by these two procedures, but neurologic preservation is better. In this study, we aimed to compare the safety and efficacy of RF-TC, LITT, and epileptogenic foci resection for focal drug-resistant epilepsy. METHODS: This is a multicenter, three-arm, randomized controlled clinical trial. The study will include patients older than 3 years of age with epilepsy who have had medically refractory seizures for at least 2 years and are eligible for surgical treatment with an epileptogenic focus as determined by multidisciplinary evaluation prior to randomization. The primary outcome measure is seizure outcome (quantified by seizure remission rate) at 3-month, 6-month, and 1-year follow-up after treatment. Postoperative neurologic impairment, spectrum distribution change of video electroencephalogram, quality of life, and medical costs will also be assessed as secondary outcomes. TRIAL REGISTRATION: Chinese Clinical Trials Registry ChiCTR2200060974. Registered on June 14, 2022. The status of the trial is recruiting, and the estimated study completion date is December 31, 2024.

Dynamic signatures of microplastic distribution across the water column of Yangtze River Estuary: Complicated implication of tidal effects.

Riverine microplastic (MP) discharge into the ocean contributes greatly to global MP contamination, yet our understanding of this process remains primitive. To deepen our interpretation of the dynamic MP variation throughout the estuarine water columns, we sampled at Xuliujing, the saltwater intrusion node of the Yangtze River Estuary, over the course of ebb and flood tides in four seasons (July and October 2017, January and May 2018 respectively). We observed that the collision of downstream and upstream currents contributed to the high MP concentration and that the mean MP abundance fluctuated with the tide. A model of microplastics residual net flux (MPRF-MODEL), taking the seasonal abundance and vertical distribution of MP along with current velocity into consideration, was developed to predict the net flux of MP throughout the full water columns. 2154 ± 359.7 t/year of MP was estimated to flow into the East China Sea via the River in 2017-2018. Our study suggests that riverine MP flux can be overestimated due to reciprocating current carried MP from the estuary. Using the tidal and seasonal variation in MP distribution, we calculated the tide impact factor index (TIFI) for the Yangtze River Estuary to be between 38.11% and 58.05%. In summary, this study provides a baseline of MP flux research in the Yangtze River for similar tidal-controlled rivers and a contextual understanding of how to appropriately sample and accurately estimate in a dynamic estuary system. The redistribution of microplastics may be impacted by complex tide processes. Although not observed in this study, it may merit investigation.

Towards an Optimized Artificial Neural Network for Predicting Flow Stress of In718 Alloys at High Temperatures.

Artificial neural networks (ANNs) have been an important approach for predicting the value of flow stress, which is dependent on temperature, strain, and strain rate. However, there is still a lack of sufficient knowledge regarding what structure of ANN should be used for predicting metal flow stress. In this paper, we train an ANN for predicting flow stress of In718 alloys at high temperatures using our experimental data, and the structure of the ANN is optimized by comparing the performance of four ANNs in predicting the flow stress of In718 alloy. It is found that, as the size of the ANN increases, the ability of the ANN to retrieve the flow stress results from a training dataset is significantly enhanced; however, the ability to predict the flow stress results absent from the training does not monotonically increase with the size of the ANN. It is concluded that the ANN with one hidden layer and four nodes possesses optimized performance for predicting the flow stress of In718 alloys in this study. The reason why there exists an optimized ANN size is discussed. When the ANN size is less than the optimized size, the prediction, especially the strain dependency, falls into underfitting and fails to predict the curve. When the ANN size is less than the optimized size, the predicted flow stress curves with the temperature, strain, and strain rate will contain non-physical fluctuations, thus reducing their prediction accuracy of extrapolation. For metals similar to the In718 alloy, ANNs with very few nodes in the hidden layer are preferred rather than the large ANNs with tens or hundreds of nodes in the hidden layers.

Suitability changes of Citrus medica L. var. sarcodactylis Swingle, a medicine-food plants affected by climate warming using the optimized MaxEnt model.

Climatic variables are important conditions for plant growth, development and reproduction. Citrus medica L. var. sarcodactylis Swingle (Rutaceae: Citrus) is one of the traditional bulk Chinese medicinal materials in China with the effects of bacteriostasis, anti-inflammatory, anti-oxidation, anti-cancer cells, regulating the immun. Analyzing the impact of climate change on geographical distribution of C. medica L. var. sarcodactylis can provide strong support for its production layout and agricultural zoning. In our paper, MaxEnt and ArcGIS were applied to simulate the suitable areas of C. medica L. var. sarcodactylis in China from the perspectives of bioclimate, soil, topographic factors and human activities, and the future climate scenarios generated by global climate models (GCMs) were selected to predict its suitable areas in 2050s and 2090s. Results showed that, 1) Under current climate condition, areas of the total, most, moderately and poorly suitable habitats of C. medica L. var. sarcodactylis in China were 177.36×104 km2, 22.27×104 km2, 51.96×104 km2 and 103.13×104 km2 respectively. The range of the most suitable habitat was the narrowest, which was located in the middle east of Sichuan, western Chongqing in the upstream of the Yangtze River Basin, southern Guizhou and western Guangxi in the upstream of the Pearl River Basin, central and southern Yunnan and Southeast Tibet in the Middle-Lower reaches of the Southwest River Basin and western Taiwan. 2) Under the future climate change scenarios, the total suitable area showed a significant increase trend in 2090s, and the change of most, moderately and poorly suitable habitats showed no obvious law. 3) Under SSP1-2.6, SSP2-4.5 and SSP5-8.5 scenarios, the centroid of the most suitable habitat of C. medica L. var. sarcodactylis would move to the northwest, southeast and southwest respectively.

Hypochlorous Acid and Chloramines Induce Specific Fragmentation and Cross-Linking of the G1-IGD-G2 Domains of Recombinant Human Aggrecan, and Inhibit ADAMTS1 Activity.

Atherosclerosis is a chronic inflammatory disease and a leading cause of mortality. It is characterized by arterial wall plaques that contain high levels of cholesterol and other lipids and activated leukocytes covered by a fibrous cap of extracellular matrix (ECM). The ECM undergoes remodelling during atherogenesis, with increased expression of aggrecan, a proteoglycan that binds low-density-lipoproteins (LDL). Aggrecan levels are regulated by proteases, including a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1). Activated leukocytes release myeloperoxidase (MPO) extracellularly, where it binds to proteins and proteoglycans. Aggrecan may therefore mediate colocalization of MPO and LDL. MPO generates hypochlorous acid (HOCl) and chloramines (RNHCl species, from reaction of HOCl with amines on amino acids and proteins) that damage LDL and proteins, but effects on aggrecan have not been examined. The present study demonstrates that HOCl cleaves truncated (G1-IGD-G2) recombinant human aggrecan at specific sites within the IGD domain, with these being different from those induced by ADAMTS1 which also cleaves within this region. Irreversible protein cross-links are also formed dose-dependently. These effects are limited by the HOCl scavenger methionine. Chloramines including those formed on amino acids, proteins, and ECM materials induce similar damage. HOCl and taurine chloramines inactivate ADAMTS1 consistent with a switch from proteolytic to oxidative aggrecan fragmentation. Evidence is also presented for colocalization of aggrecan and HOCl-generated epitopes in advanced human atherosclerotic plaques. Overall, these data show that HOCl and chloramines can induce specific modifications on aggrecan, and that these effects are distinct from those of ADAMTS1.