Abnormal white matter integrity of anterior-inferior hypothalamus in mild cognitive impairment patients with depression symptoms.

BACKGROUND: The hypothalamus is a key brain structure involved in the pathogenesis of depression, and its abnormal activity is considered an important pathological mechanism for the formation of depression. The presence of abnormalities in the white matter integrity of hypothalamic subregions in mild cognitive impairment with depressive symptoms (D-MCI) remains unknown. METHODS: In this study, we used diffusion tensor imaging (DTI) to explore the white matter integrity of hypothalamic subregions in D-MCI. On a 3 T magnetic resonance imaging scanner, we collected DTI data from 63 subjects. The subjects included 20 healthy controls (HC), 23 MCI patients without depression (nD-MCI), and 20 patients with D-MCI. The differences in DTI metrics of hypothalamic subregions of the three groups were compared using analysis of variance and post hoc t-tests. We looked at the relationship between clinical variables and DTI metrics in hypothalamus subregions using Pearson correlation analysis. RESULTS: Compared with nD-MCI and HC groups, D-MCI group showed increased fractional anisotropy (FA) in anterior-inferior hypothalamus. There was a weak negative correlation between FA values in the anterior-inferior hypothalamus and depression scores in D-MCI patients. CONCLUSIONS: Our findings suggest that depressive symptoms in MCI patients are associated with abnormal white matter integrity in the anterior-inferior hypothalamus.

The N545S and K717N substitution at the N-glycosylation sites of the S2 subunit of avian infectious bronchitis virus can significantly enhance viral pathogenicity.

The S2 subunit of infectious bronchitis virus (IBV) is a heavily glycosylated protein that can impact various characteristics of the virus. It is currently known that N-glycosylation modifications are predominantly located on the S2 subunit. However, the exact role of their N-glycosylation modification remains undisclosed. To elucidate the function of these N-glycosylation sites, we identified 14 common sites distributed on the S2 subunit of the 5 genotypes of IBV in present study. Subsequently, we selected 7 sites to generate mutants and assessed their impact on viral virulence, replication ability, and antigenicity. Our finding revealed that only 2 substitutions, N545S and K717N, increased the viral replication titer and antigenicity, and ultimately the pathogenicity in chicks. To delve into the mechanisms underlying this increased pathogenicity, we discovered that K717N can change the structure of antigenic epitopes. The N545S substitution not only influenced antigenic epitope structure, but also enhanced the ability of the virus to enter CEKs during the early stages of viral replication. These results suggest that the enhanced viral pathogenicity associated with N545S and K717N substitutions is multifaceted, with acceleration of the viral membrane fusion process and alterations in epitope structure representing crucial factors in the capability of N-glycosylation modifications to boost viral virulence. These insights provide valuable guidance for the efficient development of live attenuated vaccines.

Formation and culture of cell spheroids by using magnetic nanostructures resembling a crown of thorns.

In contrast to traditional two-dimensional (2D) cell-culture conditions, three-dimensional (3D) cell-culture models closely mimic complex in vivo conditions. However, constructing 3D cell culture models still faces challenges. In this paper, by using micro/nano fabrication method, including lithography, deposition, etching, and lift-off, we designed magnetic nanostructures resembling a crown of thorns. This magnetic crown of thorns (MCT) nanostructure enables the isolation of cells that have endocytosed magnetic particles. To assess the utility of this nanostructure, we used high-flux acquisition of Jurkat cells, an acute-leukemia cell line exhibiting the native phenotype, as an example. The novel structure enabled Jurkat cells to form spheroids within just 30 minutes by leveraging mild magnetic forces to bring together endocytosed magnetic particles. The size, volume, and arrangement of these spheroids were precisely regulated by the dimensions of the MCT nanostructure and the array configuration. The resulting magnetic cell clusters were uniform in size and reached saturation after 1400 seconds. Notably, these cell clusters could be easily separated from the MCT nanostructure through enzymatic digestion while maintaining their integrity. These clusters displayed a strong proliferation rate and survival capabilities, lasting for an impressive 96 hours. Compared with existing 3D cell-culture models, the approach presented in this study offers the advantage of rapid formation of uniform spheroids that can mimic in vivo microenvironments. These findings underscore the high potential of the MCT in cell-culture models and magnetic tissue enginerring.

The increased effective connectivity from left middle occipital gyrus to right medial septum/diagonal bands in AD patients after donepezil intervention.

Introduction: Donepezil enhances the function of cholinergic nerves by increasing the concentration of acetylcholine, thereby improving clinical symptoms in patients with Alzheimer's disease (AD). However, the neural mechanisms of how donepezil modulates the effective connectivity (EC) network of cholinergic system in AD patients remain unknown. We speculated that the effective network of the cholinergic system changes in AD patients after donepezil intervention. Methods: We employed resting-state functional magnetic resonance imaging and Granger causality analysis approach to explore changes in the effective connectivity network of the basal forebrain in AD patients before and after donepezil intervention. This study included 32 participants, including 16 healthy controls (HCs) and 16 AD patients. In a 3T MRI scanner, the 16 AD patients were scanned before and after the donepezil intervention. To compare EC differences between the three groups of participants, ANOVA and post-hoc t-tests analysis were employed. Results: Compared to baseline status, AD patients after donepezil intervention had an increased EC from left middle occipital gyrus to right medial septum/diagonal bands. Compared to HCs, AD patients after donepezil intervention had an increased EC from right inferior frontal gyrus/orbit part to right medial septum/diagonal bands, AD patients before donepezil intervention had a reduced EC from right precuneus to right medial septum/diagonal bands. A significant positive correlation was found between EC values in right precuneus and Mini-Mental State Examination in pre-intervention AD patients (r = 0.7338, p = 0.0012). Discussion: Our study showed that effective connectivity of brain regions associated with the default mode network in the cholinergic pathway was enhanced after donepezil intervention. The results of this study will help us to better understand the neural mechanisms of donepezil intervention in AD and to find clinical targets for intervention.

Predicting the efficacy of donepezil intervention in Alzheimer's disease patients using regional homogeneity in the inferior orbitofrontal cortex.

BACKGROUND: Although donepezil is a commonly used drug for treating Alzheimer's disease (AD), the mechanisms by which it affects patients' functional brain activity, and thus modulates clinical symptoms, remain unclear. METHODS: In the present study, we used resting-state functional magnetic resonance imaging (MRI) and regional homogeneity (ReHo) to investigate the effects of donepezil on local brain activity in AD patients. Resting-state functional MRI data were collected from 32 subjects: 16 healthy controls and 16 AD patients. All 16 AD patients underwent 6 months of donepezil treatment and received two MRI scans (pre- and post-intervention). Analysis of covariance and post hoc analyses were used to compare ReHo differences among the healthy controls, pre-intervention AD patients, and post-intervention AD patients. Pearson correlation analysis was used to examine relationships between ReHo values in differential brain regions and clinical symptoms. RESULTS: Compared with healthy controls, post-intervention AD patients had reduced ReHo in the orbital part of the inferior frontal gyrus, and pre-intervention AD patients had reduced ReHo in the orbital part of the right inferior frontal gyrus. Pattern recognition models revealed that pre-intervention ReHo values in abnormal brain regions of AD patients were 76% accurate for predicting the efficacy of donepezil on cognitive function and 65% accurate for predicting its efficacy on depressive symptoms. CONCLUSIONS: These findings deepen our understanding of the brain mechanisms underlying the clinical efficacy of donepezil in AD patients, and provide a novel way to predict its clinical efficacy in such patients.

Abnormally decreased functional connectivity of the right nucleus basalis of Meynert in Alzheimer's disease patients with depression symptoms.

Dysfunction of the basal forebrain is the main pathological feature in patients with Alzheimer's disease (AD). The aim of this study was to explore whether depressive symptoms cause changes in the functional network of the basal forebrain in AD patients. We collected MRI data from depressed AD patients (n = 24), nondepressed AD patients (n = 14) and healthy controls (n = 20). Resting-state functional magnetic resonance imaging data and functional connectivity analysis were used to study the characteristics of the basal forebrain functional network of the three groups of participants. The functional connectivity differences among the three groups were compared using ANCOVA and post hoc analyses. Compared to healthy controls, depressed AD patients showed reduced functional connectivity between the right nucleus basalis of Meynert and the left supramarginal gyrus and the supplementary motor area. These results increase our understanding of the neural mechanism of depressive symptoms in AD patients.

3D Printing of Individualized Microfluidic Chips with DLP-Based Printer.

Microfluidic chips have shown their potential for applications in fields such as chemistry and biology, and 3D printing is increasingly utilized as the fabrication method for microfluidic chips. To address key issues such as the long printing time for conventional 3D printing of a single chip and the demand for rapid response in individualized microfluidic chip customization, we have optimized the use of DLP (digital light processing) technology, which offers faster printing speeds due to its surface exposure method. In this study, we specifically focused on developing a fast-manufacturing process for directly printing microfluidic chips, addressing the high cost of traditional microfabrication processes and the lengthy production times associated with other 3D printing methods for microfluidic chips. Based on the designed three-dimensional chip model, we utilized a DLP-based printer to directly print two-dimensional and three-dimensional microfluidic chips with photosensitive resin. To overcome the challenge of clogging in printing microchannels, we proposed a printing method that combined an open-channel design with transparent adhesive tape sealing. This method enables the rapid printing of microfluidic chips with complex and intricate microstructures. This research provides a crucial foundation for the development of microfluidic chips in biomedical research.

Naturally derived highly resilient and adhesive hydrogels with application as surgical adhesive.

The inadequacy of conventional surgical techniques for wound closure and repair in soft and resilient tissues may lead to poor healing outcomes such as local tissue fibrosis and contracture. Therefore, the development of adhesive and resilient hydrogels that can adhere firmly to irregular and dynamic wound interfaces and provide a "tension-free proximity" environment for tissue regeneration has become extremely important. Herein, we describe an integrated modeling-experiment-application strategy for engineering a promising hydrogel-based bioadhesive based on recombinant human collagen (RHC) and catechol-modified hyaluronic acid (HA-Cat). Molecular modeling and simulations were used to verify and explore the hypothesis that RHC and HA-Cat can form an assembly complex through physical interactions. The complex was synergistically crosslinked via a catechol/o-quinone coupling reaction and a carbodiimide coupling reactions, resulting in superior hydrogels with strong adhesion and resilience properties. The application of this bioadhesive to tissue adhesion and wound sealing in vivo was successfully demonstrated, with an optimum collagen index, epidermal thickness, and lowest scar width. Furthermore, subcutaneous implantation demonstrated that the bioadhesive exhibited good biocompatibility and degradability. This newly developed hydrogel may be a highly promising surgical adhesive for medical applications, including wound closure and repair.

The lack of negative association between TE load and subgenome dominance in synthesized Brassica allotetraploids.

Polyploidization is important to the evolution of plants. Subgenome dominance is a distinct phenomenon associated with most allopolyploids. A gene on the dominant subgenome tends to express to higher RNA levels in all organs as compared to the expression of its syntenic paralogue (homoeolog). The mechanism that underlies the formation of subgenome dominance remains unknown, but there is evidence for the involvement of transposon/DNA methylation density differences nearby the genes of parents as being causal. The subgenome with lower density of transposon and methylation near genes is positively associated with subgenome dominance. Here, we generated eight generations of allotetraploid progenies from the merging of parental genomes Brassica rapa and Brassica oleracea. We found that transposon/methylation density differ near genes between the parental (rapa:oleracea) existed in the wide hybrid, persisted in the neotetraploids (the synthetic Brassica napus), but these neotetraploids expressed no expected subgenome dominance. This absence of B. rapa vs. B. oleracea subgenome dominance is particularly significant because, while there is no negative relationship between transposon/methylation level and subgenome dominance in the neotetraploids, the more ancient parental subgenomes for all Brassica did show differences in transposon/methylation densities near genes and did express, in the same samples of cells, biased gene expression diagnostic of subgenome dominance. We conclude that subgenome differences in methylated transposon near genes are not sufficient to initiate the biased gene expressions defining subgenome dominance. Our result was unexpected, and we suggest a "nuclear chimera" model to explain our data.

Research Note: A recombinant duck-derived H6N2 subtype avian influenza virus can replicate and shed in young chickens and cause disease.

The H6N2 subtype avian influenza virus (AIV) is commonly detected in the migratory waterfowl reservoirs. Previously, H6N2 AIV was believed to be nonpathogenic to young chickens and could not infect or shed in their respiratory tract under experimental conditions. However, in present study, a highly recombinant strain of duck-derived H6N2 AIV was discovered and isolated for pathogenicity tests. The results revealed that H6N2 could induce seroconversion in chickens and high morbidity of over 86.7%, along with evident upper respiratory tract hemorrhage. Moreover, 5 substitutions were detected in the upper respiratory tract shedding reisolated virus, with a high viral load in the target organs of infected chickens. In contrast, ducks failed to exhibit any symptoms, pathological lesions, or viral shedding, while demonstrated seroconversion and high viral load in the livers. These findings indicate that H6N2 AIV could also show pathogenicity to chickens under experimental conditions, thereby effectively replicating and shedding in chickens. Therefore, the study provides further elucidations on the pathogenicity of H6N2 AIV.

Collagen-Hyaluronic Acid Composite Hydrogels with Applications for Chronic Diabetic Wound Repair.

Chronic diabetic wounds have become a major healthcare challenge worldwide. Improper treatment may lead to serious complications. Current treatment methods including biological and physical methods and skin grafting have limitations and disadvantages, such as poor efficacy, inconvenience of use, and high cost. Therefore, developing a more effective and feasible treatment is of great significance for the repair of chronic diabetic wounds. Hydrogels can be designed to serve multiple functions to promote the repair of chronic diabetic wounds. Furthermore, 3D bioprinting enables hydrogel customization to fit chronic diabetic wounds, thus facilitating the healing process. This paper reports a study of 3D printing of a collagen-hyaluronic acid composite hydrogels with application for chronic diabetic wound repair. In situ printed hydrogels were developed by a macromolecular crosslinking network using methacrylated recombinant human collagen (RHCMA) and methacrylated hyaluronic acid (HAMA), both of which can respond to ultraviolet (UV) irradiation. The hydrogels were also loaded with silver nanoclusters (AgNCs) with ultra-small-size nanoparticles, which have the advantages of deep penetration ability and broad-spectrum high-efficiency antibacterial properties. The results of this study show that the developed RHCMA, HAMA, and AgNCs (RHAg) composite hydrogels present good UV responsiveness, porosity, mechanical properties, printability, and biocompatibility, all of which are beneficial to wound healing. The results of this study further show that the developed RHAg hydrogels not only effectively inhibited Staphylococcus aureus and Pseudomonas aeruginosa but also promoted the proliferation and migration of fibroblasts in vitro and tissue regeneration and collagen deposition in vivo, thus producing a desirable wound repair effect and can be used as an effective functional biomaterial to promote chronic diabetic wound repair.

Evolution of prevalent H9N2 subtype of avian influenza virus during 2019 to 2022 for the development of a control strategy in China.

The H9N2 subtype of avian influenza virus (H9N2 AIV) has caused significant losses in chicken flocks throughout China. At present, consensus has been reached that field isolates of H9N2 underwent antigenic drift to evolve into distinct groups with significant antigenic divergence from the commercially available vaccines in China. This project continues to monitor the evolution characteristics of H9N2 hemagglutinin (HA) genes in China over the past 3 yr. The results showed that the current circling H9N2 viruses were diversified into h9.4.2.5 subclade, which was genetically distant from commonly used commercial vaccine strains. Compared with vaccine strains or 2014 strains, more than 42.1% of the variable antigenic sites in recent 3 yr' strains have shown significant changes and these stacked changes have caused significant differences in antigenicity. We constructed a recombinant vaccine strain rCQY-GHHA, which uses A/Chicken/China/SichuanCQY/2014 as the framework and A/Chicken/China/SichuanGH/2020 strain, which meets the recent viral antigenic characteristics, as the HA gene donor. The recombinant strain was prepared as an oil-adjuvant inactivated vaccine following an industrial process. The results of the immune protection experiment showed that the rCQY-GHHA vaccine was better than the commercial vaccine strain SS in reducing the morbidity, pathological lesion, virus shedding, and viral load. These results provide a reference for the control of H9N2 AIV in China.

Altered functional connectivity of the locus coeruleus in Alzheimer's disease patients with depression symptoms.

Studies have shown that functional abnormalities in the locus coeruleus (LC) are strongly associated with depressive symptoms, but the pattern of LC functional connectivity in Alzheimer's disease patients with depressive symptoms (D-AD) remains unclear. The current study aimed to investigate the characteristics of LC functional connectivity (FC) in D-AD using resting-state functional magnetic resonance imaging (rsfMRI). We obtained rsfMRI data in 24 D-AD patients (aged 66-76 years), 14 non-depressive AD patients (nD-AD) (aged 69-79 years) and 20 normal controls (aged 67-74 years) using a 3 T scanner. We used the FC approach to investigate abnormalities in the LC brain network of D-AD patients. One-way ANCOVA and post-hoc two-sample t-tests were performed to compare the strength of functional connectivity from the LC among the three groups. Our results showed that, compared with normal controls, D-AD showed decreased left LC FC with the right caudate and left fusiform gyrus, whereas nD-AD showed decreased left LC FC with the right caudate, right middle frontal gyrus and left fusiform gyrus. Compared to nD-AD, D-AD showed increased left LC FC with right superior frontal gyrus and right precentral gyrus. These findings contribute to our understanding of the neural mechanisms of D-AD.

Coacervation-triggered hierarchically assembled hydrogels with application as surgical sealant.

Adhesive hydrogels possess great potential to be explored as tissue adhesives, surgical sealants, and hemostats. However, it has been a great challenge to develop hydrogels that can function rapidly and controllably on wet, dynamic biological tissues. Inspired by polyphenol chemistry, we introduce a coacervation-triggered shaping strategy that enables the hierarchical assembly of recombinant human collagen (RHC) and tannic acid (TA). The conformation of the RHC and TA aggregates is controlled to evolve from granular to web-like states, accompanied by the significant enhancement of mechanical and adhesion performance. The coacervation and assembly process is driven by intermolecular interactions, especially hydrogen bonding between RHC and TA. Benefitting from the multifaceted nature of polyphenol chemistry, the hierarchically assembled hydrogels revealed excellent properties as surgical sealing materials, including fast gelation time (within 10 s), clotting time (within 60 s), ultrastretchability (strain >10 000%), and tough adhesion (adhesive strength >250 kPa).In vivoexperiments demonstrated complete sealing of severely leaking heart and liver tissues with the assistance ofin situformed hydrogels during 7 d of follow-up. This work presents a highly promising hydrogel-based surgical sealant in wet and dynamic biological environments for future biomedical applications.

Alterations in Resting-State Interhemispheric Coordination With Refractory Auditory Verbal Hallucinations in Schizophrenia.

OBJECTIVE: The purpose of this study was to investigate resting-state interhemispheric functional connectivity in patients with schizophrenia and refractory auditory verbal hallucinations (RAVHs) by using voxel-mirrored homotopic connectivity (VMHC). METHODS: Thirty-four patients with schizophrenia and RAVHs (RAVH group), 23 patients with schizophrenia but no auditory verbal hallucinations (non-AVH group), and 28 matched healthy volunteers (healthy control group) were recruited in China. VMHC analyses were used to identify brain areas with significant differences in functional connectivity among the three groups, and correlations between symptom scores and neurological measures were examined. RESULTS: VMHC analyses showed aberrant bilateral connectivity between several homotopic brain regions: the RAVH and non-AVH groups showed differences in bilateral connectivity of the superior and middle temporal gyri, and the RAVH and healthy control groups showed differences in bilateral connectivity of the gyrus rectus, inferior frontal gyrus, and putamen. In addition, interhemispheric connectivity of the superior and middle temporal gyri correlated with patients' positive symptom scores. CONCLUSIONS: These findings may help to elucidate the pathophysiological mechanisms underlying auditory verbal hallucinations. The results revealed interhemispheric functional dysconnectivity among patients with schizophrenia and suggest that the dysconnectivity of homotopic brain regions may play an important role in the development of auditory verbal hallucinations.

Abnormal functional connectivity of the habenula in mild cognitive impairment patients with depression symptoms revealed by resting-state functional magnetic resonance imaging.

BACKGROUND: Recent research suggests that abnormalities in the habenula (HB), a core area of the brain that transmits reward information, may be a determinant of depression. However, it is not clear whether the functional connectivity (FC) pattern of the mild cognitive impairment (MCI) with and without depression symptoms is abnormal. METHODS: In this study, we used resting-state functional magnetic resonance imaging (fMRI) to examine the FC pattern of the HB in MCI patients with depression symptoms (D-MCI). We acquired fMRI data from 54 subjects on a 3T MRI. Subjects collected included 16 patients with D-MCI, 18 patients with MCI with no depression, and 20 healthy controls. One way ANCOVA and post hoc t-test were used to compare the difference in FC strength between the three groups. RESULTS: The D-MCI group had altered FC between the left HB and the right superior temporal gyrus, right inferior frontal gyrus/opercular part, and right middle frontal gyrus. The D-MCI group had increased FC between the right HB and precuneus. CONCLUSIONS: These results suggest that the dysfunction of the HB-Default model network might be involved in the neural mechanism underlying depression in MCI.

The Characteristics of Entorhinal Cortex Functional Connectivity in Alzheimer's Disease Patients with Depression.

BACKGROUND: Depression is one of the most common neuropsychiatric symptoms of Alzheimer's disease (AD) which decreases the life quality of both patients and caregivers. There are currently no effective drugs. It is therefore important to explore the pathogenesis of depression in AD patients. OBJECTIVE: The present study aimed to investigate the characteristics of the entorhinal cortex (EC) functional connectivity (FC) in the whole brain neural network of AD patients with depression (D-AD). METHODS: Twenty-four D-AD patients, 14 AD patients without depression (nD-AD), and 20 healthy controls underwent resting-state functional magnetic resonance imaging. We set the EC as the seed and used FC analysis. One-way analysis of variance was used to examine FC differences among the three groups. RESULTS: Using the left EC as the seed point, there were FC differences among the three groups in the left EC-inferior occipital gyrus. Using the right EC as the seed point, there were FC differences among the three groups in the right EC-middle frontal gyrus, -superior parietal gyrus, -superior medial frontal gyrus, and -precentral gyrus. Compared with the nD-AD group, the D-AD group had increased FC between the right EC and right postcentral gyrus. CONCLUSION: Asymmetry of FC in the EC and increased FC between the EC and right postcentral gyrus may be important in the pathogenesis of depression in AD.

The genome of Orychophragmus violaceus provides genomic insights into the evolution of Brassicaceae polyploidization and its distinct traits.

Orychophragmus violaceus, referred to as "eryuelan" (February orchid) in China, is an early-flowering ornamental plant. The high oil content and abundance of unsaturated fatty acids in O. violaceus seeds make it a potential high-quality oilseed crop. Here, we generated a whole-genome assembly for O. violaceus using Nanopore and Hi-C sequencing technologies. The assembled genome of O. violaceus was ∼1.3 Gb in size, with 12 pairs of chromosomes. Through investigation of ancestral genome evolution, we determined that the genome of O. violaceus experienced a tetraploidization event from a diploid progenitor with the translocated proto-Calepineae karyotype. Comparisons between the reconstructed subgenomes of O. violaceus identified indicators of subgenome dominance, indicating that subgenomes likely originated via allotetraploidy. O. violaceus was phylogenetically close to the Brassica genus, and tetraploidy in O. violaceus occurred approximately 8.57 million years ago, close in time to the whole-genome triplication of Brassica that likely arose via an intermediate tetraploid lineage. However, the tetraploidization in Orychophragmus was independent of the hexaploidization in Brassica, as evidenced by the results from detailed phylogenetic analyses and comparisons of the break and fusion points of ancestral genomic blocks. Moreover, identification of multi-copy genes regulating the production of high-quality oil highlighted the contributions of both tetraploidization and tandem duplication to functional innovation in O. violaceus. These findings provide novel insights into the polyploidization evolution of plant species and will promote both functional genomic studies and domestication/breeding efforts in O. violaceus.

Disrupted topological organization of functional brain networks in Alzheimer's disease patients with depressive symptoms.

BACKGROUND: Depression is a common symptom of Alzheimer's disease (AD), but the underlying neural mechanism is unknown. The aim of this study was to explore the topological properties of AD patients with depressive symptoms (D-AD) using graph theoretical analysis. METHODS: We obtained 3-Tesla rsfMRI data from 24 D-AD patients, 20 non-depressed AD patients (nD-AD), and 20 normal controls (NC). Resting state networks were identified using graph theory analysis. ANOVA with a two-sample t-test post hoc analysis in GRETNA was used to assess the topological measurements. RESULTS: Our results demonstrate that the three groups show characteristic properties of a small-world network. NCs showed significantly larger global and local efficiency than D-AD and nD-AD patients. Compared with nD-AD patients, D-AD patients showed decreased nodal centrality in the pallidum, putamen, and right superior temporal gyrus. They also showed increased nodal centrality in the right superior parietal gyrus, the medial orbital portion of the right superior frontal gyrus, and the orbital portion of the right superior frontal gyrus. Compared with nD-AD patients, NC showed decreased nodal betweenness in the right superior temporal gyrus, and increased nodal betweenness in medial orbital part of the right superior frontal gyrus. CONCLUSIONS: These results indicate that D-AD is associated with alterations of topological structure. Our study provides new insights into the brain mechanisms underlying D-AD.

Study of paraquat-induced pulmonary fibrosis using biomimetic micro-lung chips.

Paraquat (PQ) poisoning induces pulmonary fibrosisin vivo. The pathogenesis of pulmonary fibrosis is complex, which has prevented the development of specific treatments. Pulmonary fibrosis shows several characteristics including epithelial-mesenchymal transition (EMT), fibroblast activation, and extracellular matrix (ECM) deposition. To investigate pulmonary fibrosis, we designed a biomimetic multichannel micro-lung chip to imitate thein vivointerface between the lung epithelium and the lung interstitium. In our model, A549 (lung epithelial cells) and MRC-5 (fetal lung fibroblasts) cells were used to test the efficacy of our chip-based model. Rat tail type I collagen and hyaluronic acid were used to simulate ECM and to provide a 3D microenvironment. The micro-lung chips were cultured with PQ (0, 75, 150, 300, and 400µM). The viability of A549 and MRC-5 cells significantly decreased with increasing PQ concentrations. There were significant changes in surfactant proteins C (SP-C), alpha smooth muscle actin protein (α-SMA), and vimentin protein levels during PQ-induced pulmonary fibrosis. SP-C levels were decreased in A549 cells, while those ofα-SMA and vimentin were increased in A549 cells and MRC-5 cells treated with PQ in the micro-lung chip. We also designed a reference model without interaction between the lung epithelial cells and fibroblasts. Compared to the non-contact model, co-culturing A549 and MRC-5 cells in chips induced more severe EMT in A549 cells after treatment with 75µM PQ and together defended against PQ-induced damage. Thus, our novel co-culture micro-lung chip that models the lung epithelium and interstitium may provide a new approach for studying lung fibrosis and will facilitate drug development.