Respiratory protein-driven selectivity during the Permian-Triassic mass extinction.

Extinction selectivity determines the direction of macroevolution, especially during mass extinction; however, its driving mechanisms remain poorly understood. By investigating the physiological selectivity of marine animals during the Permian-Triassic mass extinction, we found that marine clades with lower O2-carrying capacity hemerythrin proteins and those relying on O2 diffusion experienced significantly greater extinction intensity and body-size reduction than those with higher O2-carrying capacity hemoglobin or hemocyanin proteins. Our findings suggest that animals with high O2-carrying capacity obtained the necessary O2 even under hypoxia and compensated for the increased energy requirements caused by ocean acidification, which enabled their survival during the Permian-Triassic mass extinction. Thus, high O2-carrying capacity may have been crucial for the transition from the Paleozoic to the Modern Evolutionary Fauna.

Probable Novel APP Met671Leu Mutation in a Chinese Han Family with Early-Onset Alzheimer's Disease.

Familial Alzheimer's disease (AD) is a rare disease caused by autosomal-dominant mutations. APP (encoding amyloid precursor protein), PSEN1 (encoding presenilin 1), and PSEN2 (encoding presenilin 2) are the most common genes cause dominant inherited AD. This study aimed to demonstrate a Chinese early-onset AD pedigree presenting as progressive memory impairment, apraxia, visual-spatial disorders, psychobehavioral disorders, and personality changes with a novel APP gene mutation. The family contains four patients, three carries and three normal family members. The proband underwent brain magnetic resonance imaging (MRI), 18F-fludeoxyglucose positron emission tomography (18F-FDG-PET), cerebrospinal fluid amyloid detection, 18F-florbetapir (AV-45) Positron Emission Computed Tomography (PET) imaging, whole-exome sequencing and Sanger sequencing. Brain MRI images showed brain atrophy, especially in the entorhinal cortex, temporal hippocampus, and lateral ventricle dilation. The FDG-PET showed hypometabolism in the frontotemporal, parietal, and hippocampal regions. 18F-florbetapir (AV-45) PET imaging showed cerebral cortex Aß protein deposition. The cerebrospinal fluid amyloid protein test showed Aß42/Aß40 ratio decreases, pathological phosphor-tau level increases. Whole-exome sequencing detected a new missense mutation of codon 671 (M671L), which was a heterozygous A to T point mutation at position 2011 (c.2011A > T) in exon 16 of the amyloid precursor protein, resulting in the replacement of methionine to Leucine. The co-separation analysis was validated in this family. The mutation was found in 3 patients, 3 clinical normal members in the family, but not in the other 3 unaffected family members, 100 unrelated normal subjects, or 100 sporadic patients with AD. This mutation was probably pathogenic and novel in a Chinese Han family with early-onset AD.

C-kit controls blood-brain barrier permeability by regulating caveolae-mediated transcytosis after chronic cerebral hypoperfusion.

Blood-brain barrier (BBB) dysfunction plays a pivotal role in the pathology of chronic cerebral hypoperfusion (CCH)-related neurodegenerative diseases. Continuous endothelial cells (EC) that line the blood vessels of the brain are important components of the BBB to strictly control the flow of substances and maintain the homeostatic environment of the brain. However, the molecular mechanisms from the perspective of EC-induced BBB dysfunction after CCH are largely unknown. In this study, the BBB function was assessed using immunostaining and transmission electron microscopy. The EC dysfunction profile was screened by using EC enrichment followed by RNA sequencing. After identified the key EC dysfunction factor, C-kit, we used the C-kit inhibition drug (imatinib) and C-kit down-regulation method (AAV-BR1-C-kit shRNA) to verify the role of C-kit on BBB integrity and EC transcytosis after CCH. Furthermore, we also activated C-kit with stem cell factor (SCF) to observe the effects of C-kit on BBB following CCH. We explored that macromolecular proteins entered the brain mainly through EC transcytosis after CCH and caused neuronal loss. Additionally, we identified receptor tyrosine kinase C-kit as a key EC dysfunction molecule. Furthermore, the pharmacological inhibition of C-kit with imatinib counteracted BBB leakage by reducing caveolae-mediated transcytosis. Moreover, treatment with AAV-BR1-C-kit shRNA, which targets brain EC to inhibit C-kit expression, also ameliorated BBB leakage by reducing caveolae-mediated transcytosis. Furthermore, the SCF increased the permeability of the BBB by actively increasing caveolae-mediated transcytosis. This study provides evidence that C-kit is a key BBB permeability regulator through caveolae-mediated transcytosis in EC after CCH.

Presenilin2 D439A Mutation Induces Dysfunction of Mitochondrial Fusion/Fission Dynamics and Abnormal Regulation of GTPase Activity.

Alzheimer's disease (AD) is an age-related progressive neurodegenerative disease, and approximately 10% of AD cases are early-onset familial AD (EOFAD), which is mainly linked to point mutations in genes encoding presenilins (PS1 and PS2). Mutations in PS2 are extremely rare and have not received enough attention. Recently, studies have found that Rho GTPase activity is closely related to the pathogenesis of AD. In this study, we used transcriptome sequencing in PS2 siRNA-transfected SH-SY5Y cells and found a group of differentially expressed genes (DEGs) related to the regulation of GTPase activity. Among those DEGs, the most significantly downregulated was Rho guanine nucleotide exchange factor 5 (ARHGEF5). GTPase activity in PS2 siRNA-transfected cells was significantly decreased. Then, we found that the expression of ARHGEF5 and the GTPase activity of Mitochondrial Rho GTPase 2 (Miro2) in PS2 D439A mutant SH-SY5Y cells were significantly decreased. We found for the first time that PS2 can bind to Miro2, and the PS2 D439A mutation reduced the binding between PS2 and Miro2, reduced the expression of Miro2, and resulted in an imbalance in mitochondrial fusion/fission dynamics. In conclusion, PS2 gene knockdown may participate in the pathogenesis of AD through the regulation of GTPase activity. The imbalance in mitochondrial dynamics mediated by the PS2 D439A mutation through regulation of the expression and GTPase activity of Miro2 may be a potential pathogenic mechanism of AD.

Impact of regional accessibility on urban residents' income in China: A bidirectional-fixed panel model.

The income gap between regions and its expansion are the main manifestations of the imbalanced and inadequate economic development in China. High-speed railway (HSR) construction is regarded as an important method to drive domestic demand, drive the pulse of the economy, and promote the coordinated development of regions. Based on the opening of HSR and the acceleration of ordinary railways, we used the weighted average travel time model and accessibility coefficient to estimate the changes on accessibility in 286 cities at prefecture-level and above from 2000 to 2018. Then, the influence mechanisms of improving regional accessibility on urban residents' income were estimated by using the bidirectional-fixed effects panel model and the recursive model respectively. We found that: (1) The accessibility of urban areas has been greatly improved due to the opening of HSR and the acceleration of ordinary railway, among which the improvement of HSR cities is greater. (2) The improvement of regional accessibility significantly promoted the income growth of urban residents, and the increase of the regional accessibility coefficient by 1 unit led to an average increase of 2140 yuan in the per capita disposable income of urban residents. (3) There is regional heterogeneity in the impact of improving regional accessibility on urban residents' income, and it has a significant effect on the eastern and northeastern regions. It has a greater positive effect on improving the income of residents in central cities compared with peripheral cities. (4) Regional accessibility can promote urban income growth through regional employment and fixed asset investment. In the future, the transportation network should be further improved to facilitate the regional economic cycle, strengthen the coordination and complementarity of regional economies, and promote regional economic integration so as to promote the improvement of resident income level and the common prosperity of the people.

Automatic identification and morphological comparison of bivalve and brachiopod fossils based on deep learning.

Fossil identification is an essential and fundamental task for conducting palaeontological research. Because the manual identification of fossils requires extensive experience and is time-consuming, automatic identification methods are proposed. However, these studies are limited to a few or dozens of species, which is hardly adequate for the needs of research. This study enabled the automatic identification of hundreds of species based on a newly established fossil dataset. An available "bivalve and brachiopod fossil image dataset" (BBFID, containing >16,000 "image-label" data pairs, taxonomic determination completed) was created. The bivalves and brachiopods contained in BBFID are closely related in morphology, ecology and evolution that have long attracted the interest of researchers. We achieved >80% identification accuracy at 22 genera and ∼64% accuracy at 343 species using EfficientNetV2s architecture. The intermediate output of the model was extracted and downscaled to obtain the morphological feature space of fossils using t-distributed stochastic neighbor embedding (t-SNE). We found a distinctive boundary between the morphological feature points of bivalves and brachiopods in fossil morphological feature distribution maps. This study provides a possible method for studying the morphological evolution of fossil clades using computer vision in the future.

Piezo1 transforms mechanical stress into pro senescence signals and promotes osteoarthritis severity.

Osteoarthritis (OA) is a prevalent disease among elderly people and is often characterized by chronic joint pain and dysfunction. Recently, growing evidence of chondrocyte senescence in the pathogenesis of OA has been found, and targeting senescence has started to be recognized as a therapeutic approach for OA. Piezo1, a mechanosensitive Ca2+ channel, has been reported to be harmful in sensing abnormal mechanical overloading and leading to chondrocyte apoptosis. However, whether Piezo1 can transform mechanical signals into senescence signals has rarely been reported. In this study, we found that severe OA cartilage expressed more Piezo1 and the senescence markers p16 and p21. 24 h of periodic mechanical stress induced chondrocyte senescence in vitro. In addition, we demonstrated the pivotal role of Piezo1 in OA chondrocyte senescence induced by mechanical stress. Piezo1 sensed mechanical stress and promoted chondrocyte senescence via its Ca2+ channel ability. Moreover, Piezo1 promoted SASP factors production under mechanical stress, particularly in IL-6 and IL-1ß. p38MAPK and NF-κB activation were two key pathways that responded to Piezo1 activation and promoted IL-6 and IL-1ß production, respectively. Collectively, our study revealed a connection between abnormal mechanical stress and chondrocyte senescence, which was mediated by Piezo1.

Long-Read Genome Sequencing of Abscondita cerata (Coleoptera: Lampyridae), the Endemic Firefly of Taiwan.

Abscondita cerata is the most abundant and widely distributed endemic firefly species in Taiwan and is considered a key environmental and ecological indicator organism. In this study, we report the first long-read genome sequencing of Abs. cerata sequenced by Nanopore technology. The draft genome size, 967 Mb, was measured through a hybrid approach that consisted of assembling using 11.25-Gb Nanopore long reads and polishing using 9.47-Gb BGI PE100 short reads. The drafted genome was assembled into 4,855 contigs, with the N50 reaching 325.269 kb length. The assembled genome was predicted to possess 55,206 protein-coding genes, of which 20,862 (37.78%) were functionally annotated with public databases. 47.11% of the genome sequences consisted of repeat elements; among them DNA transposons accounted for the largest proportion (26.79%). A BUSCO (Benchmarking Universal Single Copy Orthologs) evaluation demonstrated that the genome and gene completeness were 84.8% and 79%, respectively. The phylogeny constructed using 1,792 single copy genes was consistent with previous studies. The comparative transcriptome between adult male head and lantern tissues revealed (1) the vision of Abs. cerata is primarily UV-sensitive to environmental twilight, which determines when it begins its nocturnal activity, (2) the major expressed OR56d receptor may be correlated to suitable humidity sensing, and (3) Luc1-type luciferase is responsible for Abs. cerata's luminescent spectrum.

In Situ Precision Cell Electrospinning as an Efficient Stem Cell Delivery Approach for Cutaneous Wound Healing.

Mesenchymal stem cell (MSC) therapies have been brought forward as a promising treatment modality for cutaneous wound healing. However, current approaches for stem cell delivery have many drawbacks, such as lack of targetability and cell loss, leading to poor efficacy of stem cell therapy. To overcome these problems, in the present study, an in situ cell electrospinning system is developed as an attractive approach for stem cell delivery. MSCs have a high cell viability of over 90% even with a high applied voltage of 15 kV post-cell electrospinning process. In addition, cell electrospinning does not show any negative effect on the surface marker expression and differentiation capacity of MSCs. In vivo studies demonstrate that in situ cell electrospinning treatment can promote cutaneous wound healing through direct deposition of bioactive fish gelatin fibers and MSCs onto wound sites, leading to a synergic therapeutic effect. The approach enhances extracellular matrix remodeling by increasing collagen deposition, promotes angiogenesis by increasing the expression of vascular endothelial growth factor (VEGF) and forming small blood vessels, and dramatically reduces the expression of interleukin-6 (IL-6) during wound healing. The use of in situ cell electrospinning system potentially provides a rapid, no touch, personalized treatment for cutaneous wound healing.

Results after open lunate excision alone or in combination with palmaris longus tendon ball arthroplasty for the treatment of Kienböck's disease.

PURPOSE: This study aims to compare results after open lunate excision alone and in combination with palmaris longus tendon ball arthroplasty for the treatment of late-staged Kienböck's disease (KD). METHODS: This is a retrospective study using the prospectively collected data, and patients who had a discharge diagnosis of KD (stage IIIB based on Lichtman staging criteria) and underwent surgical treatment by lunate excision alone or in combination with palmaris longus tendon ball arthroplasty between January 2011 and December 2020 were included in this study. Variables of interest involved demographics, disease condition, operative procedure, and the outcomes evaluated at the last follow-up. Within and between comparisons were performed. RESULTS: Thirty-five patients underwent lunate excision alone, and 40 patients underwent the combination procedure. At the final follow-up, patients in both groups exhibited significant improvements compared to pre-operation, such as wrist flexion, wrist extension, carpal height ratio, PRWE score, Cooney score, and grip strength (all P < 0.05). Compared to the excision group, combination procedure group had significantly longer surgical time (P < 0.001), more blood loss (P < 0.001) and exhibited better wrist flexion (P = 0.001), PRWE score (P = 0.001), Cooney score (P = 0.0034), and grip strength (P = 0.017). The excellent or good rate based on Cooney wrist score was not significantly different (87.5% vs 71.4%, P = 0.083). CONCLUSION: Lunate excision in combination with palmaris longus tendon ball arthroplasty is a better option than lunate excision alone for the treatment of stage III KD and can be considered as an operative option.

Metabolic regulation and antihyperglycemic properties of diet-derived PGG through transcriptomic and metabolomic profiling.

Diabetes has become a significant disease threatening human health and social development. Food intervention is considered an essential strategy to prevent early diabetes development sustainably. The natural product, 1,2,3,4,6-penta-O-galloyl-ß-D-glucose (PGG), commonly found in fruits and diets, has many potential antihypoglycemic, antibacterial, and antitumor activities. We found that PGG can promote glucose uptake in whole-organism zebrafish screening, which help in downregulating the glucose levels. We investigated the metabolome and transcriptome changes in zebrafish exposed to high glucose and PGG intervention. The differential genes and metabolites were screened out based on the comparisons of blank, hyperglycemic, and the PGG-exposed groups of zebrafish larvae. Combined with RT-qPCR validation, we found that PGG mainly restored four genes (fthl27, LOC110438965, plat, and aacs) and six metabolites abnormally invoked by high glucose. These validated genes are related with the key metabolites sphingosine and (R)-3-hydroxybutanoate involving the pathways of apelin, apoptosis, necroptosis, and butanoate metabolism. Our findings provided a new mechanistic basis for understanding the hypoglycaemic function of the commonly present dietary molecule (PGG) and offered a new perspective for the rational utilization of PGG to regulate metabolic disorders.

Degradation of ammonia nitrogen by an economic combined hydrodynamic cavitation method.

Hydrodynamic cavitation (HC) was a kind of advanced oxidation mode. There were defects in the common HC devices, such as high energy consumption, low efficiency, and easy plugging. In order to effectively utilize HC, it was urgent to research new HC devices and used them together with other traditional water treatment methods. Ozone was widely used as a water treatment agent that does not produce harmful by-products. Sodium hypochlorite (NaClO) was efficient and cheap, but too much chlorine will be harmful to water. The combination of ozone and NaClO with the HC device of propeller orifice plate can improve the dissolution and utilization rate of ozone in wastewater, reduce the use of NaClO, and avoid the generation of residual chlorine. The degradation rate reached 99.9% when the mole ratio γ of NaClO to ammonia nitrogen (NH3-N) was 1.5 and the residual chlorine was near zero. As for the degradation rate of NH3-N or COD of actual river water and real wastewater after biological treatment, the ideal mole ratio γ was also 1.5 and the ideal O3 flow rates were 1.0 L/min. The combined method has been preliminarily applied to actual water treatment and was expected to be used in more and more scenarios.

A Chinese SCA36 pedigree analysis of NOP56 expansion region based on long-read sequencing.

Introduction: Spinocerebellar ataxias 36 (SCA36) is the neurodegenerative disease caused by the GGCCTG Hexanucleotide repeat expansions in NOP56, which is too long to sequence using short-read sequencing. Single molecule real time (SMRT) sequencing can sequence across disease-causing repeat expansion. We report the first long-read sequencing data across the expansion region in SCA36. Methods: We collected and described the clinical manifestations and imaging features of Han Chinese pedigree with three generations of SCA36. Also, we focused on structural variation analysis for intron 1 of the NOP56 gene by SMRT sequencing in the assembled genome. Results: The main clinical features of this pedigree are late-onset ataxia symptoms, with a presymptomatic presence of affective and sleep disorders. In addition, the results of SMRT sequencing showed the specific repeat expansion region and demonstrated that the region was not composed of single GGCCTG hexanucleotides and there were random interruptions. Discussion: We extended the phenotypic spectrum of SCA36. We applied SMRT sequencing to reveal the correlation between genotype and phenotype of SCA36. Our findings indicated that long-read sequencing is well suited to characterize known repeat expansion.

A Mesozoic fossil lagerstätte from 250.8 million years ago shows a modern-type marine ecosystem.

Finely preserved fossil assemblages (lagerstätten) provide crucial insights into evolutionary innovations in deep time. We report an exceptionally preserved Early Triassic fossil assemblage, the Guiyang Biota, from the Daye Formation near Guiyang, South China. High-precision uranium-lead dating shows that the age of the Guiyang Biota is 250.83 +0.07/-0.06 million years ago. This is only 1.08 ± 0.08 million years after the severe Permian-Triassic mass extinction, and this assemblage therefore represents the oldest known Mesozoic lagerstätte found so far. The Guiyang Biota comprises at least 12 classes and 19 orders, including diverse fish fauna and malacostracans, revealing a trophically complex marine ecosystem. Therefore, this assemblage demonstrates the rapid rise of modern-type marine ecosystems after the Permian-Triassic mass extinction.

VCAM1 Drives Vascular Inflammation Leading to Continuous Cortical Neuronal Loss Following Chronic Cerebral Hypoperfusion.

BACKGROUND: Chronic cerebral hypoperfusion (CCH) is associated with neuronal loss and blood-brain barrier (BBB) impairment in vascular dementia (VaD). However, the relationship and the molecular mechanisms between BBB dysfunction and neuronal loss remain elusive. OBJECTIVE: We explored the reasons for neuron loss following CCH. METHODS: Using permanent bilateral common carotid artery occlusion (2VO) rat model, we observed the pathological changes of cortical neurons and BBB in the sham group as well as rats 3d, 7d, 14d and 28d post 2VO. In order to further explore the factors influencing neuron loss following CCH with regard to cortical blood vessels, we extracted cortical brain microvessels at five time points for transcriptome sequencing. Finally, integrin receptor a4ß1 (VLA-4) inhibitor was injected into the tail vein, and cortical neuron loss was detected again. RESULTS: We found that cortical neuron loss following CCH is a continuous process, but damage to the BBB is acute and transient. Results of cortical microvessel transcriptome analysis showed that biological processes related to vascular inflammation mainly occurred in the chronic phase. Meanwhile, cell adhesion molecules, cytokine-cytokine receptor interaction were significantly changed at this phase. Among them, the adhesion molecule VCAM1 plays an important role. Using VLA-4 inhibitor to block VCAM1-VLA-4 interaction, cortical neuron damage was ameliorated at 14d post 2VO. CONCLUSION: Injury of the BBB may not be the main reason for persistent loss of cortical neurons following CCH. The continuous inflammatory response within blood vessels maybe an important factor in the continuous loss of cortical neurons following CCH.

Thiol-ene conjugation of VEGF peptide to electrospun scaffolds as potential application for angiogenesis.

Vascular endothelial growth factor (VEGF) plays a vital role in promoting attachment and proliferation of endothelial cells, and induces angiogenesis. In recent years, much research has been conducted on functionalization of tissue engineering scaffolds with VEGF or VEGF-mimetic peptide to promote angiogenesis. However, most chemical reactions are nonspecific and require organic solvents, which can compromise control over functionalization and alter peptide/protein activity. An attractive alternative is the fabrication of functionalizable electrospun fibers, which can overcome these hurdles. In this study, we used thiol-ene chemistry for the conjugation of a VEGF-mimetic peptide to the surface of poly (ε-caprolactone) (PCL) fibrous scaffolds with varying amounts of a functional PCL-diacrylate (PCL-DA) polymer. 30% PCL-DA was selected due to homogeneous fiber morphology. A VEGF-mimetic peptide was then immobilized on PCL-DA fibrous scaffolds by a light-initiated thiol-ene reaction. 7-Mercapto-4-methylcoumarin, RGD-FITC peptide and VEGF-TAMRA mimetic peptide were used to validate the thiol-ene reaction with fibrous scaffolds. Tensile strength and elastic modulus of 30% PCL-DA fibrous scaffolds were significantly increased after the reaction. Conjugation of 30% PCL-DA fibrous scaffolds with VEGF peptide increased the surface water wettability of the scaffolds. Patterned structures could be obtained after using a photomask on the fibrous film. Moreover, in vitro studies indicated that scaffolds functionalized with the VEGF-mimetic peptide were able to induce phosphorylation of VEGF receptor and enhanced HUVECs survival, proliferation and adhesion. A chick chorioallantoic membrane (CAM) assay further indicated that the VEGF peptide functionalized scaffolds are able to promote angiogenesis in vivo. These results show that scaffold functionalization can be controlled via a simple polymer mixing approach, and that the functionalized VEGF peptide-scaffolds have potential for vascular tissue regeneration.

A New Mechanism for Ginsenoside Rb1 to Promote Glucose Uptake, Regulating Riboflavin Metabolism and Redox Homeostasis.

Glucose absorption promoters perform insulin mimic functions to enhance blood glucose transport to skeletal muscle cells and accelerate glucose consumption, thereby reducing blood glucose levels. In our screening exploration of food ingredients for improving glucose transportation and metabolism, we found that the saponins in American ginseng (Panaxquinquefolius L.) showed potential activity to promote glucose uptake, which can be used for stabilizing levels of postprandial blood glucose. The aim of this study was to identify key components of American ginseng with glucose uptake-promoting activity and to elucidate their metabolic regulatory mechanisms. Bio-guided isolation using zebrafish larvae and 2-NBDG indicator identified ginsenoside Rb1 (GRb1) as the most potential promotor of glucose uptake. Using UPLC-QTOF-MS/MS combined with RT-qPCR and phenotypic verification, we found that riboflavin metabolism is the hinge for GRb1-mediated facilitation of glucose transport. GRb1-induced restoration of redox homeostasis was mediated by targeting riboflavin transporters (SLC52A1 and SLC52A3) and riboflavin kinase (RFK).

A simulation of acetate consumption and electricity generation in a single microbial fuel cell considering the diversity of nonelectrogenic bacteria.

To simulate acetate consumption and electricity generation in a cycle of a microbial fuel cell (MFC) treating synthetic acetate-based wastewater with low concentration, nonelectrogenic bacteria (NEB), which had no contribution in electricity generation, was incorporated with methanogen's kinetic parameters into a previous biofilm model proposed by Marcus et al. (Biotechnol Bioeng 98:1171-1182, 2007). However, the Coulombic efficiency was estimated to be 40.1%, whereas the experiment showed 13.6%, as the presence of NEB was obviously underestimated. Thus, the maximum NEB reaction rate (qmaxC) was temporarily calibrated, and a sensitivity analysis was then conducted. As a result, the growth parameters of NEB, the growth of the exoelectrogenic bacteria, and the biofilm detachment were identified as influential parameters. qmaxC and a half rate constant of NEB (KsC) were selected as potential calibration parameters. The two sets of calibrated parameters (0.342 mmol-acetate (Ac)/mg-volatile solids (VS)/d of qmaxC and 33.8 mg-carbon (C)/L of KsC; 0.274 mmol-Ac/mg-VS/d of qmaxC and 16.9 mg-C/L of KsC) showed a good agreement with the experimental results at 100 mg-C/L of initial acetate. However, the calibrated parameter values obviously differed from those in previous models. The calibrated model also showed good agreement with the experimental results at 50 and 200 mg-C/L of the initial acetate. In view of the different values of qmaxC and KsC from those of methanogenic bacteria in previous models and the previous findings on anode microbial community, which showed that NEB are not only methanogenic bacteria, we concluded that the diversity of NEB should be considered to simulate performances in a cycle of MFC treating low organic matter concentrations.

Effects of different regional cerebral blood flow on white matter hyperintensity in CADASIL patients.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an early-onset inherited small vessel disease. Decreased cerebral blood flow (CBF) may contribute to white matter hyperintensity (WMH) severity in CADASIL, but more evidence is needed to support this hypothesis. This study comprised six patients with CADASIL who harbored mutations in the coding sequence of NOTCH3 and twelve age-matched neurologically healthy controls. We collected clinical and imaging data from patients with CADASIL and divided the brain into four regions: WMH, normal-appearing white matter (NAWM), gray matter (GM), and global brain. We analyzed the relationship between CBF of each region and the WMH volume. Compared with the control group, CBF was significantly decreased in all four regions in the CADASIL group. Lower CBF in these regions was correlated with higher WMH volume in CADASIL. CBF in the NAWM, GM and global regions was positively correlated with that in WMH region. However, after correction tests, only CBF in the WMH region but not in NAWM, GM and global regions was associated with WMH volume. Our findings suggest that CBF in the WMH region is an influencing factor of the WMH severity in CADASIL.

Mechanisms regulating cerebral hypoperfusion in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Cerebral small vessel disease (CSVD) is a leading cause of stroke and dementia. As the most common type of inherited CSVD, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by the NOTCH3 gene mutation which leads to Notch3 ectodomain deposition and extracellular matrix aggregation around the small vessels. It further causes smooth muscle cell degeneration and small vessel arteriopathy in the central nervous system. Compromised cerebral blood flow occurs in the early stage of CADASIL and is associated with white matter hyperintensity, the typical neuroimaging pathology of CADASIL. This suggests that cerebral hypoperfusion may play an important role in the pathogenesis of CADASIL. However, the mechanistic linkage between NOTCH3 mutation and cerebral hypoperfusion remains unknown. Therefore, in this mini-review, it examines the cellular and molecular mechanisms contributing to cerebral hypoperfusion in CADASIL.