Gut microbial dysbiosis and alteration of microbial metabolites in Parkinson's disease (PD) have been increasingly reported. Dysbiosis in the composition and abundance of gut microbiota can affect ...both the enteric nervous system and the central nervous system (CNS), indicating the existence of a microbiota-gut-brain axis and thereby causing CNS diseases. Disturbance of the microbiota-gut-brain axis has been linked to specific microbial products that are related to gut inflammation and neuroinflammation. Future directions should therefore focus on the exploration of specific gut microbes or microbial metabolites that contribute to the development of PD. Microbiota-targeted interventions, such as antibiotics, probiotics and fecal microbiota transplantation, have been shown to favorably affect host health. In this review, recent findings regarding alterations and the role of gut microbiota and microbial metabolites in PD are summarized, and potential molecular mechanisms and microbiota-targeted interventions in PD are discussed.
Accurately characterizing spatiotemporal changes in surface urban heat islands (SUHIs) is a prerequisite for sustainable urban development. Although urban administrative boundaries have typically ...been used for SUHI modeling, they are inaccurate, because urban main built-up areas (UMBAs) are not well characterized. In this study, we developed an UMBA extraction method based on impervious surface distribution density (ISDD), to better differentiate suburban boundaries and ensure the integrity of land cover types. Additionally, we propose a new intensity classification method to analyze SUHI spatial distribution and variation. The UMBA was extracted using LANDSAT-8 data, and the temporal dynamics of SUHI intensity (i.e., daily, monthly, seasonal, and yearly changes) were extracted from MODIS data. A case study for Beijing showed that the mean daytime and nocturnal SUHI intensities vary at multiple time scales. In the daytime, SUHI intensities in Beijing UMBA were mainly level-2 and level-3, with central-south Beijing, a high incidence area, at level-3 in spring and summer. At night, with the rise of SUHI intensity levels, the frequency of SUHI intensity levels increased from the periphery to the center within the same season. ISDD had a marked influence on the frequency of SUHI intensity levels during the daytime, and the frequencies of level-1 to level-4 intensities increased with ISDD. This influence tended to weaken when ISDD exceeded 50%.
•Urban main built-up area was extracted by impervious surface distribution density.•An urban heat island intensity classification method was used to measure intensity.•Impervious surface distribution density has relationship with SUHI intensity level.
Activation-induced cytidine deaminase (AID)-single-strand (ss)DNA binding mode determines both microscale WRC preference and mesoscale complementarity determining region (CDR) preference; ...apolipoprotein B editing complex (APOBEC3)A uses a distinct binding mode and shows different DNA sequence preferences.The flexible ssDNA are AID-favored substrates in vitro and in vivo.Chromatin loop extrusion, superenhancer, and transcription stalling create a hierarchical order for AID deamination in chromatin loop domains.5-Hydroxymethylcytosine binding, ES cell specific (HMCES) is the factor that prevents AID lesions from processing into double-strand breaks in somatic hypermutation (SHM).Aberrant SHM directly regulates oncogene expression in lymphomagenesis, and promotes cell growth for a fraction of B cells expressing autoantibodies.A safer base editor could be designed based on the knowledge of AID-lesion repair.
Activation-induced cytidine deaminase (AID) initiates somatic hypermutation (SHM) by introducing base substitutions into antibody genes, a process enabling antibody affinity maturation in immune response. How a mutator is tamed to precisely and safely generate programmed DNA lesions in a physiological process remains unsettled, as its dysregulation drives lymphomagenesis. Recent research has revealed several hidden features of AID-initiated mutagenesis: preferential activity on flexible DNA substrates, restrained activity within chromatin loop domains, unique DNA repair factors to differentially decode AID-caused lesions, and diverse consequences of aberrant deamination. Here, we depict the multifaceted regulation of AID activity with a focus on emerging concepts/factors and discuss their implications for the design of base editors (BEs) that install somatic mutations to correct deleterious genomic variants.
Activation-induced cytidine deaminase (AID) initiates somatic hypermutation (SHM) by introducing base substitutions into antibody genes, a process enabling antibody affinity maturation in immune response. How a mutator is tamed to precisely and safely generate programmed DNA lesions in a physiological process remains unsettled, as its dysregulation drives lymphomagenesis. Recent research has revealed several hidden features of AID-initiated mutagenesis: preferential activity on flexible DNA substrates, restrained activity within chromatin loop domains, unique DNA repair factors to differentially decode AID-caused lesions, and diverse consequences of aberrant deamination. Here, we depict the multifaceted regulation of AID activity with a focus on emerging concepts/factors and discuss their implications for the design of base editors (BEs) that install somatic mutations to correct deleterious genomic variants.
Copper (Cu) nanowires (NWs) are inexpensive conducting nanomaterials intensively explored for transparent conducting electrodes and other applications. However, the mechanism for solution growth of ...Cu NWs remains elusive so far. Here we show that the one-dimensional anisotropic growth of Cu NWs and nanotubes (NTs) in solution is driven by axial screw dislocations. All three types of evidence for dislocation-driven growth have been conclusively observed using transmission electron microscopy (TEM) techniques: rigorous two-beam TEM analysis that conclusively characterizes the dislocations in the NWs to be pure screw dislocations along ⟨110⟩ direction, twist contour analysis that confirms the presence of Eshelby twist associated with the dislocation, and the observation of spontaneously formed hollow NTs. The reduction–oxidation (redox) electrochemical reaction forming the Cu NWs presents new chemistry for controlling supersaturation to promote dislocation-driven NW growth. Using this understanding to intentionally manipulate the supersaturation, we have further improved the NW growth by using a continuous flow reactor to yield longer Cu NWs under much milder chemical conditions. The rational synthesis of Cu NWs with control over size and geometry will facilitate their applications.
Lipid overload results in lipid redistribution among metabolic organs such as liver, adipose, and muscle; therefore, the interplay between liver and other organs is important to maintain lipid ...homeostasis. Here, we show that liver responds to lipid overload first and sends hepatocyte-derived extracellular vesicles (EVs) targeting adipocytes to regulate adipogenesis and lipogenesis. Geranylgeranyl diphosphate synthase (Ggpps) expression in liver is enhanced by lipid overload and regulates EV secretion through Rab27A geranylgeranylation. Consistently, liver-specific Ggpps deficient mice have reduced fat adipose deposition. The levels of several EV-derived miRNAs in the plasma of non-alcoholic fatty liver disease (NAFLD) patients are positively correlated with body mass index (BMI), and these miRNAs enhance adipocyte lipid accumulation. Thus, we highlight an inter-organ mechanism whereby the liver senses different metabolic states and sends corresponding signals to remodel adipose tissue to adapt to metabolic changes in response to lipid overload.
•The RSEI of the long time series is calculated by GEE.•Apply Theil-Sen-MK trend analysis to judge the long-term trend of RSEI.•Investigate the contribution of environment, human, and topography to ...RSEI changes.
The Yangtze River Basin has a wide range and complicated topography. In recent years, under the background of climate and land cover change, the ecological response of the whole ecological quality of the Yangtze River Basin is still unknown. To reveal the spatiotemporal changes in ecological quality in the Yangtze River Basin from 2001 to 2019 and their relationship with environmental and topographical factors, this study used the Google Earth Engine (GEE) platform to calculate the remote sensing ecological index (RSEI) based on the Moderate-resolution Imaging Spectroradiometer (MODIS) product image set, combined with the digital elevation data set and statistical yearbook. The data evaluated the ecological quality of the Yangtze River Basin and analyzed its causes. The results showed that: 1) the average RSEI of the Yangtze River Basin showed an overall upward trend, the growth rate was 0.027 (year−1), and the variation ranged from 0.5 to 0.568. The overall ecological quality rank was mainly neutral and slightly good. 2) The ecological quality of 85.7% of the Yangtze River Basin remains stable. A total of 11.2% of the regional ecological quality is improving, and 3.1% of the regional ecological quality is declining. Areas with reduced ecological quality are concentrated in the Hengduan Mountains. The dominant LST factor drives the deterioration of its ecological quality at a rate of −1.06 (year−1). The areas with improved ecological quality are concentrated in the upper and middle reaches of the Yangtze River. The dominant WET factor drives its ecological quality to improve at a rate of 0.27 (year−1). 3) From the perspective of topography, the ecological quality of the Yangtze River basin shows a wave-like decline and first rises and then falls in elevation and slope (the elevation is bounded by 2000 m and 6000 m, and the slope is bounded by 15°.). The average RSEI of the Yangtze River Basin is the highest on the northwest slope (0.554), and the ecological quality of sunny slopes is generally higher than that of shady slopes. The research shows that from 2001 to 2019, the overall ecological quality of the Yangtze River Basin has improved and evolved, but the ecological quality of the Hengduan Mountains has declined. Therefore, implementing different ecological protection policies in different regions is an important strategy for enhancing the stability of the ecosystem.
Plant communities in nature are often challenged by multiple global change factors (GCFs) and also ubiquitously encountered with soil nutrient heterogeneity. So far, however, we know little about the ...interactive effect of multiple GCFs and soil nutrient heterogeneity on plant communities. We conducted an outdoor mesocosm experiment in which a plant community was either grown in heterogeneous soils consisting of high‐ and low‐nutrient patches, or in homogeneous soils where the same amount of nutrients was evenly distributed. These plant communities were exposed to none (control), single, or a combination of two or four GCFs (i.e. drought, nitrogen deposition, microplastic and cadmium). Biomass of the plant community exposed to drought and nitrogen deposition were greater in heterogeneous than in homogeneous soils, but evenness of the plant community exposed to microplastics was lower. Increasing the number of GCFs increased community biomass more in heterogeneous than in homogeneous soils, but it generally reduced community evenness, independent of soil nutrient heterogeneity. These contrasting responses were related to changing competitive hierarchies and root foraging responses under different treatments. Our results suggest that soil nutrient heterogeneity can alter community productivity and diversity via changing competitive interactions of the component species, depending on both the identity and the number of GCFs acting on the community. These results have important implications for the maintenance of ecosystem functions and services under rapid and complex ongoing global changes.
The traditional one-liquid phase biofilter (OLPB), with water as the selected liquid phase, demonstrated low performance to volatile hydrophobic organic compounds. In this study, a novel two–liquid ...phase biofilter (TLPB) using silicone oil and water was established to treat gaseous dichloromethane (DCM). A comprehensive investigation of removal performance, kinetic analysis, biomass accumulations, pressure drops, CO2 productions, and microbial communities of the two biofilters was compared. Results showed that TLPB presented an average removal efficiency of 85% during 200 days of operation, which was higher than that of OLPB (63%). Owing to the buffering effects caused by silicone oil, TLPB demonstrated a superior fluctuation resistance capability than OLPB. TLPB was determined at a higher actual mass distribution coefficient of 6.00 than that of the OLPB (3.99), thereby suggesting a significantly more effective mass transfer process inside TLPB compared with that in OLPB. Furthermore, a rapid biomass accumulation process was observed in TLPB. The specific growth rates of biomass in OLPB and TLPB were calculated as 0.035 and 0.026 g of dry biomass/g of dry filter per day, respectively. The carbon balances were analyzed in the two biofilters. The yield coefficients (Y) were determined at 1.449 and 1.143 g of dry biomass/g of removed VOC for OLPB and TLPB, respectively. However, the corresponding CO2 production fraction was 0.263 g and 0.316 g per 1 g of DCM for OLPB and TLPB, respectively. The variations in fraction of carbon in DCM transformation to biomass and to CO2 suggested distinct microbial transformation pathways of utilizing DCM in the two biofilters, which were mainly caused by the different microbial communities and metabolic activities.
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•Two-liquid phase biofilter presented better performance than one-liquid phase biofilter.•TLPB showed superior fluctuation resistance capability due to buffering effects of silicone oil.•TLPB presented a different carbon transformation passway with OLPB.•TLPB demonstrated different microbial communities with OLPB.
Pancreatic ductal adenocarcinoma (PDAC) is an incurable cancer resistant to traditional treatments, although a limited number of early-stage patients can undergo radical resection. Immunotherapies ...for the treatment of haematological malignancies as well as solid tumours have been substantially improved over the past decades, and impressive results have been obtained in recent preclinical and clinical trials. However, PDAC is likely the exception because of its unique tumour microenvironment (TME). In this review, we summarize the characteristics of the PDAC TME and focus on the network of various tumour-infiltrating immune cells, outlining the current advances in PDAC immunotherapy and addressing the effect of the PDAC TME on immunotherapy. This review further explores the combinations of different therapies used to enhance antitumour efficacy or reverse immunodeficiencies and describes optimizable immunotherapeutic strategies for PDAC. The concordant combination of various treatments, such as targeting cancer cells and the stroma, reversing suppressive immune reactions and enhancing antitumour reactivity, may be the most promising approach for the treatment of PDAC. Traditional treatments, especially chemotherapy, may also be optimized for individual patients to remodel the immunosuppressive microenvironment for enhanced therapy.
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