Protists and fungi: Reinforcing urban soil ecological functions against flash droughts.

Rising instances of flash droughts are contributing to notable variability in soil moisture across terrestrial ecosystems. These phenomena challenge urban ecosystem services, yet the reaction of soil ecological functions (SEFs) to such events is poorly understood. This study investigates the responses of SEFs (about nutrient metabolism capacity and potential) and the microbiome under two specific scenarios: a flooding-drought sequence and a direct drought condition. Using quantitative microbial element cycling analysis, high-throughput sequencing, and enzyme activity measurements, we found that unlike in forests, the microbial composition in urban soils remained unchanged during flash drought conditions. However, SEFs were affected in both settings. Correlation analysis and Mantel test showed that forest soils exhibited more complex interactions among soil moisture, properties, and microbial communities. Positive linear correlation revealed that bacteria were the sole drivers of SEFs. Interestingly, while multi-threshold results suggested bacterial α diversity impeded the maximization of SEFs in urban soils, fungi and protists had a beneficial impact. Cross-domain network of urban soils had higher number of nodes and edges, but lower average degree and robustness than forest soils. Mantel test revealed that fungi and protist had significant correlations with bacterial composition in forest soils, but not in urban soils. In the urban network, the degree and eigenvector centrality of bacterial, fungal and protistan ASVs were significantly lower compared to those in the forest. These results suggest that the lower robustness of the microbial network in urban soils is attributed to limited interactions among fungi, consumer protists, and bacteria, contributing to the failure of microbial-driven ecological functions. Overall, our findings emphasize the critical role of fungi and protists in shielding urban soils from drought-induced disturbances and in enhancing the resistance of urban ecological functions amidst environmental changes.

Nitrogenous fertilizer plays a more important role than cultivars in shaping sorghum-associated microbiomes.

The plant microbiome plays a crucial role in facilitating plant growth through enhancing nutrient cycling, acquisition and transport, as well as alleviating stresses induced by nutrient limitations. Despite its significance, the relative importance of common agronomic practices, such as nitrogenous fertilizer, in shaping the plant microbiome across different cultivars remains unclear. This study investigated the dynamics of bacterial and fungal communities in leaf, root, rhizosphere, and bulk soil in response to nitrogenous fertilizer across ten sorghum varieties, using 16S rRNA and ITS gene amplicon sequencing, respectively. Our results revealed that nitrogen addition had a greater impact on sorghum-associated microbial communities compared to cultivar. Nitrogen addition significantly reduced bacterial diversity in all compartments except for the root endophytes. However, N addition significantly increased fungal diversity in both rhizosphere and bulk soils, while significantly reducing fungal diversity in the root endophytes. Furthermore, N addition significantly altered the community composition of bacteria and fungi in all four compartments, while cultivars only affected the community composition of root endosphere bacteria and fungi. Network analysis revealed that fertilization significantly reduced microbial network complexity and increased fungal-related network complexity. Collectively, this study provides empirical evidence that sorghum-associated microbiomes are predominantly shaped by nitrogenous fertilizer rather than by cultivars, suggesting that consistent application of nitrogenous fertilizer will ultimately alter plant-associated microbiomes regardless of cultivar selection.

The physicochemical properties of Cassava Starch/Carboxymethyl cellulose sodium edible film incorporated of Bacillus and its application in salmon fillet packaging.

Edible film is now a trend in the food packaging industry. In this study, edible films were prepared by adding two Bacillus spp. (Bacillus amyloliquefaciens Y11 and Bacillus velezensis Y12) to a cassava starch and carboxymethyl cellulose sodium matrix. The structural, physicochemical, and biological characteristics of the film were analyzed, and its application in salmon preservation was explored. The film had a dense structure and no pores, indicating that its polymeric components were compatible with each other. The addition of Bacillus spp. increased the antioxidant activity of the film and its ability to eliminate hydroxyl radicals (84.57% and 91.86%, respectively). The film also showed good antibacterial activity against several pathogens and underwent complete degradation in natural soil within 12 days. The film significantly reduced the total coliform count of salmon and extended its shelf life by 3 days, demonstrating its value as a food-packaging material.

Differentiation of cellular responses to particulate and soluble constituents in sunscreen products.

Despite the growing awareness of potential human and environmental risks associated with sunscreens, identifying the specific constituents responsible for their potential toxicity is challenging. In this study, we applied three different types of sunscreens with contrasting compositions and compared the effects of their particulate and soluble fractions based on 15 cellular biomarkers of HaCaT cells. Multilinear regression analysis revealed that the internalized soluble fractions played a primary role in the overall cytotoxicity of sunscreen mixtures, which was primarily attributed to their biotransformation, generating metabolites with higher toxicity. The presence of plastic microspheres in sunscreens either inhibited the internalization of soluble fractions or led to their redistribution toward lysosomes. Conversely, subcellular toxicity resulting from the sunscreen mixture was predominantly influenced by particulates. Bio-transformable particulates such as ZnO dissolved in the organelles and induced higher subcellular toxicity compared to bioinert particulates such as microplastics. Subcellular biomarkers including lysosomal count, lysosomal size, mitochondrial count and mitochondrial shape emerged as the potential predictors of sunscreen presence. Our study provides important understanding of sunscreen toxicity by elucidating the differential impacts of particulate and soluble fractions in mixture contaminants.

Inhibition of NLRP3 inflammasome alleviates cognitive deficits in a mouse model of anti-NMDAR encephalitis induced by active immunization.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a neurological disorder, characterized by cognitive deficits as one of its vital features. The nucleotide-binding oligomerization domain-like receptor (NLRP3) inflammasome is a key contributor to neuroinflammation and cognitive deficits in neurological diseases. However, the underlying mechanism of anti-NMDAR encephalitis remains unclear, and the biological function of the NLRP3 inflammasome in this condition has not been elucidated. In this study, a mouse model of anti-NMDAR encephalitis was induced by active immunization with the GluN1356-385 peptide (NEA model). The NLRP3 inflammasome in the hippocampus and temporal cortex was investigated using real-time quantitative PCR (RT-qPCR), western blotting, and immunofluorescence staining. The impact of MCC950 on cognitive function and NLRP3 inflammation was assessed. Confocal immunofluorescence staining and Sholl analysis were employed to examine the function and morphology of microglia. In the current study, we discovered overactivation of the NLRP3 inflammasome and an enhanced inflammatory response in the NEA model, particularly in the hippocampus and temporal cortex. Furthermore, significant cognitive dysfunction was observed in the NEA model. While, MCC950, a selective inhibitor of the NLRP3 inflammasome, sharply attenuated the inflammatory response in mice, leading to mitigated cognitive deficits of mice and more regular arrangements of neurons and reduced number of hyperchromatic cells were also observed in the hippocampus area. In addition, we found that the excess elevation of NLRP3 inflammasome was mainly expressed in microglia accompanied with the overactivation of microglia, while MCC950 treatment significantly inhibited the increased number and activated morphological changes of microglia in the NEA model. Altogether, our study reveals the vital role of overactivated NLRP3 signaling pathway in aggravating the inflammatory response and cognitive deficits and the potential protective effect of MCC950 in anti-NMDAR encephalitis. Thus, MCC950 represents a promising strategy for anti-inflammation in anti-NMDAR encephalitis and our study lays a theoretical foundation for it to become a clinically targeted drug.

Unveiling the luminescence property of Li2MgGeO4:Mn4+ featuring the tetrahedral crystallographic-site occupancy of Mn4.

Owing to the occupying tendency of Mn4+ at octahedral sites, doping Mn4+ activators in tetrahedral structures poses challenges and hence is seldom reported. In this work, tetrahedrally sited Mn4+ phosphors were studied. By combining X-ray diffraction (XRD) data with Rietveld refinement analysis, the location of Mn4+ was determined. It was found that by adding excessive raw MgO, the phosphor synthesis temperature can be improved, enhancing the crystallinity of the crystal and thus improving the emission performance of the phosphor. In addition, excessive raw MgO forms a second phase in an LMGO matrix, which does not change the doping site for Mn4+. The Tanabe-Sugano diagram of Mn4+ in the tetrahedral field and the energy-level diagram of these phosphors were constructed for the first time, and the excitation and emission mechanisms are discussed in detail. With 1.2-fold excess of raw MgO, the prepared sample (LMGO-Mn-1.2) shows the best luminescence, demonstrating red emissions peaked at 656 nm and affording an emission intensity enhancement of over 50 times compared to a stoichiometric LMGO:Mn4+ system. At 150 °C, LMGO-Mn-1.2 keeps 90% emission intensity compared to that at room temperature. Finally, a high-efficiency warm white light-emitting diode was built. This work provides new insights into the study of Mn4+-activated phosphors in a tetrahedron crystal field.

The miR-23b-3p from adipose-derived stem cell exosomes alleviate inflammation in mice experiencing kainic acid-induced epileptic seizures.

Epilepsy is a common neurologic disorder. While a good clinical solution is still missing, studies have confirmed that exosomes (Exos) derived from adipose-derived stem cells (ADSCs) had a therapeutic effect on various diseases, including neurological diseases. Therefore, this study aimed to reveal whether ADSC-Exo treatment could improve kainic acid (KA)-induced seizures in epileptic mice. ADSCs and Exos were isolated. Mice were generated with KA-induced epileptic seizures. ELISA was used to detect inflammatory factor expression. Luciferase reporter analysis detection showed a relationship among miR-23b-3p, STAT1, and glyoxylate reductase 1 (GlyR1). ADSC-Exos had a protective effect on KA-induced seizures by inhibiting inflammatory factor expression and the M1 microglia phenotype. The result showed that miR-23b-3p played an important role in the Exo-mediated protective effect in KA-induced seizures in epileptic mice by regulating STAT1 and GlyR1. Luciferase reporter analysis confirmed that miR-23b-3p interacted with the 3'-UTR of STAT1 and GlyR1. The miR-23b-3p inhibited M1 microglia-mediated inflammatory factor expression in microglial cells by regulating STAT1 and GlyR1. The downregulation of miR-23b-3p decreased the protective effect of ADSC-Exos on KA-induced seizures in epileptic mice. The miR-23b-3p from ADSC-Exos alleviated inflammation in mice with KA-induced epileptic seizures.

Unveiling the overlooked microbial niches thriving on building exteriors.

Rapid urbanization in the Asia-Pacific region is expected to place two-thirds of its population in concrete-dominated urban landscapes by 2050. While diverse architectural facades define the unique appearance of these urban systems. There remains a significant gap in our understanding of the composition, assembly, and ecological potential of microbial communities on building exteriors. Here, we examined bacterial and protistan communities on building surfaces along an urbanization gradient (urban, suburban and rural regions), investigating their spatial patterns and the driving factors behind their presence. A total of 55 bacterial and protist phyla were identified. The bacterial community was predominantly composed of Proteobacteria (33.7% to 67.5%). The protistan community exhibited a prevalence of Opisthokonta and Archaeplastida (17.5% to 82.1% and 1.8% to 61.2%, respectively). The composition and functionality of bacterial communities exhibited spatial patterns correlated with urbanization. In urban buildings, factors such as facade type, light exposure, and building height had comparatively less impact on bacterial composition compared to suburban and rural areas. The highest bacterial diversity and lowest Weighted Average Community Identity (WACI) were observed on suburban buildings, followed by rural buildings. In contrast, protists did not show spatial distribution characteristics related to facade type, light exposure, building height and urbanization level. The distinct spatial patterns of protists were primarily shaped by community diffusion and the bottom-up regulation exerted by bacterial communities. Together, our findings suggest that building exteriors serve as attachment points for local microbial metacommunities, offering unique habitats where bacteria and protists exhibit independent adaptive strategies closely tied to the overall ecological potential of the community.

Rapamycin alleviates mitochondrial dysfunction in anti-NMDAR encephalitis mice.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most prevalent forms of autoimmune encephalitis, characterized by a series of neurological and psychiatric symptoms, including cognitive impairment, seizures and psychosis. The underlying mechanism of anti-NMDAR encephalitis remains unclear. In the current study, the mouse model of anti-NMDAR encephalitis with active immunization was performed. We first uncovered excessive mitochondrial fission in the hippocampus and temporal cortex of anti-NMDAR encephalitis mice, indicated by elevated level of Phospho-DRP1 (Ser616) (p-Drp1-S616). Moreover, blockade of the autophagic flux was also demonstrated, leading to the accumulation of fragmented mitochondria, and elevated levels of mitochondrial reactive oxygen species (mtROS) and mitochondrial DNA (mtDNA) in anti-NMDAR encephalitis. More importantly, we found that the mTOR signaling pathway was overactivated, which could aggravate mitochondrial fission and inhibit autophagy, resulting in mitochondrial dysfunction. While rapamycin, the specific inhibitor of the mTOR signaling pathway, significantly alleviated mitochondrial dysfunction by inhibiting mitochondrial fission and enhancing autophagy. Levels of mtROS and mtDNA were markedly reduced after the treatment of rapamycin. In addition, rapamycin also significantly alleviated cognitive dysfunction and anxious behaviors found in anti-NMDAR encephalitis mice. Thus, our study reveals the vital role of mitochondrial dysfunction in pathological mechanism of anti-NMDAR encephalitis and lays a theoretical foundation for rapamycin to become a clinically targeted drug for anti-NMDAR encephalitis.

GSDMD mediated pyroptosis induced inflammation of Graves' orbitopathy via the NF-κB/ AIM2/ Caspase-1 pathway.

Gasdermin D (GSDMD) is a key executor which triggers pyroptosis as well as an attractive checkpoint in various inflammatory and autoimmune diseases but it has yet to prove its function in Graves'orbitopathy (GO). Our aim was to investigate GSDMD levels in orbital connective tissue and serum of GO patients and then assess the association between serum levels and patients' clinical activity score (CAS). Further, GSDMD-mediated pyroptosis and the underlying mechanism in inflammatory pathogenesis in the cultured orbital fibroblasts (OFs) of GO patients were examined. OFs were collected after tumor necrosis factor (TNF)-α or interferon (IFN)-γ treatment or combination treatment at different times, and the expression of GSDMD and related molecular mechanisms were analyzed. Then, we constructed the GSDMD knockout system with siRNA and the system was further exposed to the medium with or without IFN-γ and TNF-α for a specified time. Finally, we evaluated the production of interleukin (IL)-1ß and IL-18. We found that serum GSDMD levels were elevated and positively correlated with the CAS in GO patients. Meanwhile, the expression of GSDMD and N-terminal domain (NT-GSDMD) in orbital connective tissue of GO patients was augmented. Also, increased expression of GSDMD and related pyroptosis factors was observed in vitro model of GO. We further demonstrated that GSDMD-mediated pyroptosis induced inflammation via the nuclear factor kB (NF-κB)/absent in melanoma-2 (AIM-2)/caspase-1 pathway. In addition, blocking GSDMD suppressed proinflammatory cytokine production in GO. We concluded that GSDMD may be a biomarker as well as a potential target for the evaluation and treatment of inflammation related with GO.

National-scale investigation reveals the dominant role of phyllosphere fungal pathogens in sorghum yield loss.

Fungal plant pathogens threaten crop production and sustainable agricultural development. However, the environmental factors driving their diversity and nationwide biogeographic model remain elusive, impacting our capacity to predict their changes under future climate scenarios. Here, we analyzed potential fungal plant pathogens from 563 samples collected from 57 agricultural fields across China. Over 28.0% of fungal taxa in the phyllosphere were identified as potential plant pathogens, compared to 22.3% in the rhizosphere. Dominant fungal plant pathogen groups were Cladosporium (in the phyllosphere) and Fusarium (in the rhizosphere), with higher diversity observed in the phyllosphere than in rhizosphere soil. Deterministic processes played an important role in shaping the potential fungal plant pathogen community assembly in both habitats. Mean annual precipitation and temperature were the most important factor influencing phyllosphere fungal plant pathogen richness. Significantly negative relationships were found between fungal pathogen diversity and sorghum yield. Notably, compared to the rhizosphere, the phyllosphere fungal plant pathogen diversity played a more crucial role in sorghum yield. Together, our work provides novel insights into the factors governing the spatial patterns of fungal plant pathogens in the crop microbiome, and highlights the potential significance of aboveground phyllosphere fungal plant pathogens in crop productivity.

Reducing Gut Dissolution of Zinc Oxide Nanoparticles by Secondary Microplastics with Consequent Impacts on Barnacle Larvae.

The environmental impact of sunscreen is a growing concern, yet the combined effects of its components on marine animals are poorly understood. In this study, we investigated the combined effects of sunscreen-extracted zinc oxide nanoparticles (nZnO) and microplastics (MPs) on the development of barnacle larvae, focusing on the different roles played by primary microplastics (PMPs) and secondary microplastics (SMPs) generated through the phototransformation of PMPs. Our findings revealed that a lower concentration of nZnO (50 µg/L) enhanced molting and eye development in barnacle larvae, while a higher concentration (500 µg/L) inhibited larval growth. Co-exposure to PMPs had no significant effect on larval development, whereas SMPs mitigated the impact of nZnO by restricting the in vivo transformation to ionic Zn. Accumulated SMPs reduced gut dissolution of nZnO by up to 40%, lowering gut acidity by 85% and buffering the in vivo dissolution of nZnO. We further identified a rough-surfaced Si-5 fragment in SMPs that damaged larval guts, resulting in decreased acidity. Another Si-32 resisted phototransformation and had no discernible effects. Our study presented compelling evidence of the impacts of SMPs on the bioeffect of nZnO, highlighting the complex interactions between sunscreen components and their combined effects on marine organisms.

Aboveground plants determine the exchange of pathogens within air-phyllosphere-soil continuum in urban greenspaces.

The microbiome in the air-phyllosphere-soil continuum of urban greenspaces plays a crucial role in re-connecting urban populations with biodiverse environmental microbiomes. However, little is known about whether plant type affects the airborne microbiomes, as well as the extent to which soil and phyllosphere microbiomes contribute to airborne microbiomes. Here we collected soil, phyllosphere and airborne microbes with different plant types (broadleaf tree, conifer tree, and grass) in urban parks. Despite the significant impacts of plant type on soil and phyllosphere microbiomes, plant type had no obvious effects on the diversity of airborne microbes but shaped airborne bacterial composition in urban greenspaces. Soil and phyllosphere microbiomes had a higher contribution to airborne bacteria in broadleaf trees (37.56%) compared to conifer trees (9.51%) and grasses (14.29%). Grass areas in urban greenspaces exhibited a greater proportion of potential pathogens compared to the tree areas. The abundance of bacterial pathogens in phyllosphere was significantly higher in grasses compared to broadleaf and conifer trees. Together, our study provides novel insights into the microbiome patterns in air-phyllosphere-soil continuum, highlighting the potential significance of reducing the proportion of extensively human-intervened grass areas in future urban environment designs to enhance the provision of ecosystem services in urban greenspaces.

Prognostic value of circulating tumor cells associated with white blood cells in solid cancer: a systematic review and meta-analysis of 1471 patients with solid tumors.

BACKGROUND: The clinical relevance of circulating tumor cell-white blood cell (CTC-WBC) clusters in cancer prognosis is a subject of ongoing debate. This study aims to unravel their contentious predictive value for patient outcomes. METHODS: We conducted a comprehensive literature search of PubMed, Embase, and Cochrane Library up to December 2022. Eligible studies that reported survival outcomes and examined the presence of CTC-WBC clusters in solid tumor patients were included. Hazard ratios (HR) were pooled to assess the association between CTC-WBC clusters and overall survival (OS), as well as progression-free survival (PFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/recurrence-free survival (RFS). Subgroup analyses were performed based on sampling time, treatment method, detection method, detection system, and cancer type. RESULTS: A total of 1471 patients from 10 studies were included in this meta-analysis. The presence of CTC-WBCs was assessed as a prognostic factor for overall survival and PFS/DFS/MFS/RFS. The pooled analysis demonstrated that the presence of CTC-WBC clusters was significantly associated with worse OS (HR = 2.44, 95% CI: 1.74-3.40, P < 0.001) and PFS/DFS/MFS/RFS (HR = 1.83, 95% CI: 1.49-2.24, P < 0.001). Subgroup analyses based on sampling time, treatment method, detection method, detection system, cancer type, and study type consistently supported these findings. Further analyses indicated that CTC-WBC clusters were associated with larger tumor size (OR = 2.65, 95% CI: 1.58-4.44, P < 0.001) and higher alpha-fetoprotein levels (OR = 2.52, 95% CI: 1.50-4.22, P < 0.001) in hepatocellular carcinoma. However, no significant association was found between CTC-WBC clusters and TNM stage, depth of tumor invasion, or lymph node metastasis in the overall analysis. CONCLUSIONS: CTC-WBC clusters are negative predictors for OS and PFS/DFS/MFS/RFS in patients with solid tumors. Monitoring CTC-WBC levels may provide valuable information for predicting disease progression and guiding treatment decisions.

Precipitation seasonality and soil pH drive the large-scale distribution of soil invertebrate communities in agricultural ecosystems.

Soil invertebrates contribute significantly to vital ecosystem functions such as the breakdown of organic matter and cycling of essential nutrients, but our knowledge of their large-scale distribution in agricultural systems is limited, which hinders our ability to robustly predict how they will respond to future global change scenarios. Here, we employed metabarcoding analysis of eukaryotic 18S rRNA genes to examine the diversity and community composition of invertebrates in 528 sorghum rhizosphere and bulk soils, collected from 53 experimental field sites across China. Our results revealed that Nematoda, Arthropoda and Annelida were the dominant soil invertebrate groups in agroecosystems. Among all the climatic and soil parameters we examined, precipitation seasonality (i.e. the irregular distribution of precipitation during a normal year) had the strongest relationship with the richness of soil invertebrates, with an increase in soil invertebrate richness predicted with increasing precipitation seasonality. Mean annual precipitation and soil pH were the most important predictors of soil invertebrate community structure, with numerous invertebrate phylotypes showing either significantly positive or negative relationships with these two variables. Our findings suggest that shifts in precipitation patterns and soil pH, induced by future climate change and agricultural practices, will have important consequences for the distribution of soil invertebrate communities, with implications for agricultural ecosystem sustainability.

Flooding drives the temporal turnover of antibiotic resistance gene in manure-amended soil-water continuum.

Rice paddy soil is a hotspot of antibiotic resistance genes (ARGs) due to the application of organic fertilizers. However, the temporal dynamics of ARGs in rice paddy soil and its flooded water during the growing season remain underexplored. In this study, a microcosm experiment was conducted to explore the ARG profiles in a long term (130 days) flooded two-phase manure-amended soil-water system. By using high-throughput quantitative PCR array, a total of 23-98 and 34-85 ARGs were detected in the soil and overlying water, respectively. Regression analysis exhibited significant negative correlations between ARG profile similarities and flooding duration, indicating that flooding significantly altered the resistome (P < 0.001). This finding was validated by the increased ARG abundance in the soil and the overlying water, for example, after 130 days flooding, the abundance of ARGs in CK soil was increased from 0.03 to 1.20 copies per 16S rRNA. The PCoA analysis further suggested pig manure application resulted in distinct ARG profiles in the soil-water continuum compared with those of the non-amended control (Adonis, P < 0.05). The Venn diagram showed that all ARGs detected in the pig manure were present in the treated soil. Twelve ARGs (e.g., sul1) were shared among the pig manure, manure-amended soil, and overlying water, indicating that certain manure- or soil-borne ARGs were readily dispersed from the soil to the overlying water. Moreover, the enhanced relationships between the ARGs and mobile genetic elements in pig manure applied soil-water continuum indicate that the application of organic matter could accelerate the emergence and dissemination of ARGs. These findings suggested that flooding represents a crucial pathway for dispersal of ARGs from the soil to the overlying water. Identification of highly mobile ARGs in the soil-water continuum is essential for assessing their potential risk to human health and promoting the development of sustainable agricultural practices to mitigate their spread.

Periplocoside P affects synaptic transmission at the neuromuscular junction and reduces synaptic excitability in Drosophila melanogaster by inhibiting V-ATPase.

BACKGROUND: Periplocoside P (PSP) is a major component of Periploca sepium Bunge known for its potent insecticidal activity. V-Type adenosine triphosphatase (V-ATPase), which is widely distributed in the cytoplasmic membranes and organelles of eukaryotic cells, plays a crucial role in synaptic excitability conduction. Previous research has shown that PSP targets the apical membrane of goblet cells in the insect midgut. However, the effects of PSP on synaptic transmission at the neuromuscular junction are often overlooked. RESULTS: The bioassay revealed that Drosophila adults with different genetic backgrounds showed varying levels of susceptibility to PSP in the order: parats1 > parats1 ;DSC1-/- ≈ w1118 > DSC1-/- . Intracellular electrode recording demonstrated that PSP, similar to bafilomycin A1, had an impact on the amplitude of the excitatory junction potential (EJP) and accelerated excitability decay. Furthermore, the alteration in EJP amplitude is concentration-dependent. Another surprising discovery was that the knockout DSC1 channel showed insensitivity to PSP. CONCLUSION: Our findings confirm that PSP can influence synaptic transmission at the neuromuscular junction of Drosophila larvae by targeting V-ATPase. These results provide a basis for investigating the mechanism of action of PSP and its potential application in designing novel insecticides. © 2023 Society of Chemical Industry.

Serelaxin Alleviates Fibrosis in Thyroid-Associated Ophthalmopathy via the Notch Pathway.

Fibrosis is the late stage of thyroid-associated ophthalmopathy (TAO), resulting in serious complications. Effective therapeutic drugs are still lacking. We aimed to explore the mechanism of TAO fibrosis and to find a targeted drug. High-throughput RNA sequencing was performed on orbital connective tissues from twelve patients with TAO and six healthy controls. Protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and we identified the hub gene by Cytoscape software. Additionally, the RNA sequencing results were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatic prediction identified the functions of differentially expressed genes (DEGs). Further orbital connective tissue and serum samples of the TAO and control groups were collected for subsequent experiments. Histologic staining, Western blotting (WB), qRT-PCR, enzyme-linked immunosorbent assays (ELISAs), gene overexpression through lentiviral infection or silencing gene by short interfering RNA (siRNA) were performed. We found that the relaxin signaling pathway is an important regulatory pathway in TAO fibrosis pathogenesis. Serelaxin exerts antifibrotic and anti-inflammatory effects in TAO. Furthermore, the downstream Notch pathway was activated by serelaxin and was essential to the antifibrotic effect of serelaxin in TAO. The antifibrotic effect of serelaxin is dependent on RXFP1.

Photodegradation of Microplastics by ZnO Nanoparticles with Resulting Cellular and Subcellular Responses.

Both zinc oxide nanoparticles (ZnO NPs) and microplastics (MPs) were extracted from one commercial sunscreen, while other ingredients were removed based on the "like dissolves like" principle. MPs were further extracted by acidic digestion of ZnO NPs using HCl and characterized as spherical particles of approximately 5 µm with layered sheets in an irregular shape on the surface. Although MPs were stable in the presence of simulated sunlight and water after 12 h of exposure, ZnO NPs promoted the photooxidation by producing hydroxyl radicals, with a 2.5-fold increase in the carbonyl index of the degree of surface oxidation. As a result of surface oxidation, spherical MPs were more soluble in water and fragmented to irregular shapes with sharp edges. We then compared the cytotoxicity of primary MPs and secondary MPs (25-200 mg/L) to the HaCaT cell line based on viability loss and subcellular damages. The cellular uptake of MPs transformed by ZnO NPs was enhanced by over 20%, and MPs caused higher cytotoxicity compared with the pristine ones, as evidenced by a 46% lower cell viability, 220% higher lysosomal accumulation, 69% higher cellular reactive oxygen species, 27% more mitochondrial loss, and 72% higher mitochondrial superoxide at 200 mg/L. Our study for the first time explored the activation of MPs by ZnO NPs derived from commercial products and revealed the high cytotoxicity caused by secondary MPs, providing new evidence on the effects of secondary MPs on human health.

Clinical features of epileptic seizures in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes.

BACKGROUND AND PURPOSE: This study aimed to characterize the clinical features of epilepsy in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and analyze the clinical determinants for drug-resistant epilepsy in MELAS. METHODS: A single-center, retrospective study was conducted to investigate the clinical features of epilepsy in patients with MELAS. Collected variables included seizure semiology, electroencephalography (EEG), muscle biopsy, genetic testing, neuroimaging findings, resting serum lactic value and modified Rankin scale (mRS) of patients with MELAS. We also investigated the differences between the adult-onset group and the child-onset group and analyzed the risk factors for drug-resistant epilepsy in MELAS. RESULTS: We studied 97 patients (56 males: 41 females) with confirmed MELAS. Epileptic seizure occurred in 100.0% of patients and the initial symptom of 69.1% patients was epileptic seizure. The average age of disease onset was 21.0 years, ranging from 2 to 60 years. The seizure types of these patients with MELAS were variable, with generalized onset (51.5%) to be the most common type. The EEG changes in the patients with MELAS were mainly slow wave (90.9%) and epileptiform discharge (68.2%). The child-onset group with earlier seizure onset presented significantly higher resting serum lactic value (p = 0.0048) and lower incidence of stroke-like lesion in the brain (p = 0.003), especially in the temporal lobe (p < 0.001), compared with the adult-onset group. Importantly, drug-resistant epilepsy in MELAS was demonstrated to be closely related to the earlier age of seizure onset (p = 0.013), as well as the higher mRS score (p < 0.001) and higher resting serum lactic value (p = 0.009). CONCLUSION: Early identification of MELAS should be considered among individuals with recurrent epilepsy through clinical screening. Age of seizure onset and resting serum lactic value may predict the development of drug-resistant epilepsy in MELAS. Close observation and appropriate anti-epileptic treatment are indispensable for individuals with MELAS to improve the prognosis. Further studies with larger sample size are required to further evaluate the risk factors of drug-resistant epilepsy in MELAS and provide guidance on treatment of MELAS.