Discovery of 1,2,3-triazole-based pleuromutilin derivatives as potent gram-positive antibacterial agents.

A novel class of pleuromutilin derivatives possessing 1,2,3-triazole as the linker connected to phenyl analogues were designed. The antibacterial properties of the prepared compounds were assessed in vitro against five strains (E. coli, S. aureus, S. epidermidis, and E. faecalis). Most of the tested compounds displayed potent antibacterial activities against gram-positive bacteria and 14-O-[2-(4-((2,4-dinitrophenoxy)-methyl-1H-1,2,3-triazol-1-yl) acetamide)-2-methylpropan-2-yl) thioacetyl]mutilin (7c) exerted antibacterial activities against S. aureus, MRSA and S. epidermidis with MIC values 0.0625 µg/mL, representing 64-fold, 4-fold and 8-fold higher than tiamulin respectively. Compound 6e, 7c and 8c were chosen to carry out killing kinetics, which exhibited concentration-dependent effect. Subsequently, molecular modeling was conducted to further explore the binding of compound 6e, 7a, 7c, 8c and tiamulin with 50S ribosomal subunit from deinococcus radiodurans. The investigation revealed that the main interactions between compound 7c and the ribosomal residues were three hydrogen bonds, π-π, and p-π conjugate effects. Additionally, the free binding energy and docking score of 7c with the ribosome demonstrated the lowest values of -11.90 kcal/mol and -7.97 kcal/mol, respectively, consistent with its superior antibacterial activities.

Energy metabolism analysis of exogenous glutamate on promoting co-accumulation of astaxanthin yield and biomass in Phaffia rhodozyma D3.

Effective metabolic regulators play an essential role in regulating astaxanthin biosynthesis in Phaffia rhodozyma. In this study, it was found that 5 mM glutamate increased the astaxanthin yield and biomass of P. rhodozyma D3 to 22.34 mg/L and 6.12 g/L, which were 1.22 and 1.33 times higher than the control group, respectively. Meanwhile, glucose uptake was increased and the level of reactive oxygen species (ROS) was reduced with 5 mM glutamate. To further explore the interrelationship between glutamate and astaxanthin synthesis, the energy metabolism of P. rhodozyma D3 with and without glutamate was analysed. Glutamate promoted the Embden-Meyerhof-Parnas pathway (EMP) metabolic flux, modulated the tricarboxylic acid (TCA) cycle and the pentose phosphate pathway (PPP), activated the ornithine cycle and purine metabolism, and provided more ATP and NADPH for astaxanthin accumulation. This study clarified the possible mechanism by which glutamate promoted astaxanthin accumulation in P. rhodozyma.

Transcriptome Analysis of Different Aquaculture Substrates on the Immune Response of Babylonia areolata.

To assess the impact of different substrates in a recirculating water system on the immune response and antioxidant capacity of Babylonia areolata, we conducted a comparative analysis of the transcriptomes and antioxidant performance of the digestive glands in three substrate environments (sand-S group, ceramic granules-C group, and PVC breeding nest-P group). Transcriptome results revealed that the S group and P group exhibited the highest number of differentially expressed genes (DEGs), with a total of 2218 DEGs, including 928 upregulated and 1290 downregulated DEGs. The C group and P group had 1055 DEGs in common, with 316 upregulated and 739 downregulated DEGs. The C group and S group had the fewest DEGs, with 521 in total, including 303 upregulated and 218 downregulated DEGs. GO enrichment analysis showed that in the S vs P group, terms such as catalytic activity, membrane part, and cellular process were enriched with 287, 262, and 180 DEGs, respectively. In the C vs P group, binding, cellular process, and cell part were enriched with 146, 135, and 127 DEGs, respectively. In the C vs S group, catalytic activity, membrane part, and metabolic process were enriched with 90, 83, and 59 DEGs, respectively. Kegg enrichment analysis revealed significant changes in immune-related pathways in the S vs P group, including lysosome, phagosome, and leukocyte transendothelial migration, with 30, 13, and 10 enriched DEGs, respectively. In the C vs P group, phagosome, drug metabolism-other enzymes, and N-Glycan biosynthesis showed significant changes in immune-related pathways, with 9, 6, and 4 enriched DEGs, respectively. In the C vs S group, lysosome, PPAR signaling pathway, and fatty acid degradation exhibited significant changes in immune-related pathways, with 8, 4, and 3 enriched DEGs, respectively. Regarding antioxidant capacity, the S group showed significantly higher total T-AOC than the other experimental groups, while CAT, SOD, POD, and AKP were lower than in the C and P groups. The ACP level in the Sand group was not significantly different from the P group but significantly lower than the C group. In conclusion, substrate environments significantly influence the immune-related genes and key antioxidant enzyme activities in B. areolata.

Correlation between the dynamic changes of γδT cells, Th17 cells, CD4+CD25+ regulatory T cells in peripheral blood and pharmacological interventions against bleomycin-induced pulmonary fibrosis progression in mice.

The involvement of γδT cells, Th17 cells, and CD4+CD25+ regulatory T cells (Tregs) is crucial in the progression of pulmonary fibrosis (PF), particularly in maintaining immune tolerance and homeostasis. However, the dynamics of these cells in relation to PF progression, especially under pharmacological interventions, remains poorly understood. This study aims to unravel the interplay between the dynamic changes of these cells and the effect of pharmacological agents in a mouse model of PF induced by intratracheal instillation of bleomycin. We analyzed changes in lung histology, lung index, hydroxyproline levels, and the proportions of γδT cells, Th17 cells, and Tregs on the 3rd, 14th, and 28th days following treatment with Neferine, Isoliensinine, Pirfenidone, and Prednisolone. Our results demonstrate that these drugs can partially or dynamically reverse weight loss, decrease lung index and hydroxyproline levels, and ameliorate lung histopathological damage. Additionally, they significantly modulated the abnormal changes in γδT, Th17, and Treg cell proportions. Notably, on day 3, the proportion of γδT cells increased in the Neferine and Prednisolone groups but decreased in the Isoliensinine and Pirfenidone groups, while the proportion of Th17 cells decreased across all treated groups. On day 14, the Neferine group showed an increase in all three cell types, whereas the Pirfenidone group exhibited a decrease. In the Isoliensinine group, γδT and Th17 cells increased, and in the Prednisolone group, only Tregs increased. By day 28, an increase in Th17 cell proportion was observed in all treatment groups, with a decrease in γδT cells noted in the Neferine group. These shifts in cell proportions are consistent with the pathogenesis changes induced by these anti-PF drugs, suggesting a correlation between cellular dynamics and pharmacological interventions in PF progression. Our findings imply potential strategies for assessing the efficacy and timing of anti-PF treatments based on these cellular changes.

Expression profiles and characterization of microRNAs responding to chitin in Arthrobotrys oligospora.

Extracellular proteases, such as chitinases secreted by Arthrobotrys oligospora (A. oligospora), play a crucial role in the process of nematode infection. However, post-transcriptional regulation of gene expression involving microRNAs (miRNAs) in A. oligospora remains scarcely described. Hereto, transcriptome sequencing was carried out to analyze the expression profiles of chitin-responsive miRNAs in A. oligospora. Based on the RNA-seq data, the differential expression of miRNAs (DEmiRNAs) in response to chitin was screened, identified and characterized in A. oligospora. Meanwhile, the potential target genes were predicted by the online tools miRanda and Targetscan, respectively. Furthermore, the interaction of DEmiRNA with it's target gene was validated by a dual-luciferase reporter assay system. Among 85 novel miRNAs identified, 25 miRNAs displayed significant differences in expression in A. oligospora in response to chitin. Gene Ontology (GO) analysis showed that the potential genes targeted by DEmiRNAs were enriched in the biological processes such as bio-degradation, extracellular components and cell cycle. KEGG analysis revealed that the target genes were mainly involved in Hippo, carbon and riboflavin metabolic pathway. Outstandingly, chitinase AOL_s00004g379, which is involved in the hydrolysis metabolic pathway of chitin, was confirmed to be a target gene of differential miR_70. These findings suggest that chitin-responsive miRNAs are involved in the regulation of cell proliferation, predator hyphae growth and chitinase expression through the mechanisms of post-transcriptional regulation, which provides a new perspective to the molecular mechanisms underlying miRNAs-mediated control of gene expression in A. oligospora.

Discovery of a novel flavonol O-methyltransferase possessing sequential 4'- and 7-O-methyltransferase activity from Camptotheca acuminata Decne.

The biosynthetic route for flavonol in Camptotheca acuminata has been recently elucidated from a chemical point of view. However, the genes involved in flavonol methylation remain unclear. It is a critical step for fully uncovering the flavonol metabolism in this ancient plant. In this study, the multi-omics resource of this plant was utilized to perform flavonol O-methyltransferase-oriented mining and screening. Two genes, CaFOMT1 and CaFOMT2 are identified, and their recombinant CaFOMT proteins are purified to homogeneity. CaFOMT1 exhibits strict substrate and catalytic position specificity for quercetin, and selectively methylates only the 4'-OH group. CaFOMT2 possesses sequential O-methyltransferase activity for the 4'-OH and 7-OH of quercetin. These CaFOMT genes are enriched in the leaf and root tissues. The catalytic dyad and critical substrate-binding sites of the CaFOMTs are determined by molecular docking and further verified through site-mutation experiments. PHE181 and MET185 are designated as the critical sites for flavonol substrate selectivity. Genomic environment analysis indicates that CaFOMTs evolved independently and that their ancestral genes are different from that of the known Ca10OMT. This study provides molecular insights into the substrate-binding pockets of two new CaFOMTs responsible for flavonol metabolism in C. acuminata.

Degradation performance and mechanism of microcystins in aquaculture water using low-temperature plasma technology.

The eutrophication of aquaculture water bodies seriously restricts the healthy development of the aquaculture industry. Among them, microcystins are particularly harmful. Therefore, the development of technologies for degrading microcystins is of great significance for maintaining the healthy development of the aquaculture industry. The feasibility and mechanism of removing microcystins-LR by dielectric barrier discharge (DBD) plasma were studied. DBD discharge power of 49.6 W and a treatment time of 40 min were selected as the more suitable DBD parameters, resulting in microcystin-LR removal efficiency of 90.4%. Meanwhile, the effects of initial microcystin-LR concentration, initial pH value, turbidity, anions on the degradation effect of microcystin-LR were investigated. The removal efficiency of microcystin-LR decreased with the increase of initial microcystin-LR concentration and turbidity. The degradation efficiency of microcystin-LR at pH 4.5 and 6.5 is significantly higher than that at pH 8.5 and 3.5. HCO3- can inhibit the removal efficiency of microcystin-LR. Furthermore, five intermediates products (m/z = 1029.5, 835.3, 829.3, 815.4, 642.1) were identified in this study, and the toxicity analysis of these degradation intermediates indicated that DBD treatment can reduce the toxicity of microcystin-LR. e－aq, •OH, H2O2, and O3 have been shown to play a major role in the degradation of microcystin-LR, and the contribution ranking of these active species is e－aq > â€¢OH > H2O2 > O3. The application of DBD plasma technology in microcystin-LR removal and detoxification has certain development potential.

Daily impact of the simultaneous passage of binary typhoons on sea surface chlorophyll-a concentration dynamics in the Northwestern Pacific.

Typhoons are recognized as one of the most destructive meteorological phenomena, exerting significant influences on marine ecosystems. Sea surface chlorophyll-a concentration (CHL)an essential indicator of phytoplankton biomass, can be utilized to characterize the disturbances of typhoons on the marine ecosystem. However, it is challenging to investigate this impact at a daily scale due to the missing CHL remote sensing data caused by cloud cover. Given that concurrent passing typhoons may interact with CHL, this study analyzes the effect of the simultaneous passage of binary typhoons Tembin and Bolaven on CHL by using daily CHL reconstruction data, and investigates the role of ocean environmental factors in driving the dynamics of CHL, including sea surface temperature (SST), mixed layer depth (MLD), and sea surface height anomaly (SSHA). The results show that typhoons Tembin and Bolaven increase CHL with the maximum increment of ∼3.2 mg∙m-3 during 4-6 days after typhoons passage. The maximum change areas of CHL are distributed near the intersection of typhoon track of (32°N, 125.2°E), corresponding to the regions of greater variation in SST and MLD. During 15 days before and after typhoons (i.e., from 15 August to 15 September 2012), SST is negatively correlated with CHL (the correlation coefficient of -0.85) and MLD is positively correlated with CHL (the correlation coefficient of -0.80). SST immediately declines after typhoons with a maximum cooling of 7.8 deg. C, showing the decreased SST from ∼28 deg. C to ∼23 deg. C can promote phytoplankton growth. MLD deepens from 10 m to >25 m caused by typhoon-induced strong winds, allowing more nutrients to be transported from the subsurface layer to the euphotic layer for phytoplankton blooms. Furthermore, oceanic eddies captured by SSHA change from cyclonic to anticyclonic eddies accompanied by the beginning of CHL increases, and the largest CHL increases correspond to the distribution of pre-existing cyclonic eddies. It suggests that Tembin and Boravin promote phytoplankton growth to increase CHL by enhancing vertical mixing and upwelling to transport nutrients to the sea surface. These findings inspire us to rethink the daily effects of typhoons on CHL, with critical importance for predicting and managing the ecological consequences of typhoons in the ocean.

Feasibility and mechanism of removing Microcystis aeruginosa and degrading microcystin-LR by dielectric barrier discharge plasma.

Harmful cyanobacterial bloom is one of the serious environmental problems worldwide. Microcystis aeruginosa is a representative harmful alga in cyanobacteria bloom. It is of great significance to develop new technologies for the removal of Microcystis aeruginosa and microcystins. The feasibility and mechanism of removing microcystis aeruginosa and degrading microcystins by dielectric barrier discharge (DBD) plasma were studied. The suitable DBD parameters obtained in this study are DBD (41.5 W, 40 min) and DBD (41.5 W, 50 min), resulting in algae removal efficiency of 77.4% and 80.4%, respectively; scanning electron microscope and LIVE-DEATH analysis demonstrate that DBD treatment can disrupt cell structure and lead to cell death; analysis of elemental composition and chemical state indicated that there are traces of oxidation of organic nitrogen and organic carbon in microcystis aeruginosa; further intracellular ROS concentration and antioxidant enzyme activity analysis confirm that DBD damage microcystis aeruginosa through oxidation. Meanwhile, DBD can effectively degrade the microcystin-LR released after cell lysis, the extracellular microcystin-LR concentration in the DBD (41.5 W) group decreased by 88.7% at 60 min compared to the highest concentration at 20 min; further toxicity analysis of degradation intermediates indicated that DBD can reduce the toxicity of microcystin-LR. The contribution of active substances to the inactivation of microcystis aeruginosa is eaq- > •OH > H2O2 > O3 > 1O2 > •O2- > ONOO-, while on the degradation of microcystin-LR is eaq- > •OH > H2O2 > O3 > •O2- > 1O2 > ONOO-. The application of DBD plasma technology in microcystis aeruginosa algae removal and detoxification has certain prospects for promotion and application.

Changed brain entropy and functional connectivity patterns induced by electroconvulsive therapy in majoy depression disorder.

OBJECTIVE: Our objective is to innovatively integrate both linear and nonlinear characteristics of brain signals in Electroconvulsive Therapy (ECT) research, with the goal of uncovering deeper insights into the pathogenesis of Major Depressive Disorder (MDD) and identifying novel targets for other physical intervention therapies. METHODS: We measured brain entropy (BEN) in 42 MDD patients and 42 matched healthy controls (HC) using rs-fMRI data. Brain regions that differed significantly in patients with MDD before and after ECT were extracted. Then, we use these brain regions as seed points to investigate the differences in whole-brain resting-state functional connectivity (RSFC) patterns before and after ECT. RESULTS: Compared to HCs, patients had higher BEN levels in the right precuneus (PCUN.R) and right angular gyrus (ANG.R). After ECT, patients had lower BEN levels in the PCUN.R and ANG.R. Compared with before ECT, patients showed significantly increased RSFC after ECT between the PCUN.R and right middle temporal gyrus and ANG.R. Significantly increased RSFC was observed between the ANG.R and right middle frontal gyrus and right supramarginal gyrus after ECT. CONCLUSION: Combining the linear and nonlinear characteristics of brain signals can effectively explore the pathogenesis of depression and provide new targets for ECT.

Determination of phosphate in food based on molybdenum yellow derivatization coupled with resonance Rayleigh scattering method.

This paper proposed a rapid, selective and sensitive molybdenum yellow derivatization coupled with Resonance Rayleigh scattering (MYD-RRS) method for detection of phosphate. Under the acidic condition, phosphate can be selectively transformed to Keggin type of phosphomolybdic acid (PMA, i.e., PMo12O403-) through molybdenum yellow derivatization reaction prior to RRS detection. The PMA can further react with cationic methyl violet (MV) to form larger PMA-MV ion association complexes, generating significant RRS signal. The concentration of phosphate was linearly related to the RRS signal in the range of 8-200 ng/mL, with the determining coefficient (R2) of 0.9973 and the detection limit of 4 ng/mL. The analytical procedure can be completed within 10 min and the RRS signal intensity can remain stable more than 4 h. The method showed good stability toward temperature and time, and good anti-interference capability. The method was applied to the determination of phosphate in real food samples with the recovery of 85-117% and RSD of 1-5.2%. With the advantages of rapidness, high sensitivity and good selectivity, the MYD-RRS method exhibits great potential to the determination of phosphate in food. It also provides an instructive strategy for detection of analytes with weak RRS signal.

SMPDL3B is palmitoylated and stabilized by ZDHHC5, and its silencing aggravates diabetic retinopathy of db/db mice: Activation of NLRP3/NF-κB pathway.

Abnormal inflammation of vascular endothelial cells occurs frequently in diabetic retinopathy (DR). Sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B) is a lipid raft enzyme and plays an anti-inflammatory role in various diseases but its function in DR-related vascular endothelial dysfunction remains unknown. We first found that SMPDL3B expression was upregulated from week 10 to 18 in the retinal tissues of db/db mice. Particularly, the high expression of SMPDL3B was mainly observed in retinal vascular endothelium of DR mice. To interfere retinal SMPDL3B expression, adeno-associated viruses 2 (AAV-2) containing SMPDL3B specific shRNA (1233-1253 bp) were injected into the vitreous cavity of db/db mice. SMPDL3B silencing exacerbated the spontaneous DR by further activating the NF-κB/NLRP3 pro-inflammatory pathway. In vitro, human retinal microvascular endothelial cells (HRVECs) were infected with SMPDL3B-shRNA lentiviruses and then stimulated with 30 mM glucose (HG) for 24 h. SMPDL3B-silenced HRVECs secreted more interleukin-1ß and had enhanced nuclear p65 translocation. Notably, HG treatment induced the palmitoylation of SMPDL3B. Zinc finger DHHC-type palmitoyltransferase 5 (ZDHHC5) is a palmitoyltransferase that catalyzes the palmitoylation of its substrates, HG exposure increased the interaction between ZDHHC5 and SMPDL3B in HRVECs. 2-BP, a palmitoylation inhibitor, accelerated the protein degradation of SMPDL3B, whereas palmostatin B, a depalmitoylation inhibitor, decreased its turnover rate in HRVECs. Collectively, the present study suggests a compensatory increase of SMPDL3B in HG-treated HRVECs and the retinal tissues of DR mice, indicating that SMPDL3B may be a potential target for DR treatment.

Monitoring agricultural drought in Peshawar Valley, Pakistan using long -term satellite and meteorological data.

Monitoring agricultural drought across a large area is challenging, especially in regions with limited data availability, like the Peshawar Valley, which holds great agricultural significance in Pakistan. Although remote sensing provides biophysical variables such as precipitation (P), land surface temperature (LST), normalized difference vegetation index (NDVI), and relative soil moisture (RSM) to assess drought conditions at various spatiotemporal scales, these variables have limited capacity to capture the complex nature of agricultural drought and associated crop responses. Here, we developed a composite drought index named "Temperature Vegetation ET Dryness Index" (TVEDI) by modifying the Temperature Vegetation Precipitation Dryness Index (TVPDI) and integrating NDVI, LST, and remotely sensed evapotranspiration (ET) using 3D space and Euclidean distance. Several statistical techniques were employed to examine TVPDI and TVEDI trends and relationships with other commonly used drought indices such as the standardized precipitation index (SPI), standardized precipitation evapotranspiration index (SPEI), and standardized soil moisture index (SSI), as well as crop yield, to better understand how these indices captured the spatial and temporal distribution of agricultural drought in the Peshawar valley between 1986 and 2018. Results indicated that while the temporal patterns of the 3-month SPI, SPEI, and SSI generally align with those of TVEDI and TVPDI, TVEDI was more strongly correlated with these indices (e.g., correlation coefficient, r = 0.78-0.84 from TVEDI and r = 0.73-0.79 from TVPDI). Moreover, the crop yield, a measure of crop response to agricultural drought, demonstrated a significant positive correlation with TVEDI (r = 0.60-0.80), much higher than its correlation with TVPDI (r = 0.30-0.48). These outcomes indicate that the inclusion of ET in TVEDI effectively captured changes in soil moisture, crop water status, and their impact on crop yield. Overall, TVEDI exhibited enhanced capability to identify drought impacts compared to TVPDI, showing its potential for characterizing agricultural drought in regions with limited data availability.

Widefield Diamond Quantum Sensing with Neuromorphic Vision Sensors.

Despite increasing interest in developing ultrasensitive widefield diamond magnetometry for various applications, achieving high temporal resolution and sensitivity simultaneously remains a key challenge. This is largely due to the transfer and processing of massive amounts of data from the frame-based sensor to capture the widefield fluorescence intensity of spin defects in diamonds. In this study, a neuromorphic vision sensor to encode the changes of fluorescence intensity into spikes in the optically detected magnetic resonance (ODMR) measurements is adopted, closely resembling the operation of the human vision system, which leads to highly compressed data volume and reduced latency. It also results in a vast dynamic range, high temporal resolution, and exceptional signal-to-background ratio. After a thorough theoretical evaluation, the experiment with an off-the-shelf event camera demonstrated a 13× improvement in temporal resolution with comparable precision of detecting ODMR resonance frequencies compared with the state-of-the-art highly specialized frame-based approach. It is successfully deploy this technology in monitoring dynamically modulated laser heating of gold nanoparticles coated on a diamond surface, a recognizably difficult task using existing approaches. The current development provides new insights for high-precision and low-latency widefield quantum sensing, with possibilities for integration with emerging memory devices to realize more intelligent quantum sensors.

Assessing size shifts amidst a warming climate in lakes recharged by the Asian Water Tower through satellite imagery.

Recent studies indicate that the Asian Water Tower (AWT) is at risk due to climate change, which can negatively impact water and food security in Asia. However, there is a lack of comprehensive information on lakes' spatial and temporal changes in this region. This information is crucial for understanding the risk magnitude and designing strategies. To fill this research gap, we analyzed 89,480 Landsat images from 1977 ± 2 to 2020 ± 2 to investigate the changes in the size of lakes recharged by the AWT. Our findings showed that out of the 209 lakes larger than 50 km2, 176 (84 %) grew during the wet season and 167 (81 %) during the dry season. 74 % of expanded lakes are located in the Inner Tibetan Plateau (TP) and Tarim basins. The lakes that shrank are found mainly in the Helmand, Indus, and Yangtze basins. Over the entire period, the area of shrinkage (55,077.028 km2 in wet season, 53,986.796 km2 in dry) markedly exceeded expansion (13,000.267 km2 in wet, 11,038.805 km2 in dry), with the drastic decline of the Aral Sea being a major contributor to shrinkage, accounting for 90 % of the total loss. From 1990 ± 2 to 2020 ± 2, alpine lakes mostly expanded, plain lakes mostly shrank, with the opposite trend from 1977 ± 2 to 1990 ± 2. Glacial loss and permafrost thawing under global warming in the Inner TP, Tarim Interior, Syr Darya, and Mekong basins were strongly correlated with lake expansion. However, permafrost discontinuities may prevent significant growth of lakes in the Indus and Ganges basins despite increased recharge. Our findings point to the prominence of the risk the lakes recharged by AWT face. Taking immediate action to manage these risks and adaptation is crucial as the AWT retreats and lake recharges are slowed.

Electroconvulsive therapy enhances degree centrality in the orbitofrontal cortex in depressive rumination.

Depressive rumination has been implicated in the onset, duration, and treatment response of refractory depression. Electroconvulsive therapy (ECT) is remarkably effective in treatment of refractory depression by modulating the functional coordination between brain hubs. However, the mechanisms by which ECT regulates depressive rumination remain unsolved. We investigated degree centrality (DC) in 32 pre- and post-ECT depression patients as well as 38 matched healthy controls. An identified brain region was defined as the seed to calculate functional connectivity (FC) in whole brains. Rumination was measured by the Ruminative Response Scale (RRS) and its relationships with identified DC and FC alterations were examined. We found a significant negative correlation between DC of the right orbitofrontal cortex (rOFC) before ECT and brooding level before and after treatment. Moreover, rOFC DC increased after ECT. DC of the left superior temporal gyrus (lSTG) was positively correlated with reflective level before intervention, while lSTG DC decreased after ECT. Patients showed elevated FC in the rOFC with default mode network. No significant association was found between decreased RRS scores and changes in DC and FC. Our findings suggest that functional changes in rOFC and lSTG may be associated with the beneficial effects of ECT on depressive rumination.

Ameliorating the effect and mechanism of chitosan oligosaccharide on nonalcoholic fatty liver disease in mice.

Previous studies have found that chitosan oligosaccharide (COST) can alleviate the clinical symptoms in non-alcoholic fatty liver disease (NAFLD) patients. We intend to intervene with different concentrations of COST in mice with NAFLD induced by a high fat diet. The basic effect of COST on NAFLD model mice was observed using physiological and biochemical indexes. 16S rRNA sequencing technology was used to analyze the gut microbiota and further analyze the content of short-chain fatty acids (SCFAs). Western blot and RT-PCR were used to detect the effects of COST on the PI3K/AKT/mTOR signaling pathway in the livers of NAFLD mice. It was found that the COST-high-dose group could reduce the weight of NAFLD mice, improve dyslipidemia, and alleviate liver lesions, and COST has a therapeutic effect on NAFLD mice. 16S rRNA sequencing analysis showed that COST could increase the diversity of the gut microbiota in NAFLD mice. The downregulation of SCFAs in NAFLD mice was reversed. WB and RT-PCR results showed that the PI3K/AKT/mTOR signaling pathway was involved in the development of NAFLD mice. COST improved liver lipid metabolism in NAFLD mice by inhibiting liver DNL. COST could increase the expression of thermogenic protein and UCP1 and PGC-1α genes; the PI3K/AKT/mTOR signaling pathway is inhibited at the protein and gene levels. This study revealed that COST regulates the expression of related inflammatory factors caused by lipid toxicity through the gut microbiota and SCFAs, and improves the liver lipid metabolism of HFD-induced NAFLD mice, laying a foundation for the development of effective and low toxicity drugs for the treatment of NAFLD.