Metabolites of traditional Chinese medicine targeting PI3K/AKT signaling pathway for hypoglycemic effect in type 2 diabetes.

Type 2 diabetes mellitus is a chronic metabolic disease characterized by insulin resistance, with high morbidity and mortality worldwide. Due to the tightly intertwined connection between the insulin resistance pathway and the PI3K/AKT signaling pathway, regulating the PI3K/AKT pathway and its associated targets is essential for hypoglycemia and the prevention of type 2 diabetes mellitus. In recent years, metabolites isolated from traditional Chinese medicine has received more attention and acceptance for its superior bioactivity, high safety, and fewer side effects. Meanwhile, numerous in vivo and in vitro studies have revealed that the metabolites present in traditional Chinese medicine possess better bioactivities in regulating the balance of glucose metabolism, ameliorating insulin resistance, and preventing type 2 diabetes mellitus via the PI3K/AKT signaling pathway. In this article, we reviewed the literature related to the metabolites of traditional Chinese medicine improving IR and possessing therapeutic potential for type 2 diabetes mellitus by targeting the PI3K/AKT signaling pathway, focusing on the hypoglycemic mechanism of the metabolites of traditional Chinese medicine in type 2 diabetes mellitus and elaborating on the significant role of the PI3K/AKT signaling pathway in type 2 diabetes mellitus. In order to provide reference for clinical prevention and treatment of type 2 diabetes mellitus.

Nitrogen addition changed soil fungal community structure and increased the biomass of functional fungi in Korean pine plantations in temperate northeast China.

Nitrogen (N) deposition is a global environmental issue that can have significant impacts on the community structure and function in ecosystems. Fungi play a key role in soil biogeochemical cycles and their community structures are tightly linked to the health and productivity of forest ecosystems. Based on high-throughput sequencing and ergosterol extraction, we examined the changes in community structure, composition, and biomass of soil ectomycorrhizal (ECM) and saprophytic (SAP) fungi in 0-10 cm soil layer after 8 years of continuous N addition and their driving factors in a temperate Korean pine plantation in northeast China. Our results showed that N addition increased fungal community richness, with the highest richness and Chao1 index under the low N treatment (LN: 20 kg N ha-1 yr-1). Based on the FUN Guild database, we found that the relative abundance of ECM and SAP fungi increased first and then decreased with increasing N deposition concentration. The molecular ecological network analysis showed that the interaction between ECM and SAP fungi was enhanced by N addition, and the interaction was mainly positive in the ECM fungal network. N addition increased fungal biomass, and the total fungal biomass (TFB) was the highest under the MN treatment (6.05 ± 0.3 mg g-1). Overall, we concluded that N addition changed soil biochemical parameters, increased fungal activity, and enhanced functional fungal interactions in the Korean pine plantation over an 8-year simulated N addition. We need to consider the effects of complex soil conditions on soil fungi and emphasize the importance of regulating soil fungal community structure and biomass for managing forest ecosystems. These findings could deepen our understanding of the effects of increased N deposition on soil fungi in temperate forests in northern China, which can provide the theoretical basis for reducing the effects of increased N deposition on forest soil.

APAF1 Silencing Ameliorates Diabetic Retinopathy by Suppressing Inflammation, Oxidative Stress, and Caspase-3/GSDME-Dependent Pyroptosis.

Objective: Diabetic retinopathy (DR) can cause permanent blindness with unstated pathogenesis. We aim to find novel biomarkers and explore the mechanism of apoptotic protease activating factor 1 (APAF1) in DR. Methods: Differential expression genes (DEGs) were screened based on GSE60436 dataset to find hub genes involved in pyroptosis after comprehensive bioinformatics analysis. DR mice model was constructed by streptozotocin injection. The pathological structure of retina was observed using hematoxylin-eosin staining. The enzyme-linked immunosorbent assay was applied to assess inflammatory factors, vascular endothelial growth factor (VEGF), and oxidative stress. The mRNA and protein expression levels were detected using quantitative real-time polymerase-chain reaction and Western blot. Cell counting kit and flow cytometry were employed to detect proliferation and apoptosis in high glucose-induced ARPE-19 cells. Results: Total 71 pyroptosis-related DEGs were screened. BIRC2, CXCL8, APAF1, PPARG, TP53, and CYCS were identified as hub genes of DR. APAF1 was selected as a potential regulator of DR, which was up-regulated in DR mice. APAF1 silencing alleviated retinopathy and inhibited pyroptosis in DR mice with decreased levels of inflammatory factors, VEGF, and oxidative stress. Moreover, APAF1 silencing promoted proliferation while inhibiting apoptosis and caspase-3/GSDME-dependent pyroptosis with a decrease in TNF-α, IL-1ß, IL-18, and lactate dehydrogenase in high glucose-induced ARPE-19 cells. Additionally, caspase-3 activator reversed the promotion effect on proliferation and inhibitory effect on apoptosis and pyroptosis after APAF1 silencing in high glucose-induced ARPE-19 cells. Conclusion: APAF1 is a novel biomarker for DR and APAF1 silencing inhibits the development of DR by suppressing caspase-3/GSDME-dependent pyroptosis.

Doping Ability Modulated by Interlayer Coupling in AA' and AB Stacked Bilayer V-WS2 Grown with Chemical Vapor Deposition.

Doping in transition metal dichalcogenide (TMD) has received extensive attention for its prospect in the application of photoelectric devices. Currently researchers focus on the doping ability and doping distribution in monolayer TMD and have obtained a series of achievements. Bilayer TMD has more excellent properties compared with monolayer TMD. Moreover, bilayer TMD with different stacking structures presents varying performance due to the difference in interlayer coupling. Herein, this work focuses on doping ability of dopants in different bilayer stacking structures that has not been studied yet. Results of this work show that the doping ability of V atoms in bilayer AA' and AB stacked WS2 is different, and the doping concentration of V atoms in AB stacked WS2 is higher than in AA' stacked WS2 . Moreover, dopants from top and bottom layer can be distinguished by scanning transmission electron microscopy (STEM) image. Density functional theory (DFT) calculation further confirms the doping rule. This study reveals the mechanism of the different doping ability caused by stacking structures in bilayer TMD and lays a foundation for further preparation of controllable-doping bilayer TMD materials.

Distribution of gasification products and emission of heavy metals and dioxins from municipal solid waste at the low temperature pyrolysis stage.

Gasification is widely regarded as one of the most practical, economical, and environmentally friendly waste disposal technologies for municipal solid waste (MSW). The pyrolysis stage (300-500 °C) is crucial for weight loss during MSW gasification, as a considerable amount of organic matter breaks down, producing high-value synthesis gas. This study investigated the product distribution and pollutant emission characteristics within this temperature range and its influencing factors during MSW gasification using a self-designed MSW gasification device. Results indicated that MSW underwent approximately 70% weight loss within this temperature range, yielding low amounts of inorganic and short-chain organic products, with mainly long-chain organic compounds of C16-C34. The atmosphere variation had minimal effect on the elemental composition and content of solid phase products. X-ray fluorescence spectrometry (XRF) and inductively coupled plasma mass spectrometry (ICP-MS) analyses showed that Mn and Zn were the primary components of heavy metal leaching toxicity in solid phase products, with their contents increasing as temperature increased. Synthesis gas showed the highest content of heavy metal As element, reaching a peak at 400 °C. Higher gasification temperature and lower oxygen flow rate significantly reduced the dioxin content and I-TEQ values, with highly chlorinated isomers being the predominant dioxin isomers. Nonetheless, low-chlorinated dioxins accounted for more than 50% of the I-TEQ. This study improves our understanding of the gasification process of MSW.

CMAUP database update 2024: extended functional and association information of useful plants for biomedical research.

Knowledge of the collective activities of individual plants together with the derived clinical effects and targeted disease associations is useful for plant-based biomedical research. To provide the information in complement to the established databases, we introduced a major update of CMAUP database, previously featured in NAR. This update includes (i) human transcriptomic changes overlapping with 1152 targets of 5765 individual plants, covering 74 diseases from 20 027 patient samples; (ii) clinical information for 185 individual plants in 691 clinical trials; (iii) drug development information for 4694 drug-producing plants with metabolites developed into approved or clinical trial drugs; (iv) plant and human disease associations (428 737 associations by target, 220 935 reversion of transcriptomic changes, 764 and 154121 associations by clinical trials of individual plants and plant ingredients); (v) the location of individual plants in the phylogenetic tree for navigating taxonomic neighbors, (vi) DNA barcodes of 3949 plants, (vii) predicted human oral bioavailability of plant ingredients by the established SwissADME and HobPre algorithm, (viii) 21-107% increase of CMAUP data over the previous version to cover 60 222 chemical ingredients, 7865 plants, 758 targets, 1399 diseases, 238 KEGG human pathways, 3013 gene ontologies and 1203 disease ontologies. CMAUP update version is freely accessible at https://bidd.group/CMAUP/index.html.

PM2.5 concentration prediction using weighted CEEMDAN and improved LSTM neural network.

As the core of pollution prevention and management, accurate PM2.5 concentration prediction is crucial for human survival. However, due to the nonstationarity and nonlinearity of PM2.5 concentration data, the accurate prediction for PM2.5 concentration remains a challenge. In this study, a PM2.5 concentration prediction method using weighted complementary ensemble empirical mode decomposition with adaptive noise (WCEEMDAN) and improved long and short-term memory (ILSTM) neural network is proposed. Firstly, a novel WCEEMDAN method is proposed to correctly identify the non-stationary and non-linear characteristics and divide the PM2.5 sequences into various layers. Through the correlation analysis with PM2.5 data, these sub-layers are given different weights. Secondly, the adaptive mutation particle swarm optimization (AMPSO) algorithm is developed to obtain the main hyperparameters of the long short-term memory network (LSTM) neural network, improving the prediction accuracy of PM2.5 concentration. The optimization convergence speed and accuracy are improved by adjusting the inertia weight and introducing the mutation mechanism to enhance the global optimization ability. Finally, three groups of PM2.5 concentration data are utilized to verify the effectiveness of the proposed model. Compared with other methods, the experimental results demonstrate the superiority of the proposed model. The source code can be downloaded from https://github.com/zhangli190227/WCEENDAM-ILSTM .

Characteristics and properties of a polysaccharide isolated from Wolfiporia cocos as potential dietary supplement for IBS.

Introduction: As low FODMAP (Fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet therapy is recommended for most of Irritable Bowel Syndrome (IBS) patients, the consequent insufficient of dietary fibers (DFs) intake exert an adverse impact on intestinal health. It is necessary to find suitable DFs for IBS patients. Methods: This study extracted a water-insoluble polysaccharide from Wolfiporia cocos (WIP) by alkali-extraction and acid-precipitation method. Its molecular weight was detected by high performance gel permeation chromatography (HPGPC) analysis. The structure of WIP was analyzed by Fourier transform infrared (FT-IR) spectrum, Nuclear Magnetic Resonance (NMR) spectra and X-ray diffraction (XRD). The properties related to stability, digestion, viscosity, osmotic activity, adsorption and fermentation were investigated, aimed to explore the feasibility of WIP as a new DF supplement for patients with IBS. In addition, 16S rRNA sequencing analysis was conducted to explore its effects on IBS-related gut microbiota. Results and Discussion: The results showed that WIP had a single homogeneous composition and the molecular weight was 8.1 × 103 Da. WIP was indicated as a kind of pyranose form with ß anomeric configuration and the main chain of WIP was 1,3-ß-glucan with amorphous structure. In addition to good thermal stability, WIP also has low bioavailability and can reach the colon mostly without being digested. Moreover, the low viscosity and osmotic activity, the high water- swelling and water/oil-holding capacity, fructose adsorption capacity and poor fermentation performance of WIP demonstrated that it is suitable for IBS patients. It is worth noting that WIP regulates IBS associated gut microbiota effectively, such as the abundance of Lachnospiraceae and Prevotella. These findings provide a theoretical basis for the development of WIP as a dietary supplement for IBS patients with low FODMAP diet therapy. GRAPHICAL ABSTRACT.

Arbuscular mycorrhizal fungi influence the uptake of cadmium in industrial hemp (Cannabis sativa L.).

Phytoremediation is currently a more environmentally friendly and economical measure for the remediation of cadmium (Cd) contaminated soil. Heavy metal-resistant plant species, Cannabis sativa L. was inoculated with Rhizophagus irregularis to investigate the mechanisms of mycorrhizal in improving the Cd remediation ability of C. sativa. The results showed that after inoculation with R. irregularis, C. sativa root Cd contents increased significantly, and leaf Cd enrichment decreased significantly. At the transcriptional level, R. irregularis down-regulated the expression of the ABC transporter family but up-regulated differentially expressed genes regulating low molecular weight organic acids. The levels of malic acid, citric acid, and lactic acid were significantly increased in the rhizosphere soil, and they were significantly and strongly related to oxidizable Cd concentrations. Then citric acid levels were considerably and positively connected to exchangeable Cd concentrations. Our findings revealed that through regulating the movement of root molecules, arbuscular mycorrhizal fungus enhanced the heavy metal tolerance of C. sativa even more, meanwhile, they changed the Cd chemical forms by altering the composition of low molecular weight organic acids, which in turn affected soil Cd bioavailability.

Comparative analysis of the vaginal microbiome of healthy and polycystic ovary syndrome women: a large cross-sectional study.

RESEARCH QUESTION: What are the different features of the vaginal microbiome (VMB) between patients with polycystic ovary syndrome (PCOS) and healthy women? DESIGN: A cross-sectional study was conducted at a single academic university-affiliated centre. A total of 1446 participants were recruited (PCOS group, n =713, control group, n = 733). Vaginal swabs were analysed using 16S rRNA gene sequencing. The diversity and composition of the microbiome were compared between the PCOS group and the control group. Microbial interaction networks and functional prediction were investigated. RESULTS: The PCOS group had a higher alpha diversity than the control group (Shannon P = 0.03, Simpson P = 0.02), and higher intra-group variability was observed in PCOS group (P < 2.2E-16). At the genus level, the proportion of Lactobacillus decreased (85.1% versus 89.3%, false discovery rate [FDR] = 0.02), whereas the proportion of Gardnerella vaginalis and Ureaplasma increased in the PCOS group (5.1% versus 3.3%, FDR = 0.006; 1.2% versus 0.6%, FDR = 0.002, respectively). Lactobacillus acidophilus, Prevotella buccalis and G. vaginalis were identified as the main differential species. L. acidophilus was positively correlated with serum levels of anti-Müllerian hormone (AMH), and triglyceride (P = 2.01E-05, P = 0.004, respectively). P. buccalis was negatively correlated with serum levels of AMH and testosterone (P = 0.002, P = 0.003, respectively). G. vaginalis was positively correlated with serum levels of AMH, oestradiol and progesterone (P = 0.004, P = 0.005, P = 0.03, respectively). The VMB interaction network indicated that Lactobacillus crispus, Prevotella timonensis, and P. buccalis could be key drivers in the PCOS group. Overall, 55 predicted genes were found to be differentially abundant between PCOS and the control (FDRs < 0.25). CONCLUSIONS: The PCOS group had a higher diversity of vaginal microbiome and showed an enhanced level of heterogeneity. The proportion of Lactobacillus in the PCOS group decreased, whereas the proportions of Gardnerella and Ureaplasma increased. These results warrant further research that can validate the correlation between PCOS and VMB.

Rhizophagus irregularis enhances tolerance to cadmium stress by altering host plant hemp (Cannabis sativa L.) photosynthetic properties.

Arbuscular mycorrhizal fungi (AMF) are widespread and specialized soil symbiotic fungi, and the establishment of their symbiotic system is of great importance for adversity adaptation. To reveal the growth and photosynthetic characteristics of AMF-crop symbionts in response to heavy metal stress, this experiment investigated the effects of Rhizophagus irregularis (Ri) inoculation on the growth, photosynthetic gas exchange parameters, and chlorophyll fluorescence characteristics of hemp (Cannabis sativa L.) at a Cd concentration of 80 mg/kg. The results showed that (1) under Cd stress, the biomass of each plant structure in the Ri treatment was significantly higher than that in the noninoculation treatment (P < 0.05); (2) under Cd stress, the transpiration rate, stomatal conductance, net photosynthetic rate, PSII efficiency, apparent electron transport rate and photochemical quenching coefficient of the Ri inoculation group reached a maximum, with increases ranging from 1% to 28%; (3) inoculation of Ri significantly reduced Cd enrichment in leaves, which in turn significantly increased the transpiration rate, stomatal conductance, electron transfer rate, net photosynthetic rate and photosynthetic intensity, protecting PSII (P < 0.05); and (4) by measuring the light response curves of different treatments, the light saturation points of hemp inoculated with the Ri treatment reached 1448.4 µmol/m2/s, and the optical compensation point reached 24.0 µmol/m2/s under Cd stress. The Ri-hemp symbiont demonstrated high adaptability to weak light and high utilization efficiency of strong light under Cd stress. Our study showed that Ri-hemp symbiosis improves adaptation to Cd stress and promotes plant growth by regulating the photosynthetic gas exchange parameters and chlorophyll fluorescence parameters of plants. The Ri-hemp symbiosis is a promising technology for improving the productivity of Cd-contaminated soil.

Microstructure Evolution of Graphene and the Corresponding Effect on the Mechanical/Electrical Properties of Graphene/Cu Composite during Rolling Treatment.

Rolling enables the directional alignment of the reinforcements in graphene/Cu composites while achieving uniform graphene dispersion and matrix grain refinement. This is expected to achieve a breakthrough in composite performance. In this paper, the process parameters of rolling are investigated, and the defects, thickness variations of graphene and property changes of the composite under different parameters are analyzed. High-temperature rolling is beneficial to avoid the damage of graphene during rolling, and the prepared composites have higher electrical conductivity. The properties of graphene were investigated. Low-temperature rolling is more favorable to the thinning and dispersion of graphene; meanwhile, the relative density of the composites is higher in the low-temperature rolling process. With the increase of rolling deformation, the graphene defects slightly increased and the number of layers decreased. In this paper, the defect states of graphene and the electrical conductivity with different rolling parameters is comprehensively investigated to provide a reference for the rolling process of graphene/copper composites with different demands.

Study on the Evolution of Graphene Defects and the Mechanical and Thermal Properties of GNPs/Cu during CVD Repair Process.

Graphene has extremely high theoretical strength and electrothermal properties, and its application to Cu-based composites is expected to achieve a breakthrough in the performance of existing composites. As a nano-reinforced body, graphene often needs a long time of ball milling to make it uniformly dispersed, but the ball milling process inevitably brings damage to the graphene, causing the performance of the composite to deviate from expectations. Therefore, this paper uses CH4 as a carbon source to repair graphene through a CVD process to prepare low-damage graphene/Cu composites. The process of graphene defect generation was studied through the ball milling process. The effects of defect content and temperature on the graphene repair process were studied separately. The study found that the graphene defect repair process, the decomposition process of oxygen-containing functional groups, and the deposition process of active C atoms existed simultaneously in the CVD process. When the repair temperature was low, the C atom deposition process and the oxygen-containing functional group decomposition process dominated. In addition, when the repair temperature is high, the graphene defect repair process dominated. 3 wt% graphene/Cu composites were prepared by pressure infiltration, and it was found that the bending strength was increased by 48%, the plasticity was also slightly increased, and the thermal conductivity was increased by 10-40%. This research will help reduce graphene defects, improve the intrinsic properties of graphene, and provide theoretical guidance for the regulation of C defects in composites.

The Salmonella effectors SseF and SseG inhibit Rab1A-mediated autophagy to facilitate intracellular bacterial survival and replication.

In mammalian cells, autophagy plays crucial roles in restricting further spread of invading bacterial pathogens. Previous studies have established that the Salmonella virulence factors SseF and SseG are required for intracellular bacterial survival and replication. However, the underlying mechanism by which these two effectors facilitate bacterial infection remains elusive. Here, we report that SseF and SseG secreted by Salmonella Typhimurium (S. Typhimurium) inhibit autophagy in host cells and thereby establish a replicative niche for the bacteria in the cytosol. Mechanistically, SseF and SseG impaired autophagy initiation by directly interacting with the small GTPase Rab1A in the host cell. This interaction abolished Rab1A activation by disrupting the interaction with its guanine nucleotide exchange factor (GEF), the TRAPPIII (transport protein particle III) complex. This disruption of Rab1A signaling blocked the recruitment and activation of Unc-51-like autophagy-activating kinase 1 (ULK1) and decreased phosphatidylinositol 3-phosphate biogenesis, which ultimately impeded autophagosome formation. Furthermore, SseF- or SseG-deficient bacterial strains exhibited reduced survival and growth in both mammalian cell lines and mouse infection models, and Rab1A depletion could rescue these defects. These results reveal that virulence factor-dependent inactivation of the small GTPase Rab1A represents a previously unrecognized strategy of S Typhimurium to evade autophagy and the host defense system.