Extract of Tinospora sinensis alleviates LPS-induced neuroinflammation in mice by regulating TLR4/NF-κB/NLRP3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried rattan stem of Tinospora sinensis (Lour.) Merr. is valued for its efficacy of clearing heat and removing toxicity, calming and soothing the nerves. It is widely used in Tibetan medicine for the treatment of rheumatic and aging diseases. Studies have confirmed its anti-inflammatory and ameliorating effects on Alzheimer's disease; however, the anti-neuroinflammation efficacy and mechanism remain unclear. AIM: This study aimed to explore the anti-neuroinflammation efficacy, major effective ingredients, and potential mechanism of extract of Tinosporae sinenisis (TIS). METHODS: UPLC-Q-TOF/MS was used to identify the compounds of TIS and the plasma components of rats after gastric administration of TIS. C57BL/6J mice were continuously intraperitoneally injected with lipopolysaccharide (LPS) (250 µg/kg) for 14 d to establish a neuroinflammation model. The effects of TIS (4.5 g/kg, 9 g/kg) on the learning and memory abilities in mice with neuroinflammation was evaluated using spontaneous activity, novel object recognition, and Morris water maze tests. Pathological changes in the hippocampus were observed using hematoxylin and eosin staining. Gene and protein levels of inflammatory factors in the brain were detected using qRT-PCR and ELISA kits. Iba-1 levels in the brain were detected using immunofluorescence to assess the degree of microglial activation. Network pharmacology, based on the components absorbed into plasma of TIS, was used to predict potential targets and pathways. Proteomics was used to study the differentially expressed proteins and related pathways in the brain tissue of mice with neuroinflammation. Finally, correlation analysis was performed on the results of network pharmacology and proteomics, and proteins related the anti-neuroinflammatory effect of TIS were detected by western blot. RESULTS: A total of 39 compounds were identified in TIS: genipingentiobioside, isocorydin, reticuline, (-)-argemonine, tinosineside A, tinosinenside A, and costunolide were absorbed into the plasma. After continuous intraperitoneal injection of LPS into C57BL/6J mice, microglia in the brain tissue were activated and the gene and protein levels of IL-1ß, TNF-α, IL-6, and iNOS were increased in the brain tissue, suggesting that the neuroinflammation model was successfully established. TIS reduced Iba-1 levels and gene expression and protein levels of inflammatory factors in the brain of mice with neuroinflammation. Furthermore, TIS improved the pathological changes in the hippocampus and learning and memory abilities caused by neuroinflammation. Network pharmacology has predicted that TNF, IL-1ß, and IκBKB are closely related to neuroinflammation. Proteomics identified key differentially expressed proteins, including TNF, NF-κB2, NF-κBIA, and TLR4. Toll-like receptor (TLR), NF-κB, and NOD-like receptor (NLR) signaling pathways are involved in neuroinflammation-related pathways. Correlation analysis revealed TLR, TNF and NLR signaling pathways were closely related to the anti-neuroinflammatory effects of TIS. We observed that TIS alleviated neuroinflammation by inhibiting the TLR4/NF-κB/NLRP3 pathway. CONCLUSION: Thirty-nine compounds were identified from TIS, among which seven were absorbed into the plasma as prototype components. TIS alleviated LPS-induced neuroinflammation in mice, and its mechanism was related to inhibition of TLR4/NF-κB/NLRP3 signaling pathway.

Combining the Optimized Maximum Entropy Model to Detect Key Factors in the Occurrence of Oedaleus decorus asiaticus in the Typical Grasslands of Central and Eastern Inner Mongolia.

Grasshoppers pose a significant threat to both natural grassland vegetation and crops. Therefore, comprehending the relationship between environmental factors and grasshopper occurrence is of paramount importance. This study integrated machine learning models (Maxent) using the kuenm package to screen MaxEnt models for grasshopper species selection, while simultaneously fitting remote sensing data of major grasshopper breeding areas in Inner Mongolia, China. It investigated the spatial distribution and key factors influencing the occurrence of typical grasshopper species in grassland ecosystems. The modelling results indicate that a typical steppe has a larger suitable area. The soil type, above biomass, altitude, and temperature, predominantly determine the grasshopper occurrence in typical steppes. This study explicitly delineates the disparate impacts of key environmental factors (meteorology, vegetation, soil, and topography) on grasshopper occurrence in typical steppes. Furthermore, it provides a methodology to guide early warning and precautions for grasshopper pest prevention. The findings of this study will be instrumental in formulating future management measures to guarantee grass ecological environment security and the sustainable development of grassland.

Functional metabolomics characterizes the contribution of farnesoid X receptor in pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome.

Consumption of herbal products containing pyrrolizidine alkaloids (PAs) is one of the major causes for hepatic sinusoidal obstruction syndrome (HSOS), a deadly liver disease. However, the crucial metabolic variation and biomarkers which can reflect these changes remain amphibious and thus to result in a lack of effective prevention, diagnosis and treatments against this disease. The aim of the study was to determine the impact of HSOS caused by PA exposure, and to translate metabolomics-derived biomarkers to the mechanism. In present study, cholic acid species (namely, cholic acid, taurine conjugated-cholic acid, and glycine conjugated-cholic acid) were identified as the candidate biomarkers (area under the ROC curve 0.968 [95% CI 0.908-0.994], sensitivity 83.87%, specificity 96.55%) for PA-HSOS using two independent cohorts of patients with PA-HSOS. The increased primary bile acid biosynthesis and decreased liver expression of farnesoid X receptor (FXR, which is known to inhibit bile acid biosynthesis in hepatocytes) were highlighted in PA-HSOS patients. Furtherly, a murine PA-HSOS model induced by senecionine (50 mg/kg, p.o.), a hepatotoxic PA, showed increased biosynthesis of cholic acid species via inhibition of hepatic FXR-SHP singling and treatment with the FXR agonist obeticholic acid restored the cholic acid species to the normal levels and protected mice from senecionine-induced HSOS. This work elucidates that increased levels of cholic acid species can serve as diagnostic biomarkers in PA-HSOS and targeting FXR may represent a therapeutic strategy for treating PA-HSOS in clinics.

Study on the prediction method of grasshopper occurrence risk in Inner Mongolia based on the maximum entropy model during the growing period.

Grasshoppers represent a significant biological challenge in Inner Mongolia's grasslands, severely affecting the region's animal husbandry. Thus, dynamic monitoring of grasshopper infestation risk is crucial for sustainable livestock farming. This study employed the Maxent model, along with remote sensing data, to forecast Oedaleus decorus asiaticus occurrence during the growing season, using grasshopper suitability habitats as a base. The Maxent model's predictive accuracy was high, with an AUC of 0.966. The most influential environmental variables for grasshopper distribution were suitable habitat data (34.27%), the temperature-vegetation dryness index during the spawning period (18.81%), and various other meteorological and vegetation factors. The risk index model was applied to calculate the grasshopper distribution across different risk levels for the years 2019-2022. The data indicated that the level 1 risk area primarily spans central, eastern, and southwestern Inner Mongolia. By examining the variable weights, the primary drivers of risk level fluctuation from 2019 to 2022 were identified as accumulated precipitation and land surface temperature anomalies during the overwintering period. This study offers valuable insights for future O. decorus asiaticus monitoring in Inner Mongolia.

Analysis of Spatiotemporal Variation in Habitat Suitability for Oedaleus decorus asiaticus Bei-Bienko on the Mongolian Plateau Using Maxent and Multi-Source Remote Sensing Data.

O. decorus asiaticus is a major grasshopper species that harms the development of agriculture on the Mongolian Plateau. Therefore, it is important to enhance the monitoring of O. decorus asiaticus. In this study, the spatiotemporal variation in the habitat suitability for O. decorus asiaticus on the Mongolian Plateau was assessed using maximum entropy (Maxent) modeling along with multi-source remote sensing data (meteorology, vegetation, soil, and topography). The predictions of the Maxent model were accurate (AUC = 0.910). The key environmental variables affecting the distribution of grasshoppers and their contribution were grass type (51.3%), accumulated precipitation (24.9%), altitude (13.0%), vegetation coverage (6.6%), and land surface temperature (4.2%). Based on the assessment results of suitability by Maxent model, the model threshold settings, and the formula for calculating the inhabitability index, the 2000s, 2010s, and 2020s inhabitable areas were calculated. The results show that the distribution of suitable habitat for O. decorus asiaticus in 2000 was similar to that in 2010. From 2010 to 2020, the suitability of the habitat for O. decorus asiaticus in the central region of the Mongolian Plateau changed from moderate to high. The main factor contributing to this change was accumulated precipitation. Few changes in the areas of the habitat with low suitability were observed across the study period. The results of this study enhance our understanding of the vulnerability of different regions on the Mongolian Plateau to plagues of O. decorus asiaticus and will aid the monitoring of grasshopper plagues in this region.

Syringin inhibits endogenous volume regulated anion channel currents of HEK293 cells in hypotonic circumstances.

Syringin is a natural chemical compound first isolated from the bark of lilac and is known to have neuroprotective effects in middle cerebral artery occlusion (MCAO). Volume regulated anion channel (VRAC) is a cell swelling-activated anion channel, which is implicated in brain ischemia. However, the mechanism underlying the syringin protecting the neuron from damage in MCAO is still unclear. We hypothesized that syringin has an inhibitory effect on the opening of VRAC channels. To access the effect of syringin on VRAC currents and predict how syringin interacts with VRAC proteins, we performed whole-cell patch-clamp experiments using HEK293 cells. Initially, HEK293 cells were perfused with isotonic extracellular solution, followed by hypotonic extracellular solution to stimulate endogenous VRAC currents. Once the VRAC currents reached a steady state, the hypotonic solution containing syringin was perfused to study the effect of syringin on VRAC currents. The potential interaction between syringin and the VRAC protein was investigated using molecular docking as a predictive model. In this study, we found that syringin moderately inhibited VRAC currents in a dose-dependent manner. The potential binding of syringin to LRRC8 protein was predicted through in silico molecular docking, which suggests an affinity of -6.6 kcal/mol and potential binding sites of arginine 103 and leucine 101. Our results herein characterize syringin as an inhibitor of the VRAC channels, which provides valuable insights for the future development of VRAC channel inhibitors.

[Effect of Erjing Pills on alleviating neuroinflammation of AD rats based on TLR4/NF-κB/NLRP3 pathway and its mechanism].

This paper aimed to study the effect of Erjing Pills on the improvement of neuroinflammation of rats with Alzheimer's di-sease(AD) induced by the combination of D-galactose and Aß_(25-35) and its mechanism. SD rats were randomly divided into a sham group, a model control group, a positive drug group(donepezil, 1 mg·kg~(-1)), an Erjing Pills high-dose group(9.0 g·kg~(-1)), and an Erjing Pills low-dose group(4.5 g·kg~(-1)), with 14 rats each group. To establish the rat model of AD, Erjing Pills were intragastrically administrated to rats for 5 weeks after 2 weeks of D-galactose injection. D-galactose was intraperitoneally injected into rats for 3 weeks, and then Aß_(25-35) was injected into the bilateral hippocampus. The new object recognition test was used to evaluate the learning and memory ability of rats after 4 weeks of intragastric administration. Tissues were acquired 24 h after the last administration. The immunofluorescence method was used to detect the activation of microglia in the brain tissue of rats. The positive expressions of Aß_(1-42) and phosphory protein Tau~(404)(p-Tau~(404)) in the CA1 area of the hippocampus were detected by immunohistochemistry. The levels of inflammatory factors interleukin-1ß(IL-1ß), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) in the brain tissue were determined by enzyme-linked immunosorbent assay(ELISA). Toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)/nucleotide-binding oligomerization domain-like receptors 3(NLRP3) pathway-associated proteins in the brain tissue were determined by Western blot. The results showed that as compared with the sham group, the new object recognition index of rats in the model control group decreased significantly, the deposition of Aß_(1-42) and p-Tau~(404) positive protein in the hippocampus increased significantly, and the levels of microglia activation increased significantly in the dentate gyrus. The levels of IL-1ß, TNF-α, and IL-6 in the hippocampus of the model control group increased significantly, and the expression levels of TLR4, p-NF-κB p65/NF-κB p65, p-IκBα/IκBα, and NLRP3 proteins in the hippocampus increased significantly. Compared with the model control group, the Erjing Pill groups enhanced the new object recognition index of rats, decreased the deposition of Aß_(1-42) and the expression of p-Tau~(404) positive protein in the hippocampus, inhibited the activation of microglia in the dentate gyrus, reduced the levels of inflammatory factors IL-1ß, TNF-α, and IL-6 in the hippocampus, and down-regulated the expression levels of TLR4, p-NF-κB P65/NF-κB P65, p-IκBα/IκBα, and NLRP3 proteins in the hippocampus. In conclusion, Erjing Pills can improve the learning and memory ability of the rat model of AD presumably by improving the activation of microglia, reducing the expression levels of neuroinflammatory factors IL-1ß, TNF-α, and IL-6, inhibiting the TLR4/NF-κB/NLRP3 neuroinflammation pathway, and decreasing hippocampal deposition of Aß and expression of p-Tau, thereby restoring the hippocampal morphological structure.

Assessment on Potential Suitable Habitats of the Grasshopper Oedaleus decorus asiaticus in North China based on MaxEnt Modeling and Remote Sensing Data.

Grasshopper populations can quickly grow to catastrophic levels, causing a huge amount of damage in a short time. Oedaleus decorus asiaticus (Bey-Bienko) (O. d. asiaticus) is the most serious species in Xilingol League of the Inner Mongolia Autonomous Region. The region is not only an important grassland but also a site of agricultural heritage systems in China. Therefore, projecting the potential geographic distribution of O. d. asiaticus to provide an early warning is vital. Here, we combined temperature, precipitation, soil, vegetation, and topography with remote sensing data to screen the predictors that best characterize the current geographical distribution of O. d. asiaticus. A MaxEnt model approach was applied to project the potential suitable distribution of O. d. asiaticus in Xilingol League (the Inner Mongolia Autonomous Region of China) combined with a set of optimized parameters. The modeling results indicated that there were six main habitat factors that determined the suitable distribution of O. d. asiaticus such as the soil type (ST), grassland type (GT), elevation, precipitation during the growing period (GP), precipitation during the spawning period (SP), and normalized difference vegetation index during the overwintering period (ONDVI). The simulated result was good, with average AUC and TSS values of 0.875 and 0.812, respectively. The potential inhabitable areas of grasshoppers were 198,527 km2, distributed mainly in West Urumqi, Xilinhot City, East Urumqi, Abaga Banner, and Xianghuang Banner of Xilingol League. This study is valuable to guide managers and decision-makers to prevent and control the occurrence of O. d. asiaticus early on and this study may facilitate meaningful reductions in pesticide application.

Research on the Material Basis and Mechanism of Kudzu Root in Preventing and Treating Cerebral Ischemia based on Network Pharmacology.

BACKGROUND: It has been shown that Kudzu root has significant pharmacological effects such as improving microcirculation, dilating coronary arteries, and increasing cerebral and coronary blood flow, but its material basis and mechanism of action are not clear. OBJECTIVE: The aim of this study was to investigate the mechanism of action of Kudzu root in the prevention and treatment of cerebral ischemia (CI) through network pharmacology combined with animal experiments. METHODS: The components of kudzu root were screened by using the Chemistry Database, Chinese Academy of Science. Linpinski's five rules were used to perform pharmacophore-like analysis to obtain the active ingredients of Kudzu root. The Swiss Target Prediction Service database was used to predict the potential protein targets of kudzu root components associated with CI. An active ingredient-target network was constructed by using Cytoscape 3.6.0. A rat model of middle cerebral artery occlusion (MCAO) was established, then the main targets and signaling pathways predicted were verified by observing the area of cerebral infarction and Western blot experiments. RESULTS: In total, 84 major active compounds and 34 targets included gerberoside, belonging to the isoflavone class, gallic acid, amino acid class, 4-Methylphenol, phenolic class, and quercetin, and flavonoid class (Flavonoids). The targets covered were proteins related to excitatory amino acids and calcium overload, including Excitatory amino acid transporter 2 (SLC1A2), Glutamate receptor ionotropic, kainate 1 (GRIK1), Glutamate receptor ionotropic, NMDA 1 (GRIN1), Glutamate receptor 2(GRIA2), Calcium/calmodulin-dependent protein kinase II (CaMKII), Neuronal nitric oxide synthase(nNOS). Glutamatergic energy is prominent, and calcium transport across the membrane is central to the network and occupies an important position. CONCLUSION: Kudzu root can significantly reduce neurological damage in rats with CI, and also significantly reduce the rate of cerebral infarction. It is worth noting that Kudzu root can prevent and treat CI by reducing excitatory amino acid toxicity and improving calcium overload.

Exploring the mechanism of the antithrombotic effects of Pueraria lobata and Pueraria lobata var. thomsonii based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Pueraria lobata (Willd.) Ohwi and Pueraria lobata var. thomsonii (Benth.) Maesen are nutritious medicine food homology plants that are widely used in the food and health products industry and are excellent natural materials for the development of new health foods, with great potential for domestic and foreign markets. Clinically, P. lobata and P. thomsonii are used to treat coronary heart disease, atherosclerosis, cerebral infarction and other cardiovascular diseases, and antithrombotic actions may be their core effect in the treatment of thrombotic diseases. However, the underlying mechanisms of the antithrombotic properties of P. lobata and P. thomsonii have not been clarified. METHODS: First, P. lobata and P. thomsonii were identified by high-performance liquid chromatography (HPLC). An arteriovenous bypass thrombosis rat model was established. Thrombus dry‒wet weight, platelet accumulation rate and the four coagulation indices, including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and fibrinogen (FIB), were detected in plasma to manifest the P. lobata and P. thomsonii antithrombotic function. Network pharmacology and molecular docking methods were used to obtain key targets and verify reliability. David 6.8 was used for GO and KEGG analyses to explore pathways and potential targets for P. lobata and P. thomsonii antithrombotic functions. Prostaglandin I2 (PGI2), thromboxane A2 (TXA2), cyclooxygenase 2 (COX-2), myeloperoxidase (MPO) and endothelial nitric oxide synthase (eNOS) were tested by enzyme-linked immunosorbent assay (ELISA). RESULTS: The results indicated that P. lobata and P. thomsonii can reduce thrombus dry‒wet weight and platelet accumulation in rats and inhibit TT, APTT, FIB, and PT. A comprehensive network pharmacology approach successfully identified 9 active ingredients in P. lobata and P. thomsonii. The main active ingredients include polyphenols, amino acids and flavonoids. A total of 15 antithrombotic function targets were obtained, including 3 key targets (PTGS2, NOS3, MPO). Pathway analysis showed 10 significant related pathways and 29 biological processes. P. lobata and P. thomsonii inhibited platelet aggregation by upregulating PGI2 and downregulating TXA2, inhibited PTGS2 to reduce inflammation, and increased the level of eNOS to promote vasodilation. In addition, P. lobata and P. thomsonii alleviated oxidative stress by increasing SOD levels and significantly decreasing MDA contents. CONCLUSION: The results of the study further clarify the antithrombotic mechanism of action of P. lobata and P. thomsonii, which provides a scientific basis for the development of new drugs for thrombogenic diseases and lays the foundation for the development of P. lobata and P. thomsonii herbal resources and P. lobata and P. thomsonii health products.

Detecting Key Factors of Grasshopper Occurrence in Typical Steppe and Meadow Steppe by Integrating Machine Learning Model and Remote Sensing Data.

Grasshoppers mainly threaten natural grassland vegetation and crops. Therefore, it is of great significance to understand the relationship between environmental factors and grasshopper occurrence. This paper studies the spatial distribution and key factors of grasshopper occurrence in two grass types by integrating a machine learning model (Maxent) and remote sensing data within the major grasshopper occurrence areas of Inner Mongolia, China. The modelling results demonstrate that the typical steppe has larger suitable area and more proportion for grasshopper living than meadow steppe. The soil type, above biomass, altitude and temperature mainly determine the grasshopper occurrence in typical steppe and meadow steppe. However, the contribution of these factors in the two grass types is significantly different. In addition, related vegetation and meteorological factors affect the different growing stages of grasshoppers between the two grass types. This study clearly defines the different effects of key environmental factors (meteorology, vegetation, soil and topography) for grasshopper occurrence in typical steppe and meadow steppe. It also provides a methodology to guide early warning and precautions for grasshopper pest prevention. The findings of this study will be helpful for future management measures, to ensure grass ecological environment security and the sustainable development of grassland.

Optical meta-waveguides for integrated photonics and beyond.

The growing maturity of nanofabrication has ushered massive sophisticated optical structures available on a photonic chip. The integration of subwavelength-structured metasurfaces and metamaterials on the canonical building block of optical waveguides is gradually reshaping the landscape of photonic integrated circuits, giving rise to numerous meta-waveguides with unprecedented strength in controlling guided electromagnetic waves. Here, we review recent advances in meta-structured waveguides that synergize various functional subwavelength photonic architectures with diverse waveguide platforms, such as dielectric or plasmonic waveguides and optical fibers. Foundational results and representative applications are comprehensively summarized. Brief physical models with explicit design tutorials, either physical intuition-based design methods or computer algorithms-based inverse designs, are cataloged as well. We highlight how meta-optics can infuse new degrees of freedom to waveguide-based devices and systems, by enhancing light-matter interaction strength to drastically boost device performance, or offering a versatile designer media for manipulating light in nanoscale to enable novel functionalities. We further discuss current challenges and outline emerging opportunities of this vibrant field for various applications in photonic integrated circuits, biomedical sensing, artificial intelligence and beyond.

Subwavelength adiabatic multimode Y-junctions.

Adiabatic multimode Y-junctions are extensively used for the design of multimode silicon photonics devices due to their straightforward principle in achieving mode splitting and manipulation. However, experimentally, the limited feature size achievable by lithography can greatly deteriorate the adiabatic branching property and result in large excess loss and crosstalk. Here, we propose a branch structure consisting of a circular-hole-based chirped subwavelength slot. By optimizing the holes' radii and positions under our fabrication constraint, we designed and experimentally demonstrated both symmetric and asymmetric approximately adiabatic four-mode Y-junctions with excellent performance close to ideal Y-junctions over a broad wavelength span. Such junctions are compact, CMOS-compatible, exhibit a relatively large fabrication tolerance, and could be extended for more modes; hence they can be potentially deployed for mode-division multiplexing silicon-photonic systems.

Inverse design and demonstration of an ultracompact broadband dual-mode 3 dB power splitter.

An ultracompact broadband dual-mode 3 dB power splitter using inverse design method for highly integrated on-chip mode (de) multiplexing system is proposed and experimentally demonstrated. A dual-mode convertor based on subwavelength axisymmetric three-branch waveguide is utilized to convert TE0 and TE1 to three intermediate fundamental modes. The axisymmetric topology constraint of the nanostructures enables the optimized device to achieve a strict 50:50 splitting ratio over a broad wavelength range from 1.52 to 1.60 µm. The fabricated device occupied a compact footprint of only 2.88 µm × 2.88 µm. The measured average excess losses and crosstalks for both modes were respectively less than 1.5 dB and -20 dB from 1.52 to 1.58 µm for both TE0 and TE1, which are consistent with the numerical simulations.