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BACKGROUND: Plant growth-promoting rhizobacteria (PGPR), as a group of environmentally friendly bacteria growing in the rhizosphere of plants, play an important role in plant growth and development and resistance to environmental stresses. However, their limited understanding has led to the fact that their large-scale use in agriculture is still scarce, and the mechanisms by which beneficial bacteria are selected by plants and how they interact with them are still unclear. METHOD: In this study, we investigated the interaction between the auxin-producing strain Bacillus aryabhattai LAD and maize roots, and performed transcriptomic and metabolomic analyses of Bacillus aryabhattai LAD after treatment with maize root secretions(RS). RESULTS: Our results show that there is a feedback effect between the plant immune system and bacterial auxin. Bacteria activate the immune response of plant roots to produce reactive oxygen species(ROS), which in turn stimulates bacteria to synthesize IAA, and the synthesized IAA further promotes plant growth. Under the condition of co-culture with LAD, the main root length, seedling length, root surface area and root volume of maize increased by 197%, 107%, 89% and 75%, respectively. In addition, the results of transcriptome metabolome analysis showed that LAD was significantly enriched in amino acid metabolism, carbohydrate metabolism and lipid metabolism pathways after RS treatment, including 93 differentially expressed genes and 45 differentially accumulated metabolites. CONCLUSION: Our findings not only provide a relevant model for exploring the effects of plant-soil microbial interactions on plant defense functions and thereby promoting plant growth, but also lay a solid foundation for the future large-scale use of PGPR in agriculture for sustainable agricultural development.

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Recently, virtual staining techniques have attracted more and more attention, which can help bypass the chemical staining process of traditional histopathological examination, saving time and resources. Meanwhile, as an emerging tool to characterize specific tissue structures in a label-free manner, the Mueller matrix microscopy can supplement more structural information that may not be apparent in bright-field images. In this Letter, we propose the Mueller matrix guided generative adversarial networks (MMG-GAN). By integrating polarization information provided by the Mueller matrix microscopy, the MMG-GAN enables the effective transformation of input H&E-stained images into corresponding Masson trichrome (MT)-stained images. The experimental results demonstrate the accuracy of the generated images by MMG-GAN and reveal the potential for more stain transformation tasks by incorporating the Mueller matrix polarization information, laying the foundation for future polarimetry-assisted digital pathology.

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PURPOSE: Button battery nasal impactions pose serious risks due to complications and the need for prompt removal, yet research on interventions remains limited due to its rare occurrence. To delineate the clinical manifestations of nasal foreign bodies associated with button batteries and to explore treatment approaches focused on minimizing the reliance on general anesthesia and surgical interventions. METHODS: This study focuses on 176 cases of children who received treatment for nasal cavity button battery impactions. It encompasses various factors including age, gender, battery location, impaction duration, methods of extraction, and associated complications. RESULTS: The incidence of nasal button battery cases among nasal foreign body instances was 1.16%, with a majority being males (60.23%) aged 1-5 years (98.29%). Utilizing a specially designed nasal foreign body hook and following established treatment protocols enabled the successful outpatient management of the majority of cases. Only 12 cases (6.82%) necessitated removal under general anesthesia due to management challenges in an outpatient setting. Furthermore, our findings indicated no linear correlation between the duration of battery retention and the risk of nasal septal perforation, which was observed in 31 cases (17.61%). CONCLUSION: Nasal foreign bodies caused by button batteries in children demand urgent attention due to their potentially grave outcomes. Our research is directed towards enhancing diagnostic and therapeutic strategies to bolster the success rates of outpatient removal, curtail the duration of foreign body retention, and diminish the reliance on general anesthesia.

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Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease that is often accompanied by mental health disorders. However, the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain. This study analyzed widely targeted metabolomic data of expressed prostatic secretions (EPS) and plasma to reveal the underlying pathological mechanisms of CP/CPPS. A total of 24 CP/CPPS patients from The Second Nanning People's Hospital (Nanning, China), and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University (Nanning, China) were enrolled. The indicators related to CP/CPPS and psychiatric symptoms were recorded. Differential analysis, coexpression network analysis, and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS. The crucial links between EPS and plasma were further investigated. The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals. Pathway analysis revealed dysregulation of amino acid metabolism, lipid metabolism, and the citrate cycle in EPS. The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes. Moreover, the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS. Overall, metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage, energy metabolism abnormalities, neurological impairment, and immune dysregulation. These alterations may be associated with chronic pain, voiding symptoms, reduced fertility, and depression in CP/CPPS. This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets.

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A Mueller matrix covers all the polarization information of the measured sample, however the combination of its 16 elements is sometimes not intuitive enough to describe and identify the key characteristics of polarization changes. Within the Poincaré sphere system, this study achieves a spatial representation of the Mueller matrix: the Global-Polarization Stokes Ellipsoid (GPSE). With the help of Monte Carlo simulations combined with anisotropic tissue models, three basic characteristic parameters of GPSE are proposed and explained, where the V parameter represents polarization maintenance ability, and the E and D† parameters represent the degree of anisotropy. Furthermore, based on GPSE system, a dynamic analysis of skeletal muscle dehydration process demonstrates the monitoring effect of GPSE from an application perspective, while confirming its robustness and accuracy.

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Objective: Diabetic nephropathy (DN) is a serious complication that may occur during the later stages of diabetes, and can be further exacerbated by podocyte damage. Piperazine ferulate (PF) has well-defined nephroprotective effects and is used clinically in the treatment of chronic nephritis and other kidney diseases. However, the renoprotective effects and mechanisms of PF on DN are not clear. This study aims to investigate the protective effect of PF on DN and its mechanism of action, to inform the clinical application of PF in DN treatment. Methods: Network pharmacology was performed to predict the mechanism of action of PF in DN. Male Sprague Dawley rats were intraperitoneally injected with STZ (60 mg/kg) to establish a DN model, and then assessed for renal injury after 12 weeks of administration. In vitro, rat podocytes were treated with 25 mmol/L glucose and cultured for 24 h, followed by an assessment of cell injury. Results: Our results showed that PF significantly improved renal function, reduced renal pathological changes, decreased inflammatory response, and alleviated podocyte damage in DN rats. PF also attenuated glucose-induced podocyte injury in vitro. Regarding molecular mechanisms, our study demonstrated that PF downregulated the expression of genes and proteins related to AGE-RAGE-mediated inflammatory signaling. Conclusion: In summary, PF exerts its renoprotective effects by decreasing inflammation and protecting against podocyte injury through the inhibition of the AGE/RAGE/NF-κB/NLRP3 pathway. Overall, these data support the clinical potential of PF as a renoprotective agent in DN.

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OBJECTIVES: The present study aimed to investigate the relationship between male hormones and metabolic dysfunction-associated fatty liver disease (MAFLD) in males. METHODS: Data from the Fangchenggang Area Male Health and Examination Survey (FAMHES) were used to analyze the male hormone levels between MAFLD patients and controls. Univariate and multivariate logistic regression analyses were performed to identify risk factors for MAFLD. Receiver operating characteristic curve analysis was used to assess the diagnostic performance of male hormones for MAFLD. RESULT: A total of 1578 individuals were included, with 482 individuals (30.54%) of MAFLD, including 293 (18.57%) with mild disease and 189 (11.98%) with moderate-to-severe disease. The MAFLD patients were significantly older than those without MAFLD. The LH, FSH, and SHBG levels in the MAFLD patients were significantly greater than those in the control group. Age, FSH, LH, SHBG, and estradiol were all risk factors for MAFLD. Age, FSH, and LH were risk factors for moderate-to-severe MAFLD. FSH was an independent risk factor for MAFLD and moderate-to-severe MAFLD. FSH showed an excellent diagnostic value, with an AUC of 0.992 alone and 0.996 after adjusting age. CONCLUSIONS: Our findings indicate that FSH may be a potential diagnostic and predictive biomarker for MAFLD.

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Fungal biofilm is a microbial community composed of fungal cells and extracellular polymeric substances (EPS). In recent years, fungal biofilms have played an increasingly important role in many fields. However, there are few studies on fungal biofilms and their related applications and development are still far from enough. Therefore, this review summarizes the composition and function of EPS in fungal biofilms, and improves and refines the formation process of fungal biofilms according to the latest viewpoints. Moreover, based on the study of Saccharomyces cerevisiae and Candida albicans, this review summarizes the gene regulation network of fungal biofilm synthesis, which is crucial for systematically understanding the molecular mechanism of fungal biofilm formation. It is of great significance to further develop effective methods at the molecular level to control harmful biofilms or enhance and regulate the formation of beneficial biofilms. Finally, the quorum sensing factors and mixed biofilms formed by fungi in the current research of fungal biofilms are summarized. These results will help to deepen the understanding of the formation process and internal regulation mechanism of fungal biofilm, provide reference for the study of EPS composition and structure, formation, regulation, group behavior and mixed biofilm formation of other fungal biofilms, and provide strategies and theoretical basis for the control, development and utilization of fungal biofilms.

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Mueller matrix microscopy can provide comprehensive polarization-related optical and structural information of biomedical samples label-freely. Thus, it is regarded as an emerging powerful tool for pathological diagnosis. However, the staining dyes have different optical properties and staining mechanisms, which can put influence on Mueller matrix microscopic measurement. In this Letter, we quantitatively analyze the polarization enhancement mechanism from hematoxylin and eosin (H&E) staining in multispectral Mueller matrix microscopy. We examine the influence of hematoxylin and eosin dyes on Mueller matrix-derived polarization characteristics of fibrous tissue structures. Combined with Monte Carlo simulations, we explain how the dyes enhance diattenuation and linear retardance as the illumination wavelength changed. In addition, it is demonstrated that by choosing an appropriate incident wavelength, more visual Mueller matrix polarimetric information can be observed of the H&E stained tissue sample. The findings can lay the foundation for the future Mueller matrix-assisted digital pathology.

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AIMS: Diabetic kidney disease (DKD) significantly impairs quality of life in individuals with diabetes mellitus (DM). The influence of the Dietary Inflammatory Index (DII) on DKD, which is associated with adverse health outcomes, is not well-understood. METHODS: We analyzed 2712 subjects from the National Health and Nutrition Examination Survey (NHANES) spanning 2011-2018, aiming to elucidate the relationship between DII and DKD. RESULTS: DKD was diagnosed in 1016 participants (37.46%). Elevated DII levels were significantly associated with an increased DKD risk, as evidenced by multivariate logistic regression (Odds Ratio [OR] = 1.40, 95% Confidence Interval [CI] 1.12-1.75, P < 0.05). Further analysis after adjusting for covariates highlighted a notable non-linear correlation between DII and DKD risk, at DII values below 0.45, the risk of DKD increases with higher DII levels, whereas it stabilizes beyond this point. Subgroup analysis additionally revealed that diabetic men have a significantly higher DKD risk compared to women (P < 0.05). CONCLUSION: Our study indicates a pronounced link between higher DII scores and increased risk of DKD among DM patients. These findings underscore the paramount importance of dietary management in DM treatment, stressing the need for interventions focused on reducing dietary inflammation to decelerate DKD progression.

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ETHNOPHARMACOLOGICAL RELEVANCE: Citri Reticulatae Pericarpium (CRP), known as Chen Pi in China, is the most commonly used medicine for regulating qi. As a traditional medicine, CRP has been extensively used in the clinical treatment of nausea, vomiting, cough and phlegm for thousands of years. It is mainly distributed in Guangdong, Sichuan, Fujian and Zhejiang in China. Due to its high frequency of use, many scholars have conducted a lot of research on it and the related chemical constituents it contains. In this review, the research progress on phytochemistry, pharmacology, pharmacokinetics and toxicology of CRP are summarized. AIM OF THE REVIEW: The review aims to sort out the methods of extraction and purification, pharmacological activities and mechanisms of action, pharmacokinetics and toxicology of the chemical constituents in CRP, in order to elaborate the future research directions and challenges for the study of CRP and related chemical constituents. MATERIALS AND METHODS: Valid and comprehensive relevant information was collected from China National Knowledge Infrastructure, Web of Science, PubMed and so on. RESULTS: CRP contains a variety of compounds, of which terpenes, flavonoids and alkaloids are the main components, and they are also the primary bioactive components that play a pharmacological role. Flavonoids and terpenes are extracted and purified by aqueous and alcoholic extraction methods, assisted by ultrasonic and microwave extraction, in order to achieve higher yields with less resources. Pharmacological studies have shown that CRP possesses a variety of highly active chemical components and a wide range of pharmacological activities, including anti-tumor, anti-inflammatory, immunomodulatory, hepatoprotective, therapeutic for cardiovascular-related disorders, antioxidant, antibacterial, and neuroprotective effects. CONCLUSIONS: There is a diversity in the chemical compositions of CRP, which have multiple biological activities and promising applications. However, the pharmacological activities of CRP are mainly dependent on the action of its chemical components, but the relationship between the structure of chemical components and the biological effects has not been thoroughly investigated, and therefore, the structure-activity relationship is an issue that needs to be elucidated urgently. In addition, the pharmacokinetic studies of the relevant components can be further deepened and the correlation studies between pharmacological effects and syndromes of TCM can be expanded to ensure the effectiveness and rationality of CRP for human use.

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Formononetin (FMNT) is a secondary metabolite of flavonoids abundant in legumes and graminaceous plants such as Astragalus mongholicus Bunge [Fabaceae; Astragali radix] and Avena sativa L. [Poaceae]. Astragalus is traditionally used in Asia countries such as China, Korea and Mongolia to treat inflammatory diseases, immune disorders and cancers. In recent years, inflammation and oxidative stress have been found to be associated with many diseases. A large number of pharmacological studies have shown that FMNT, an important bioactive metabolite of Astragalus, has a profoundly anti-inflammatory and antioxidant potential. This review focuses on providing comprehensive and up-to-date findings on the efficacy of the molecular targets and mechanisms involve of FMNT and its derivatives against inflammation and oxidative stress in both in vitro and in vivo. Relevant literature on FMNT against inflammation and oxidative stress between 2013 and 2023 were analyzed. FMNT has antioxidant and anti-inflammatory potential and shows mild or no toxicity in various diseases. Moreover, in the medical field, FMNT has shown potential in the prevention and treatment of cancers, neurological diseases, fibrotic diseases, allergic diseases, metabolic diseases, cardiovascular diseases, gastrointestinal diseases and autoimmune diseases. Thus, it is expected to be utilized in more products in the medical, food and cosmetic industries in the future.

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As a complex anisotropic medium, variation in birefringence within biological tissues is closely associated with numerous physiological behaviors and phenomena. In this Letter, we propose a polarization feature fusion method and corresponding polarimetric parameters, which exhibit excellent performance of capturing the birefringence dynamic variation process in complex anisotropic media. By employing the feature fusion method, we combine and transform polarization basis parameters (PBPs) to derive fused polarization feature parameters (FPPs) with explicit expressions. Subsequently, we conduct Monte Carlo (MC) simulation to demonstrate the effectiveness of the proposed FPPs from two variation dimensions of birefringence direction θ and modulus Δn. Leveraging mathematical modeling and linear transformations, we investigate and abstract their response patterns concerning θ and Δn. Finally, the experiments confirm that the FPPs show superior adaptability and interpretability in characterizing the birefringence dynamic process of turbid media. The findings presented in this study provide new, to the best of our knowledge, methodological insights of information extraction for computational polarimetry in biomedical research.

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This study aims to explore the potential mechanism of action in the intervention of acute lung injury(ALI) based on the blood entry components of Ganke Granules in rats and in conjunction with network pharmacology, molecular docking, and animal experimental validation. The blood entry components of Ganke Granules in rats were imported into the SwissTargetPrediction platform to predict drug targets, and ALI-related targets were collected from the disease database. Intersections were taken, and protein-protein interaction(PPI) networks were constructed to screen the core targets, followed by Gene Ontology(GO) functional and Kyoto encyclopedia of genes and gnomes(KEGG) pathway enrichment analyses. A "blood entry components-target-pathway-disease" network was constructed, and the core components for disease intervention based on their topological parameters were screened. Molecular docking was used to predict the binding ability of the core components to key targets. The key targets of Ganke Granules in the intervention of ALI were verified by the lipopolysaccharide(LPS)-induced ALI mouse model. Through PPI topological parameter analysis, the top six key targets of STAT3, SRC, HSP90AA1, MAPK3, HRAS, and MAPK1 related to ALI were obtained. GO functional analysis showed that it was mainly related to ERK1 and ERK2 cascade, inflammatory response, and response to LPS. KEGG analysis showed that the main enrichment pathways were MAPK, neutrophil extracellular trap(NET) formation, and so on. Six core components(schizantherin B, schisandrin, besigomsin, harpagoside, isotectorigenin, and trachelanthamine) were filtered out by the "blood entry components-target-pathway-disease" network based on the analysis of topological parameters. Molecular docking results showed that the six core components and Tectoridin with the highest content in the granules had a high affinity with the key targets of MAPK3, SRC, MAPK1, and STAT3. In vivo experiment results showed that compared with the model group, Ganke Granules could effectively alleviate LPS-induced histopathological injury in the lungs of mice and reduce the percentage of inflammatory infiltration. The total protein content, nitric oxide(NO) level, myeloperoxidase(MPO) content, tumor necrosis factor-α(TNF-α), gamma interferon(IFN-γ), interleukin-1ß(IL-1ß), interleukin-6(IL-6), vascular endothelial growth factor(VEGF), and chemokine(C-X-C motif) ligand 1(CXCL1) chemokines in bronchoalveolar lavage fluid(BALF) were decreased, and the expression levels of lymphocyte antigen 6G(Ly6G), citrullinated histones 3(Cit-H3), and phosphorylated proteins SRC, ERK1/2, and STAT3 in lung tissue were significantly down-regulated. In conclusion, Ganke Granules could effectively inhibit the inflammatory response of ALI induced by LPS, protect lung tissue, regulate the release of inflammatory factors, and inhibit neutrophil infiltration and NET formation, and the mechanism of action may be related to inhibiting the activation of SRC/ERK1/2/STAT3 signaling pathway.

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The Chinese tree shrew ( Tupaia belangeri chinensis) has emerged as a promising model for investigating adrenal steroid synthesis, but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans. Here, we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing, spatial transcriptome analysis, mass spectrometry, and immunohistochemistry. We compared the transcriptomes of various adrenal cell types across tree shrews, humans, macaques, and mice. Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans, including CYP11B2, CYP11B1, CYB5A, and CHGA. Biochemical analysis confirmed the production of aldosterone, cortisol, and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands. Furthermore, genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome, primary aldosteronism, hypertension, and related disorders in humans based on genome-wide association studies. Overall, this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland. Our comprehensive results (publicly available at http://gxmujyzmolab.cn:16245/scAGMap/) should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

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Porous suspended particles are hazardous to human health due to their strong absorption capacity for toxic substances. A fast, accurate, in situ and high-throughput method to characterize the microporous structure of porous particles has extensive application value. The polarization changes during the light scattering of aerosol particles are highly sensitive to their microstructural properties, such as pore size and porosity. In this study, we propose an overlapping sphere model based on the discrete dipole approximation (DDA) to calculate the polarization scattering characteristics of porous particles. By combining scattering calculations with multi-dimensional polarization indexes measured by a multi-angle polarized scattering vector detection system, we achieve the identification and classification of pore-type components in suspended particles. The maximum deviation based on multiple indexes is less than 0.16% for the proportion analysis of mixed particles. Simultaneously, we develop a quantitative inversion algorithm on pore size and porosity. The inversion results of the three porous polymer particles support the validity and feasibility of our method, where the inversion error of partial particles is less than 4% for pore size and less than 6% for porosity. The study demonstrates the potential of polarization measurements and index systems applied in characterizing the micropore structure of suspended particles.

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Farnesyl pyrophosphate synthase (FPPS) catalyzes the synthesis of C15 farnesyl diphosphate (FPP) from C5 dimethylallyl diphosphate (DMAPP) and two or three C5 isopentenyl diphosphates (IPPs). FPP is an important precursor for the synthesis of isoprenoids and is involved in multiple metabolic pathways. Here, farnesyl pyrophosphate synthase from Sporobolomyces pararoseus NGR (SpFPPS) was isolated and expressed by the prokaryotic expression system. The SpFPPS full-length genomic DNA and cDNA are 1566 bp and 1053 bp, respectively. This gene encodes a 350-amino acid protein with a predicted molecular mass of 40.33 kDa and a molecular weight of 58.03 kDa (40.33 kDa + 17.7 kDa), as detected by SDS-PAGE. The function of SpFPPS was identified by induction, purification, protein concentration and in vitro enzymatic activity experiments. Structural analysis showed that Y90 was essential for chain termination and changing the substrate scope. Site-directed mutation of Y90 to the smaller side-chain amino acids alanine (A) and lysine (K) showed in vitro that wt-SpFPPS catalyzed the condensation of the substrate DMAPP or geranyl diphosphate (GPP) with IPP at apparent saturation to synthesize FPP as the sole product and that the mutant protein SpFPPS-Y90A synthesized FPP and C20 geranylgeranyl diphosphate (GGPP), while SpFPPS-Y90K hydrolyzed the substrate GGPP. Our results showed that FPPS in S. pararoseus encodes the SpFPPS protein and that the amino acid substitution at Y90 changed the distribution of SpFPPS-catalyzed products. This provides a baseline for potentially regulating SpFPPS downstream products and improving the carotenoid biosynthesis pathway.

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Polarization imaging and sensing techniques have shown great potential for biomedical and clinical applications. As a novel optical biosensing technology, Mueller matrix polarimetry can provide abundant microstructural information of tissue samples. However, polarimetric aberrations, which lead to inaccurate characterization of polarization properties, can be induced by uneven biomedical sample surfaces while measuring Mueller matrices with complex spatial illuminations. In this study, we analyze the detailed features of complex spatial illumination-induced aberrations by measuring the backscattering Mueller matrices of experimental phantom and tissue samples. We obtain the aberrations under different spatial illumination schemes in Mueller matrix imaging. Furthermore, we give the corresponding suggestions for selecting appropriate illumination schemes to extract specific polarization properties, and then provide strategies to alleviate polarimetric aberrations by adjusting the incident and detection angles in Mueller matrix imaging. The optimized scheme gives critical criteria for the spatial illumination scheme selection of non-collinear backscattering Mueller matrix measurements, which can be helpful for the further development of quantitative tissue polarimetric imaging and biosensing.

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Background: Pathophysiology plays a significant role in the scientific study of ischemic stroke, and has attracted increasing interest from researchers in the field. However, a comprehensive bibliometric analysis is lacking in this field. The purpose of this study is to identify the current research status and hotspots of ischemic stroke pathophysiology from a bibliometric perspective. Methods: The Web of Science Core Collection database was searched for articles published from 1990 to 2022. CiteSpace, VOSviewer, and R package "bibliometrix" software were used to analyze countries/regions, institutions, journals, authors, papers, and keywords to predict the latest trends in ischemic stroke pathophysiology research. Results: This analysis collected 7578 records of ischemic stroke pathophysiology. China and America emerged as the leading countries in this field, with Harvard University being the most active institution. Among journals and authors in this field, journal Stroke and author Gregory YH Lip published the most papers, while Nature Medicine was the journal with the highest citation per article. Keywords and co-citation clusters were closely related to "central nervous system", "mechanisms", "biochemistry & molecular biology" and "radiology, nuclear medicine & medical imaging", while other related fields, such as peripheral organs damage induced by the central nervous system and rehabilitation after ischemic stroke, require further research efforts. Conclusion: This is the first bibliometric study that comprehensively mapped out the knowledge structure and development trends of ischemic stroke pathophysiology in recent 32 years, which may provide a reference for scholars to explore ischemic stroke pathophysiology.

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The combination of Chaidangbo (CDB) is an antidepressant traditional Chinese medicine (TCM) prescription simplified by Xiaoyaosan (a classic antidepressant TCM prescription) through dismantling research, which has the effect of dispersing stagnated liver qi and nourishing blood in TCM theory. Although the antidepressant effect of CBD has been confirmed in animal studies, the material basis and possible molecular mechanism for antidepressant activity in CBD have not been clearly elucidated. Herein, we investigated the effects and potential mechanisms of CDB antidepressant fraction (petroleum ether fraction of CDB, PEFC) on chronic unpredictable mild stress (CUMS)-induced depression-like behavior in mice using network pharmacology and metabolomics. First, a UPLC-QE/MS was employed to identify the components of PEFC. To extract active ingredients, SwissADME screening was used to the real PEFC components that were found. Potential PEFC antidepressant targets were predicted based on a network pharmacology approach, and a pathway enrichment analysis was performed for the predicted targets. Afterward, a CUMS mouse depression model was established and LC-MS-based untargeted hippocampal metabolomics was performed to identify differential metabolites, and related metabolic pathways. Finally, the protein expressions in mouse hippocampi were determined by Western blot to validate the network pharmacology and metabolomics deduction. A total of 16 active compounds were screened in SwissADME that acted on 73 core targets of depression, including STAT3, MAPKs, and NR3C1; KEGG enrichment analysis showed that PEFC modulated signaling pathways such as PI3K-Akt signaling pathway, endocrine resistance, and MAPK to exert antidepressant effects. PEFC significantly reversed abnormalities of hippocampus metabolites in CUMS mice, mainly affecting the synthesis and metabolism of glycine, serine, and threonine, impacting catecholamine transfer and cholinergic synapses and regulating the activity of the mTOR signaling pathway. Furthermore, Western blot analysis confirmed that PEFC significantly influenced the main protein levels of the PI3K/Akt/mTOR signaling pathways in the hippocampus of mice subjected to CUMS. This study integrated metabolomics, network pharmacology and biological verification to explore the potential mechanism of PEFC in treating depression, which is related to the regulation of amino acid metabolism dysfunction and the activation of PI3K/Akt/mTOR signaling pathways in the hippocampus. The comprehensive strategy also provided a reasonable way for unveiling the pharmacodynamic mechanisms of multi-components, multi-targets, and multi-pathways in TCM with antidepressant effect.