Deep neural network for the prediction of KRAS, NRAS, and BRAF genotypes in left-sided colorectal cancer based on histopathologic images.

BACKGROUND: The KRAS, NRAS, and BRAF genotypes are critical for selecting targeted therapies for patients with metastatic colorectal cancer (mCRC). Here, we aimed to develop a deep learning model that utilizes pathologic whole-slide images (WSIs) to accurately predict the status of KRAS, NRAS, and BRAFV600E. METHODS: 129 patients with left-sided colon cancer and rectal cancer from the Third Affiliated Hospital of Sun Yat-sen University were assigned to the training and testing cohorts. Utilizing three convolutional neural networks (ResNet18, ResNet50, and Inception v3), we extracted 206 pathological features from H&E-stained WSIs, serving as the foundation for constructing specific pathological models. A clinical feature model was then developed, with carcinoembryonic antigen (CEA) identified through comprehensive multiple regression analysis as the key biomarker. Subsequently, these two models were combined to create a clinical-pathological integrated model, resulting in a total of three genetic prediction models. RESULT: 103 patients were evaluated in the training cohort (1782,302 image tiles), while the remaining 26 patients were enrolled in the testing cohort (489,481 image tiles). Compared with the clinical model and the pathology model, the combined model which incorporated CEA levels and pathological signatures, showed increased predictive ability, with an area under the curve (AUC) of 0.96 in the training and an AUC of 0.83 in the testing cohort, accompanied by a high positive predictive value (PPV 0.92). CONCLUSION: The combined model demonstrated a considerable ability to accurately predict the status of KRAS, NRAS, and BRAFV600E in patients with left-sided colorectal cancer, with potential application to assist doctors in developing targeted treatment strategies for mCRC patients, and effectively identifying mutations and eliminating the need for confirmatory genetic testing.

Cytochemical localization and synthesis mechanism of the glucomannan in pseudobulbs of Bletilla striata Reichb. f.

The dried pseudobulbs of Bletilla striata, an important traditional Chinese medicine named BaiJi, have an extraordinary polysaccharide content and excellent prospects for medicinal effects. However, the distribution and molecular mechanism underlying biosynthesis are poorly understood. In this study, chemical and immunologic analyses were performed in representative tissues of B. striata, and the results showed that what are conventionally termed Bletilla striata polysaccharides (BSPs) are water-soluble polysaccharides deposited only in pseudobulbs. The structural component of BSPs is glucomannan, with a mannose:glucose mass ratio of ~3:2. BSPs are present in the parenchyma of the pseudobulbs in cells known as glucomannan idioblasts and distributed in the cytoplasm within cellular membranes, but are not contained in the vacuole. Comparative transcriptomics and bioinformatics analyses mapped the pathway from sucrose to BSP and identified BsGPI, BsmanA, and BsCSLAs as the key genes of BSP biosynthesis, suggesting that the functional differentiation of the cellulose synthase-like family A (CSLA) may be critical for the flow of glucomannan to the BSP or cell wall. Subsequently, virus-mediated gene silencing showed that silencing of two CSLAs (Bs03G11846 and Bs03G11849) led to a decrease in BSP content, and yeast two-hybrid and luciferase complementation experiments confirmed that four CSLAs (Bs03G11846, Bs03G11847, Bs03G11848, and Bs03G11849) can form homo- or heterodimers, suggesting that multiple CSLAs may form a large complex that functions in BSP synthesis. Our results provide cytological evidence of BSP and describe the isolation and characterization of candidate genes involved in BSP synthesis, laying a solid foundation for further research on its regulation mechanisms and the genetic engineering breeding of B. striata.

Eliminating the Adverse Impact of Composition Modulation in Perovskite Light-Emitting Diodes toward Ultra-High Brightness and Stability.

Excess ammonium halides as composition additives are widely employed in perovskite light-emitting diodes (PeLEDs), aiming to achieve high performance by controlling crystallinity and passivating defects. However, an in-depth understanding of whether excess organoammonium components affect the film physical/electrical properties and the resultant device instability is still lacking. Here, the trade-off between the performance and stability in high-efficiency formamidinium lead iodide (FAPbI3)-based PeLEDs with excess ammonium halides is pointed, and the underlying mechanism is explored. Systematic experimental and theoretical studies reveal that excess halide salt-induced ion-doping largely alters the PeLEDs properties (e.g., carrier injection, field-dependent ion-drifting, defect physics, and phase stability). A surface clean assisted cross-linking strategy is demonstrated to eliminate the adverse impact of composition modulation and boost the operational stability without sacrificing the efficiency, achieving a high efficiency of 23.6%, a high radiance of 964 W sr-1 m-2 (The highest value for FAPbI3 based PeLEDs), and a prolong lifetime of 106.1 h at large direct current density (100 mA cm-2), concurrently. The findings uncovered an important link between excess halide salts and the device performance, providing a guideline for rational design of stable, bright, and high efficiency PeLEDs.

Protective effect of Danshensu against neurotoxicity induced by monosodium glutamate in adult mice and their offspring.

Excessive neuronal excitation by glutamate is a well-established cause of neurotoxicity, leading to severe impairment of brain function. Excitotoxicity is a key factor in numerous neurodegenerative conditions. In this study, we investigated the neuroprotective effects of Danshensu (DSS) against monosodium glutamate (MSG)-induced neurotoxicity in adult mice and their offspring. We randomly divided one hundred 8-week-old Kunming mice (equal number of males and females) into a control group and an experimental group. The experimental group was further subdivided into various treatment groups, including MSG gavage treatment, bwbw DSS treatment group 1 (bwbw DSS treatment group 2, a drug control group, and a normal control group (receiving an equal volume of physiological saline for ten consecutive days). Additionally, another one hundred healthy 8-week-old Kunming mice were similarly divided into groups and treated. These mice were paired randomly (one male and one female) and pregnant females were housed separately to obtain offspring. Subsequently, we conducted histological and behavioral analyses on adult mice and their offspring. MSG treatment induced significant cellular edema and hippocampal damage in both the treated mice and their offspring. However, varying doses of DSS effectively counteracted the neurotoxic effects of MSG, with no adverse impact on brain tissue structure or neural function in either adult mice or their offspring. Behavioral experiments further confirmed that DSS exerted a substantial protective effect against MSG-induced impairment of learning and memory in the treated adult mice and their offspring, in addition to mitigating central nervous system overexcitation and inhibiting exploratory behavior. In conclusion, DSS exerts significant protective effects against MSG-induced neurotoxicity in both adult mice and their offspring.

Solid phase microextraction device coupled with miniature mass spectrometry and mathematical model of its ion chronogram.

Modern solid phase microextraction (SPME) device linked with mass spectrometry (SPME-MS) has evolved from producing ion chronogram as flat noisy signal to as unimodal-like signal. We designed a SPME device, which is closer in morphology to LC column, linked it with a miniature mass spectrometer (SPME-Mini MS), and proposed a mathematical model that elution of compound from the SPME device is equivalent to overlay of elution of the compound from the infinite LC columns with the lengths between 0 and the length of the device and it can generate an ion chronogram as right-skew unimodal signal. Rhodamine B as analyte was used for experimental verification and its unimodal signal was used to fit the parameters of a computer simulation program based on the model. The experimental results and simulations empirically cross-confirmed that SPME-Mini MS can generate ion chronogram as clean right-skew unimodal signal. Furthermore, the SPME-Mini MS system was used for quantitative analysis of psychotropic drugs (i.e. risperidone and aripiprazole) in artificial urine. The results preliminarily demonstrated that the system can utilize area under unimodal signal for quantitative analysis and has potential to be applied for on-site, fast and accurate quantification of drugs and other compounds.

Neuroprotective neolignan glycosides from the pseudobulbs of Bletilla striata.

Four undescribed neolignan glycosides, bletineosides A-D (1-4) were isolated from the pseudobulbs of Bletilla striata. Their structures with absolute configurations were elucidated on the basis of spectroscopic analyses, along with acidic hydrolysis reactions and ECD experiments. All isolates were evaluated for their neuroprotective activities against glutamate-induced PC12 cell injury. Compound 3 and 4 showed significantly neuroprotective effects at the concentration of 10 µM when compared with the model group. Compounds 1-4 represented the first examples of neolignan glycosides from the genus Bletilla. This study disclosed the potency of Bletilla striata as a new source of anti-neurodegenerative agents.

Human-murine chimeric autoantibodies with high affinity and specificity for systemic sclerosis.

Scleroderma 70 (Scl-70) is commonly used in the clinic for aiding systemic sclerosis (SSc) diagnosis due to its recognition as autoantibodies in the serum of SSc patients. However, obtaining sera positive for anti-Scl-70 antibody can be challenging; therefore, there is an urgent need to develop a specific, sensitive, and easily available reference for SSc diagnosis. In this study, murine-sourced scFv library were screened by phage display technology against human Scl-70, and the scFvs with high affinity were constructed into humanized antibodies for clinical application. Finally, ten high-affinity scFv fragments were obtained. Three fragments (2A, 2AB, and 2HD) were select for humanization. The physicochemical properties of the amino acid sequence, three-dimensional structural basis, and electrostatic potential distribution of the protein surface of different scFv fragments revealed differences in the electrostatic potential of their CDR regions determined their affinity for Scl-70 and expression. Notably, the specificity test showed the half-maximal effective concentration values of the three humanized antibodies were lower than that of positive patient serum. Moreover, these humanized antibodies showed high specificity for Scl-70 in diagnostic immunoassays for ANA. Among these three antibodies, 2A exhibited most positive electrostatic potential on the surface of the CDRs and highest affinity and specificity for Scl-70 but with least expression level; thus, it may provide new foundations for developing enhanced diagnostic strategies for SSc.

Curcumin combining temozolomide formed localized nanogel for inhibition of postsurgical chemoresistant glioblastoma.

Aim: To investigate the use of nanoparticle (NP)-encapsulated injectable thermosensitive hydrogel-formed nanogel for inhibition of postsurgical residual temozolomide (TMZ)-resistant glioblastoma (GBM) recurrence. Materials & methods: Curcumin (Cur) was coloaded with TMZ into PEG-PLGA NPs, then NPs were further encapsulated into a thermosensitive hydrogel to form a nanogel, which was injected into the resection cavity of the GBM postsurgery. Results: The prepared nanogel displayed excellent drug-loading capacity and long-term drug release. Estimated survival characteristics demonstrated that the nanogel could play a significant role in TMZ-resistant tumor inhibition with low drug-induced toxicity. The originally designed ratio of Cur/TMZ was sustained, making it an effective therapeutic outcome. Conclusion: Cur-combined TMZ-formed nanogels can be a promising candidate for the local inhibition of GBM recurrence.

In this study, the animal model used was rats suffering residual brain tumor after resection. The selected drugs were temozolomide, a first-line chemotherapeutic drug for the clinical treatment of glioma, and curcumin, an extract from the ginger plant. With the use of temozolomide, brain glioma cells gradually develop resistance, resulting in poor efficacy of temozolomide. Therefore, the purpose of this study was to construct a drug-delivery system for temozolomide-resistant brain glioma residual tumor after surgery, namely, a temperature-sensitive gel containing drug-carrying nanopreparations ­ the so-called nanogels. This drug-delivery system can directly deliver drugs to residual tumor cells in situ after surgery. In situ drug-delivery systems can reduce the dose of drugs consumed and increase their potency compared to oral or intravenous administration.

Clinical analysis of anastomotic fistula after anal preservation in 358 cases of rectal cancer and construction of risk prediction model: a single-center retrospective study.

OBJECTIVE: To develop and validate a simple prediction model for postoperative anastomotic leakage (AL) in patients with rectal cancer who underwent Dixon surgery by combining preoperative and intraoperative risk factors. METHODS: We conducted a retrospective study on 358 patients who underwent Dixon surgery for rectal cancer in the Affiliated Hospital of Youjiang Medical University for Nationalities (Guangxi Zhuang Autonomous Region, China). Based on logistic regression, the prediction model of AL after Dixon surgery was established and verified. RESULTS: The incidence of postoperative AL in these patients was 9.2% (33/358). The results of logistic regression analysis showed that age ≥60 years, male, Tumor-Node-Metastasis (TNM) stage ≥IIIa, preoperative obstruction, and the distance from the tumor to the anus ≤7 cm were the risk factors for AL after Dixon surgery, and intraoperative defunctioning stoma was the protective factor for AL after rectal Dixon surgery (all P<0.05). The prediction model construction: Risk score =-4.275 + 0.851 × age + 1.047 × sex + 0.851 × distance + 0.934 × stage + 0.983 × obstruction. The area under receiver operating characteristic curve (ROC-AUC) was 0.762 (95% CI: 0.667-0.856). The best cutoff, sensitivity and specificity were 0.14, 79.60%, and 83.10%, respectively. Hosmer-Lemeshow: X2=6.876, P=0.550. Clinical validation results: the sensitivity, specificity, and accuracy of the model were 82.05%, 80.06%, and 80.25%, respectively. CONCLUSIONS: Both preoperative and intraoperative risk factors were used in the prognostic model. The prediction model established on this basis was well differentiated and highly calibrated, providing a good reference for the clinical prediction model of postoperative AL in rectal cancer patients undergoing Dixon surgery.

Effect of Passivating Molecules and Antisolvents on Lifetime of Green Dion-Jacobson Perovskite Light-Emitting Diodes.

We investigated the influence of two passivating molecules containing a P═O group on the performance of quasi-2D Dion-Jacobson halide perovskite light-emitting diodes, namely, triphenylphosphine oxide (TPPO) and diphenyl-4-triphenylsilylphenyl phosphine oxide (TSPO1). We found that both passivating molecules lead to increased efficiency compared to control devices, while they had opposite effects on device lifetime, with a decrease observed for TPPO and an increase observed for TSPO1. The two passivating molecules resulted in differences in energy-level alignment, electron injection, film morphology and crystallinity, and ion migration during operation. While TPPO resulted in improved photoluminescence decay times, overall higher maximum external quantum efficiency (EQE) and device lifetime were obtained for TSPO1 compared to TPPO (14.4% vs 12.4% EQE, 341 min vs 42 min T50).

Construction of the first high-density genetic linkage map and QTL mapping of flavonoid and leaf-size related traits in Epimedium.

BACKGROUND: Leaves are the main medicinal organ in Epimedium herbs, and leaf flavonoid content is an important criterion of Epimedium herbs. However, the underlying genes that regulate leaf size and flavonoid content are unclear, which limits the use of breeding for Epimedium development. This study focuses on QTL mapping of flavonoid and leaf-size related traits in Epimedium. RESULTS: We constructed the first high-density genetic map (HDGM) using 109 F1 hybrids of Epimedium leptorrhizum and Epimedium sagittatum over three years (2019-2021). Using 5,271 single nucleotide polymorphism (SNP) markers, an HDGM with an overall distance of 2,366.07 cM and a mean gap of 0.612 cM was generated by utilizing genotyping by sequencing (GBS) technology. Every year for three years, 46 stable quantitative trait loci (QTLs) for leaf size and flavonoid contents were discovered, including 31 stable loci for Epimedin C (EC), one stable locus for total flavone content (TFC), 12 stable loci for leaf length (LL), and two stable loci for leaf area (LA). For flavonoid content and leaf size, the phenotypic variance explained for these loci varied between 4.00 and 16.80% and 14.95 and 17.34%, respectively. CONCLUSIONS: Forty-six stable QTLs for leaf size and flavonoid content traits were repeatedly detected over three years. The HDGM and stable QTLs are laying the basis for breeding and gene investigation in Epimedium and will contribute to accelerating the identification of desirable genotypes for Epimedium breeding.

Dietary supplementation with jasmine flower residue improves meat quality and flavor of goat.

Jasmine flower residue (JFR) is a by-product retained in the production process of jasmine tea and can be used as an unconventional feed due to its rich nutrient value. This study aimed to evaluate the effects of the addition of JFR to the diet of goats on their meat quality and flavor. Twenty-four castrated Nubian male goats were randomly divided into two groups and fed a mixed diet containing 10% JFR (JFR, n = 12) or a conventional diet (CON, n = 12) for 45 days. Meat quality and flavor were measured at the end of the treatment. The addition of JFR to the diet could reduce the shear force of the longissimus dorsi muscle, as well as, the cross-sectional area and diameter of muscle fibers, indicating that the addition of JFR improved meat quality. JFR also increased the content of glutamic acid and ω-3 polyunsaturated fatty acid (C18:3n3 and C20:5N3) and reduced the content of C24:1 and saturated fatty acid (C20:0 and C22:0). In addition, the use of JFR increased the content of acetaldehyde and hexanal in the meat. Furthermore, JFR introduced new volatile components in the meat. The umami, saltiness, and richness of the meat also improved. In conclusion, the addition of jasmine flower residue to the diet can improve the meat quality and flavor of goat.

Capillary-in-Capillary Electrospray Ionization (CC-ESI) Source Enabling Convenient Sampling and Quantitative Analysis for Point-of-Care Testing.

With outstanding analytical performances, mass spectrometry (MS) has shown great potential for clinical applications. To facilitate the sampling process and quantitative analysis, a capillary-in-capillary electrospray ionization (CC-ESI) source was developed in this study. Utilizing two nested capillaries as a sampler and an ESI emitter, the source enabled spontaneous liquid sampling based on the capillary phenomenon and electrospray ionization mass spectrometry (ESI-MS) analysis. Apart from the cheap price, high portability, and disposability, the CC-ESI had merits of quantitation capability as well as adequate sensitivity. By coupling CC-ESI to a miniature mass spectrometer (mini-MS), a limit of detection (LOD) of 1 ng/mL was achieved for standard imatinib at collision-induced dissociation (CID) tandem MS mode, and a LOQ of 1 ng/mL was obtained for atenolol and imatinib (with isotopic internal standard) at multiple ion reaction monitoring (MRM) modes. As two demonstrations for analysis of practical samples, rapid analysis of abused drugs on surface and quantitative analysis of therapeutic drugs in whole blood were also performed with a CC-ESI mini-MS.

[Review of classical prescriptions in treatment of ulcerative colitis].

Ulcerative colitis(UC) is a continuous inflammatory bowel disease with the main clinical manifestations of abdominal pain, diarrhea, and mucous bloody stools, mainly attacking the colorectal mucosa and submucosa. It is characterized by high recurrence rate, difficult cure, and clustering and regional occurrence. Chinese medicinal prescriptions for the treatment of UC have good therapeutic effect, multi-target regulation, slight toxicity, and no obvious side effects. In particular, the classical prescriptions highlight the characteristics and advantages of traditional Chinese medicine theory and have attracted much attention in recent years. To enable researchers to timely and comprehensively understand the classical prescriptions in the treatment of UC, we reviewed the studies about the pharmacodynamic material basis, quality control, action mechanism, and clinical application of relevant classical prescriptions. We first introduced the latest research progress in the active components such as alkaloids, polysaccharides, saponins, and flavonoids in relevant classical prescriptions. Then, we reviewed the latest research achievements on the quality control of classical prescriptions for the treatment of UC by gas chromatography, liquid chromatography, mass spectrometry, liquid chromatography-mass spectrometry and the like. Further, we summarized the research advances in the mechanisms of relevant prescriptions in the treatment of UC based on network pharmacology, molecular docking, integrated pharmacology platform, and animal experiments. Finally, we generalized the clinical application of the classical prescriptions for clearing heat and removing dampness, mildly regulating cold and heat, soothing liver and regulating spleen, strengthening spleen and invigorating Qi, and tonifying spleen and stomach. By systematic summary of the research progress in relevant classical prescriptions, we hope to promote the application and development of such prescriptions in UC treatment.

Differential diagnosis of Crohn's disease and intestinal tuberculosis: development and assessment of a nomogram prediction model.

BACKGROUND: China is a region with a high incidence of tuberculosis, and the incidence of IBD has also been rising rapidly in recent years. Differentiating Crohn's disease(CD) from intestinal tuberculosis (ITB) has become a very challenging issue. We aimed to develop and assess a diagnostic nomogram to differentiate between CD and ITB to improve the accuracy and practicability of the model. METHODS: A total of 133 patients (CD 90 and ITB 43) were analyzed retrospectively. Univariate and multivariate logistic regression analysis was included to determine the independent predictive factors and establish the regression equation. On this basis, the nomogram prediction model was constructed. The discrimination, calibration and clinical efficiency of the nomogram were assessed using area under the curve(AUC), C-index, calibration curve, decision curve analysis (DCA) and clinical impact curve. RESULTS: T-SPOT positive, cobblestone appearance, comb sign and granuloma were significant predictors in differentiating CD from ITB. Base on the above independent predictors, a diagnostic nomogram was successfully established. The sensitivity, specificity, accuracy of the prediction model are 94.4%, 93.0%, 94.0% respectively. The AUC and the C-index of the prediction model are both 0.988, which suggest that the model had a good discrimination power. The calibration curve indicated a high calibration degree of the prediction model. The DCA and clinical impact curve indicated a good clinical efficiency of the prediction model which could bring clinical benefits. CONCLUSION: A nomogram prediction model for distinguishing CD from ITB was developed and assessed, with high discrimination, calibration and clinical efficiency. It can be used as an accurate and convenient diagnostic tool to distinguish CD from ITB, facilitating clinical decision-making.

Solvent-Modulated Self-Assembly of Naphthalenediimide-Based Cd(II) Complexes and the Controllable Photochromism via Conformational Isomerization.

Rational regulation of the properties of photochromic materials is a challenging and meaningful work. In the present work, NDI-based complexes, namely, [Cd0.5(NDI)(HBDC)]·H2O (1) and a series of conformational isomers of {[Cd(NDI)0.5(BDC)]·MeCN}n (2), were synthesized by varying the solvent conditions (H2BDC = terephthalic acid, NDI = N,N'-bis(3-pyridylcarbonylhydrazine)-1,4,5,8-naphthalene diimide). Complex 1 exhibits a 0D mononuclear structure without photochromic behavior due to the bad conjugation of the naphthalene diimide moiety. The conformational isomers of complex 2 manifest a 3D network, showing ultra-fast photo-induced intermolecular electron transfer photochromic behavior under X-ray, UV, and visible light. However, they show different photochromic rates and coloring contrast upon photoirradiation, which originates from their difference in the distances of lone pair(COO)···π(NDI). This was realized via controlling the solvent ratio in the reaction system. In addition, compared to UV/X-ray light, 2 exhibits greater sensitivity to visible light and is an organic-inorganic hybrid material with photomodulated luminescence. Based on the excellent performance, complex 2 can be applied to filter paper, showing potential applications as an inkless printing medium and selective perception of ammonia and amine vapors in the solid state via different visual color changes.

Taxonomy of Epimedium (Berberidaceae) with special reference to Chinese species.

Epimedii Herba is a commonly used traditional Chinese herbal medicine. Five Epimedium species are included in Chinese Pharmacopoeia and most species of Epimedium are used as Epimedii Herba in practical application. However, as the largest herbaceous genus of the Berberidaceae, Epimedium has many taxonomic controversies which hinder the effective use of Epimedii Herba. This paper reviewed the taxonomic research related to Epimedium, including taxonomic history, taxonomic values of morphological characters, species and distribution, infra-genera taxonomic system and the taxonomic research of Chinese Epimedium. For instance, we recognized Epimedium wushanense and clarified that the species, as described in Flora Reipublicae Popularis Sinicae and Flora of China, actually includes four Epimedium species similar in leaflet shape. In general, it was recognized here that Epimedium comprises 62 species, of which 52 species are distributed in China. For Chinese Epimedium species with the most taxonomic problems, the taxonomic research on the taxa was reviewed and the newest species key was proposed along with proposals for those taxonomic problems needing further resolution. This review is of great implication for the identification, exploration and utilization of Epimedii Herba.

Diammonium-Mediated Perovskite Film Formation for High-Luminescence Red Perovskite Light-Emitting Diodes.

3D mixed-halide perovskite-based red emitters combine excellent charge-transport characteristics with simple solution processing and good film formation; however, light-emitting diodes (LEDs) based on these emitters cannot yet outperform their nanocrystal counterparts. Here the use of diammonium halides in regulating the formation of mixed bromide-iodide perovskite films is explored. It is found that the diammonium cations preferentially bond to Pb-Br, rather than Pb-I, octahedra, promoting the formation of quasi-2D phases. It is proposed that the perovskite formation is initially dominated by the crystallization of the thermodynamically more favorable 3D phase, but, as the solution gets depleted from the regular A cations, thin shells of amorphous quasi-2D perovskites form. This leads to crystalline perovskite grains with efficiently passivated surfaces and reduced lattice strain. As a result, the diammonium-treated perovskite LEDs demonstrate a record luminance (10745 cd m-2 ) and half-lifetime among 3D perovskite-based red LEDs.

Neuroendocrine-Immune Regulatory Network of Eucommia ulmoides Oliver.

Eucommia ulmoides Oliver (E. ulmoides) is a popular medicinal herb and health supplement in China, Japan, and Korea, and has a variety of pharmaceutical properties. The neuroendocrine-immune (NEI) network is crucial in maintaining homeostasis and physical or psychological functions at a holistic level, consistent with the regulatory theory of natural medicine. This review aims to systematically summarize the chemical compositions, biological roles, and pharmacological properties of E. ulmoides to build a bridge between it and NEI-associated diseases and to provide a perspective for the development of its new clinical applications. After a review of the literature, we found that E. ulmoides has effects on NEI-related diseases including cancer, neurodegenerative disease, hyperlipidemia, osteoporosis, insomnia, hypertension, diabetes mellitus, and obesity. However, clinical studies on E. ulmoides were scarce. In addition, E. ulmoides derivatives are diverse in China, and they are mainly used to enhance immunity, improve hepatic damage, strengthen bones, and lower blood pressure. Through network pharmacological analysis, we uncovered the possibility that E. ulmoides is involved in functional interactions with cancer development, insulin resistance, NAFLD, and various inflammatory pathways associated with NEI diseases. Overall, this review suggests that E. ulmoides has a wide range of applications for NEI-related diseases and provides a direction for its future research and development.

HPLC-PDA-Guided isolation of glucosyloxybenzyl 2-isobutylmalates from the pseudobulbs of Bletilla striata with neuroprotective and antimicrobial activities.

Twelve undescribed glucosyloxybenzyl 2-isobutylmalates, bletistrosides A-L were obtained from the pseudobulbs of Bletilla striata under the guidance of HPLC-PDA. Their structures and absolute configurations were determined by the spectroscopic analyses, along with acidic hydrolysis and alkaline hydrolysis experiments. The neuroprotective effects and the antimicrobial activities of selective compounds were evaluated. Bletistroside G exhibited potential neuroprotective effect against glutamate-induced PC12 cell injury, with improving cell viabilities by 11.24% compared to the model group at 10 µM. Bletistrosides A, B, G, and L showed weak antimicrobial activities against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, however, bletistroside G showed obviously selective inhibition against P. aeruginosa.