Umbilical cord mesenchymal stem cell-derived exosomes inhibits fibrosis in human endometrial stromal cells via miR-140-3p/FOXP1/Smad axis.

Endometrial fibrosis is the histologic appearance of intrauterine adhesion (IUA). Emerging evidences demonstrated umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-exo) could alleviate endometrial fibrosis. But the specific mechanism is not clear. In this study, we explored the effect of UCMSC-exo on endometrial fibrosis, and investigated the possible role of miR-140-3p/FOXP1/Smad axis in anti-fibrotic properties of UCMSC-exo. UCMSC-exo were isolated and identified. Transforming growth factor-ß (TGF-ß) was used to induce human endometrial stromal cell (HESC) fibrosis. Dual luciferase assay was performed to verify the relationship between miR-140-3p and FOXP1. The expressions of fibrotic markers, SIP1, and p-Smad2/p-Smad3 in HESCs stimulated with UCMSC-exo were detected by western blot. In addition, the effects of miR-140-3p mimic, miR-140-3p inhibitor and FOXP1 over-expression on endometrial fibrosis were assessed. The isolated UCMSC-exo had a typical cup-shaped morphology and could be internalized into HESCs. The expressions of fibrotic markers were significantly increased by TGF-ß, which was reversed by UCMSC-exo. MiR-140-3p in UCMSC-exo ameliorated TGf-ß-induced HESCs fibrosis. FOXP1 was identified as the direct target of miR-140-3p, which could inversely regulate miR-140-3p's function on HESCs fibrosis. Furthermore, we demonstrated that miR-140-3p in UCMSC-exo regulated Smad signal pathway to exert the anti-fibrotic effect in HESCs. The anti-fibrotic effect of UCMSC-derived exosomes against HESC fibrosis was at least partially achieved by miR-140-3p/FOXP1/Smad axis.

Molecular and Heterojunction Device Engineering of Solution-Processed Conjugated Reticular Oligomers: Enhanced Photoelectrochemical Hydrogen Evolution through High-Effective Exciton Separation.

Covalent organic frameworks (COFs) face limited processability challenges as photoelectrodes in photoelectrochemical water reduction. Herein, sub-10 nm benzothiazole-based colloidal conjugated reticular oligomers (CROs) are synthesized using an aqueous nanoreactor approach, and the end-capping molecular strategy to engineer electron-deficient units onto the periphery of a CRO nanocrystalline lattices (named CROs-Cg). This results in stable and processable "electronic inks" for flexible photoelectrodes. CRO-BtzTp-Cg and CRO-TtzTp-Cg expand the absorption spectrum into the infrared region and improve fluorescence lifetimes. Heterojunction device engineering is used to develop interlayer heterojunction and bulk heterojunction (BHJ) photoelectrodes with a hole transport layer, electron transport layer, and the main active layers, using a CROs/CROs-Cg or one-dimensional (1D) electron-donating polymer HP18 mixed solution via spinning coating. The ITO/CuI/CRO-TtzTp-Cg-HP18/SnO2 /Pt photoelectrode shows a photocurrent of 94.9 µA cm-2 at 0.4 V versus reversible hydrogen electrode (RHE), which is 47.5 times higher than that of ITO/Bulk-TtzTp. Density functional theory calculations show reduced energy barriers for generating adsorbed H* intermediates and increased electron affinity in CROs-Cg. Mott-Schottky and charge density difference analyses indicate enhanced charge carrier densities and accelerated charge transfer kinetics in BHJ devices. This study lays the groundwork for large-scale production of COF nanomembranes and heterojunction structures, offering the potential for cost-effective, printable energy systems.

Mangiferin, a Potential Supplement to Improve Metabolic Syndrome: Current Status and Future Opportunities.

Metabolic syndrome (MetS) represents a considerable clinical and public health burden worldwide. Mangiferin (MF), a flavonoid compound present in diverse species such as mango (Mangifera indica L.), papaya (Pseudocydonia sinensis (Thouin) C. K. Schneid.), zhimu (Anemarrhena asphodeloides Bunge), and honeybush tea (Cyclopia genistoides), boasts a broad array of pharmacological effects. It holds promising uses in nutritionally and functionally targeted foods, particularly concerning MetS treatment. It is therefore pivotal to systematically investigate MF's therapeutic mechanism for MetS and its applications in food and pharmaceutical sectors. This review, with the aid of a network pharmacology approach complemented by this experimental studies, unravels possible mechanisms underlying MF's MetS treatment. Network pharmacology results suggest that MF treats MetS effectively through promoting insulin secretion, targeting obesity and inflammation, alleviating insulin resistance (IR), and mainly operating via the phosphatidylinositol 3 kinase (PI3K)/Akt, nuclear factor kappa-B (NF-[Formula: see text]B), microtubule-associated protein kinase (MAPK), and oxidative stress signaling pathways while repairing damaged insulin signaling. These insights provide a comprehensive framework to understand MF's potential mechanisms in treating MetS. These, however, warrant further experimental validation. Moreover, molecular docking techniques confirmed the plausibility of the predicted outcomes. Hereafter, these findings might form the theoretical bedrock for prospective research into MF's therapeutic potential in MetS therapy.

Comprehensive Analysis of Bufadienolide and Protein Profiles of Gland Secretions from Medicinal Bufo Species.

Toad Venom (TV) is the dried product of toxic secretions from Bufo bufo gargarizans Cantor (BgC) or B. melanostictus Schneider (BmS). Given the increasing medical demand and the severe depletion of wild toads, a number of counterfeit TVs appeared on the market, posing challenges to its quality control. In order to develop an efficient, feasible, and comprehensive approach to evaluate TV quality, a thorough analysis and comparison of chemical compounds among legal species BgC and BmS, as well as the main confusion species B. andrewsi Schmidt (BaS) and B. raddei Strauch (BrS), were conducted by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), high performance liquid chromatography (HPLC), sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and Nano LC-MS/MS analyses. We identified 126 compounds, including free or conjugated bufadienolides, indole alkaloids and amino acids, among the four Bufo species. The content of main bufadienolides, such as gamabufotalin, bufotalin, bufalin, cinobufagin, and resibufogenin, and the total protein contents varied widely among 28 batches of TV due to their origin species. The sum of the five bufadienolides within the BgC, BmS, BaS, and BrS samples were 8.15-15.93%, 2.45-4.14%, 11.15-13.50%, and 13.21-14.68%, respectively. The total protein content of BgC (6.9-24.4%) and BaS (19.1-20.6%) samples were higher than that of BmS (4.8-20.4%) and BrS (10.1-13.7%) samples. Additionally, a total of 1357 proteins were identified. There were differences between the protein compositions among the samples of the four Bufo species. The results indicated that BgC TV is of the highest quality; BaS and BrS TV could serve as alternative resources, whereas BmS TV performed poorly overall. This research provides evidence for developing approaches to evaluate TV quality and selecting the proper Bufo species as the origin source of TV listed in the Chinese pharmacopoeia.

Analysis of factors associated with needlestick injuries of clinical nurses by applying a human factor analysis and classification system: A nationwide cross-sectional survey.

AIMS: This study aims to investigate the current situation of needlestick injuries (NSIs) of clinical nurses and identify associated factors by using the theoretical framework of the human factors analysis and classification system (HFACS). DESIGN: A nationwide cross-sectional survey was conducted. METHODS: Multi-stage sampling was used to investigate 3336 nurses in 14 Chinese hospitals. Descriptive statistics and univariate and multivariate logistic regression were employed to reveal the rate of NSIs and their associated factors. RESULTS: A total of 970 nurses (29.1%) reported having experienced at least one NSI in the past year. The multivariate logistic regression analysis showed that good hospital safety climate and clinical nurses in intensive care unit (ICU) and emergency department had protective effects against NSIs compared with nurses in internal medicine department. The nurse, senior nurse, and nurse in charge have significantly increased the risk for NSIs compared with the associate chief nurse or above. Patients with poor vision but wearing glasses and poor vision but not wearing glasses were more prone to have NSIs. Working in the operating room compared with internal medicine, average weekly working time of >45 h compared with ≤40 h and poor general health led to increased risk of NSIs. CONCLUSION: The rate of NSIs in clinical nurses was high in China. Individual factors including professional title, department, visual acuity and general mental health and organisational factors including weekly working hours and hospital safety atmosphere were significantly correlated with the occurrence of NSIs. RELEVANCE TO CLINICAL PRACTICE: Nursing managers should focused on physical and psychological conditions of clinical nurses, and organisational support is required to enhance the hospital safety atmosphere. NO PATIENT OR PUBLIC CONTRIBUTION: Contributions from patients or the public are irrelevant because this study aims to explore current situation and factors associated with NSIs in clinical nurses.

Identification and genetic characterization of a novel species of Choleoeimeria Schneider, 1875 from a captive-bred bilby (Thylacomyidae; Macrotis lagotis) (Reid, 1837) in Western Australia.

A novel Eimeria sp. from a captive-bred bilby (Macrotis lagotis Reid, 1837) has been identified in Western Australia. The bilby was bred at the Kanyana Wildlife Rehabilitation Centre, Perth, as part of the National Bilby Recovery Plan. Oocysts (n = 31) irregular blunt ellipsoidal, 17-18 × 11-12 (17.2 × 11.3); length/width (L/W) ratio 1.4-1.5 (1.5). Wall bi-layered, 0.8-1.0 (0.9) thick, outer layer smooth, c.2/3 of total thickness. Micropyle barely discernible. Oocyst residuum is absent, but 2-3 small polar granules are present. Sporocysts (n = 31) ovoidal, 7-8 × 5-6 (7.8 × 5.7); L/W ratio 1.3-1.4 (1.4). Stieda, sub-Stieda and para-Stieda bodies absent or indiscernible; sporocyst residuum present, usually as an irregular body consisting of numerous granules that appear to be membrane-bound or sometimes diffuse among sporozoites. Sporozoites vermiform with a robust refractile body. Further molecular characterization was conducted on the sporulated oocysts. At the 18S locus, it sat in a large clade of the phylogenetic tree with two isolates of Eimeria angustus from quendas (Isoodon obesulus Shaw, 1797) and the Choleoeimeria spp. It shared the highest identity with E. angustus (KU248093) at 98.84%; at the COI gene locus, it was unique and most closely related to Choleoeimeria taggarti, which is hosted by another species of marsupial, the yellow-footed antechinus (Antechinus flavipes flavipes), with 90.58% genetic similarity. Based on morphological and molecular data, this isolate is a new species and named as Choleoeimeria yangi n. sp.

Fingerprint analysis of dang-gui-Si-Ni decoction and its anticoagulant activity in vivo-in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Dang-Gui-Si-Ni (DGSN) decoction is a classic prescription in the clinical practice of traditional Chinese Medicine (TCM). DGSN decoction is often used to relieve symptoms of cold coagulation and blood stasis recorded by Treatise on Febrile Diseases (Shang Han Lun) and treat Raynaud's disease, dysmenorrhea, arthritis, migraine in TCM clinic. Accumulated evidences have suggested that this diseases are related to microcirculation disturbance. However, the anticoagulant activity and underlying mechanisms of DGSN decoction responsible for the therapeutic not well understood. AIM OF THE STUDY: The fingerprint and anticoagulant activity in vivo-in vitro of DGSN decoction were evaluated to strengthen the quality control and activity study of formulas. MATERIALS AND METHODS: The chemical components of DGSN decoction were analyzed by HPLC and its fingerprint similarity were evaluated by "Chinese Medicine Chromatographic Fingerprint Similarity Evaluation Software (2012 Edition)". The anticoagulant activity of DGSN decoction was assessed by measuring four coagulation factors (PT, TT, APTT, FIB) in vitro. Zebrafish thrombosis model induced by punatinib was established to evaluate the activity of improving microvascular hemodynamics in vivo. Quantitative real-time polymerase chain reaction (q-PCR) were adopted to compare the changes in the RNA expression levels of coagulation factor II (FII), VII (FVII), IX (FIX) and X (FX) in zebrafish thrombosis model. RESULTS: The fingerprint similarity evaluation method of DGSN decoction was established. The results showed that 18 samples had higher similarity (S1-S18 > 0.878). Pharmacodynamic results showed that DGSN decoction could extend PT, TT and APTT, and reduce FIB content in vitro. Meanwhile, it markedly enhanced the cardiac output and blood flow velocity at low dosage (500 µg mL-1) in vivo. q-PCR data demonstrated that DGSN decoction (500 µg mL-1) could downregulate the RNA expression of FII, FVII, FIX and FX. Interestingly, there were a bidirectional regulation of FII, FIX and FX in a certain concentration range. In general, DGSN decoction can significantly improve hemodynamics and downregulate coagulation factors, and the results were consistent both in vitro - in vivo. CONCLUSION: The fingerprint study provide a new perspective for improving the quality control of DGSN decoction. DGSN decoction possess anticoagulant activity by regulating multiple coagulation factors simultaneously. Thus, it has the potential to develop into the novel raw material of anticoagulant drugs.

Steroidal saponins from rhizome of Paris polyphylla var. chinensis and their anti-inflammatory, cytotoxic effects.

Five undescribed compounds, including two cholestane glycosides parispolyosides A and E, and three spirostanol glycosides parispolyosides B-D, were isolated from rhizome of Paris polyphylla var. chinensis (Franch.) Hara, together with twenty-one known steroidal saponins. Their chemical structures were elucidated on the basis of comprehensive analysis of 1D and 2D NMR, as well as HR-ESI-MS spectroscopic data. Two of these compounds demonstrated potent inhibitory effect on NO production stimulated by lipopolysaccharide in raw 264.7 cells with IC50 values of 61.35 µM and 37.23 µM. Four compounds exhibited moderate inhibitory activity against HepG2 cells with IC50 values ranging from 9.43 to 24.54 µM. Molecular docking analysis revealed that the potential mechanism of NO inhibition by the active compounds was associated with the interactions with iNOS protein.

Antibacterial and antioxidant activities of a novel biosynthesized selenium nanoparticles using Rosa roxburghii extract and chitosan: Preparation, characterization, properties, and mechanisms.

Developing efficient and safe antibacterial agents to inhibit pathogens including Physalospora piricola and Staphylococcus aureus is of great importance. Herein, a novel compound composed of Rosa roxburghii procyanidin, chitosan and selenium nanoparticle (RC-SeNP) was bio-synthesized, with the average diameter and zeta potential being 84.56 nm and -25.60 mV, respectively. The inhibition diameter of the RC-SeNP against P. piricola and S. aureus reached 18.67 mm and 13.13 mm, and the maximum scavenging activity against DPPH and ABTS reached 96.02% and 98.92%, respectively. Moreover, the RC-SeNP completely inhibited the propagation P. piricola and S. aureus on actual apples, suggesting excellent in vivo antimicrobial capacity. The transcriptome analysis and electron microscope observation indicated that the antibacterial activity would be attributed to adhering to and crack the cell walls as well as damage the cytomembrane and nucleus. Moreover, the RC-SeNP effectively maintained the vitamin C, total acid, and water contents of red bayberry, demonstrating potential application for fruit preservation. At last, the RC-SeNP showed no cell toxicity and trace selenium residual dose (0.03 mg/kg on apple, 0.12 mg/kg on red bayberry). This study would enlighten future development on novel nano-bioantibacterial agents for sustainable agriculture.

Comprehensive insight into the pharmacology, pharmacokinetics, toxicity, detoxification and extraction of hypaconitine from Aconitum plants.

ETHNOPHARMACOLOGICAL RELEVANCE: Hypaconitine (HA), a diterpenoid alkaloid, mainly derived from Aconitum plants such as Acoitum carmichaeli Debx. And Aconitum nagarum Stapf., has recently piqued significant interest among the scientific community given its multifaceted attributes including anti-inflammatory, anticancer, analgesic, and cardio-protective properties. AIM OF THE STUDY: This review presents a comprehensive exploration of the research advancements regarding the traditional uses, pharmacology, pharmacokinetics, toxicity, and toxicity reduction of HA. It aims to provide a thorough understanding of HA's multifaceted properties and its potential applications in various fields. MATERIALS AND METHODS: A systematic literature search was conducted using several prominent databases including PubMed, Web of Science, NCBI, and CNKI. The search was performed using specific keywords such as "hypaconitine," "heart failure," "anti-inflammatory," "aconite decoction," "pharmacological," "pharmacokinetics," "toxicity," "detoxification or toxicity reduction," and "extraction and isolation." The inclusion of these keywords ensured a comprehensive exploration of relevant studies and enabled the retrieval of valuable information pertaining to the various aspects of HA. RESULTS: Existing research has firmly established that HA possesses a range of pharmacological effects, encompassing anti-cardiac failure, anti-inflammatory, analgesic, and anti-tumor properties. The therapeutic potential of HA is promising, with potential applications in heart failure, ulcerative colitis, cancer, and other diseases. Pharmacokinetic studies suggest that HA exhibits high absorption rates, broad distribution, and rapid metabolism. However, toxic effects of HA on the nerves, heart, and embryos have also been observed. To mitigate these risks, HA needs attenuation before use, with the most common detoxification methods being processing and combined use with other drugs. Extraction methods for HA most commonly include cold maceration, soxhlet reflux extraction, and ultrasonic-assisted extraction. Despite the potential therapeutic benefits of HA, further research is warranted to elucidate its anti-heart failure effects, particularly in vivo, exploring aspects such as in vivo metabolism, distribution, and metabolites. Additionally, the therapeutic effects of HA monomers on inflammation-induced diseases and tumors should be validated in a more diverse range of experimental models, while the mechanisms underlying the therapeutic effects of HA should be investigated in greater detail. CONCLUSION: This review serves to emphasize the therapeutic potential of HA and highlights the crucial need to address its toxicity concerns before considering clinical application. Further research is required to comprehensively investigate the pharmacological properties of HA, with particular emphasis on its anti-cardiac failure and anti-inflammatory activities. Such research endeavors have the potential to unveil novel treatment avenues for a broad spectrum of diseases.

Damage mechanism and therapy progress of the blood-brain barrier after ischemic stroke.

The blood-brain barrier (BBB) serves as a defensive line protecting the central nervous system, while also maintaining micro-environment homeostasis and inhibiting harmful materials from the peripheral blood. However, the BBB's unique physiological functions and properties make drug delivery challenging for patients with central nervous system diseases. In this article, we briefly describe the cell structure basis and mechanism of action of the BBB, as well as related functional proteins involved. Additionally, we discuss the various mechanisms of BBB damage following the onset of an ischemic stroke, and lastly, we mention several therapeutic strategies accounting for impairment mechanisms. We hope to provide innovative ideas for drug delivery research via the BBB.

Biomedical Application of Decellularized Scaffolds.

Tissue loss and end-stage organ failure are serious health problems across the world. Natural and synthetic polymer scaffold material based artificial organs play an important role in the field of tissue engineering and organ regeneration, but they are not from the body and may cause side effects such as rejection. In recent years, the biomimetic decellularized scaffold based materials have drawn great attention in the tissue engineering field for their good biocompatibility, easy modification, and excellent organism adaptability. Therefore, in this review, we comprehensively summarize the application of decellularized scaffolds in tissue engineering and biomedicine in recent years. The preparation methods, modification strategies, construction of artificial tissues, and application in biomedical applications are discussed. We hope that this review will provide a useful reference for research on decellularized scaffolds and promote their application tissue engineering.

[Research progress in quality control of Bufonis Venenum in preparations].

Bufonis Venenum, an animal medicinal material, is widely used for treating cardiovascular diseases and pain induced by rheumatics or malignant tumors. In view of the high activity and high toxicity, it is of great significance to pay attention to the quality control of Bufonis Venenum to ensure the safety and effectiveness of its preparations. China's drug standards involve 102 preparations(474 batch numbers) containing Bufonis Venenum approved for sale, including 14 preparations in the Chinese Pharmacopoeia(2020 edition) and 68 preparations in the standards issued by the Ministry of Health Drug Standard of the People's Republic of China. Bufonis Venenum is mostly used in pill and powder preparations in the form of raw powder, with the main functions of clearing heat, removing toxin, relieving swelling and pain, replenishing qi, activating blood, opening orifice, and awakening brain. Except the high level of quality control for Bufonis Venenum in the preparations in the Chinese Pharmacopoeia(2020 edition), the quality control standards of Bufonis Venenum in other preparations are low or even absent. Therefore, it is urgent to conduct research on the improvement of quality standards for the preparations containing Bufonis Venenum. This study retrieved the reports focusing on the quality evaluation and quality control of the preparations containing Bufonis Venenum from CNKI, PubMed, and Web of Science. Qualitative and quantitative analysis methods for 64 preparations containing Bufonis Venenum have been reported, mainly including thin-layer chromatography, HPLC fingerprint, and multi-component content determination. The index components mainly involved bufadienolides, such as gamabufalin, arenobufagin, bufotalin, bufalin, cinobufagin, and resibufogenin. According to the literature information, this paper suggests that attention should be paid to the correlations between the analysis methods and detection indexes of medicinal materials, decoction pieces and preparations, the monitoring of indole alkaloids, and the content uniformity inspection for further improving the quality standards for the preparations containing Bufonis Venenum.

[Chemical composition and antioxidant activity of different parts of Prunella vulgaris by UPLC-Q-TOF-MS/MS and UPLC].

Prunellae Spica is the dried spica of Prunella vulgaris belonging to Labiatae and it is widely used in pharmaceutical and general health fields. As a traditional Chinese medicine cultivated on a large scale, it produces a large amount of non-medicinal parts, which are discarded because they are not effectively used. To analyze the chemical constituents in the different samples from spica, seed, stem, and leaf of P. vulgaris, and explore the application value and development prospect of these parts, this study used ultrahigh performance liquid chromatography-tandem quadrupoles time of flight mass spectrometry(UPLC-Q-TOF-MS/MS) to detect chemical constituents in different parts of P. vulgaris. As a result, 117 compounds were detected. Among them, 87 compounds were identified, including 32 phenolic acids, 8 flavonoids, and 45 triterpenoid saponins. Some new triterpenoid saponins containing the sugar chain with 4-6 sugar units were found. Further, multivariate statistical analysis was conducted on BPI chromatographic peaks of multiple batches of different parts, and the results showed that spica had the most abundant chemical constituents, including salviaflaside and linolenic acid highly contained in the seed and phenolic acids, flavonoids, and triterpenoid saponins in the stem and leaf. In general, the constituents in the spica were composed of those in the seed, stem, and leaf. UPLC was used to determine the content of 6 phenolic acids(danshensu, protocatechuic acid, protocatechuic aldehyde, caffeic acid, salviaflaside, and rosmarinic acid) in different parts. The content of other phenolic acids in the seed was generally lower than that in the spica except that of salviaflaside. The content of salviaflaside in the spica was higher than that in the stem and leaf, but the content of other phenolic acids in the spica was not significantly different from that in the stem. The content of protocatechuic aldehyde and caffeic acid in the spica was lower than that in the leaf. DPPH free radical scavenging method was used to detect the antioxidant activity of four parts, and there was no significant difference in the antioxidant activity between the spica and the stem and leaf, but that was significantly higher than the seed. Moreover, the antioxidant activity of these parts was correlated with the content of total phenolic acids. Based on the above findings, the stem and leaf of P. vulgaris have potential application value. Considering the traditional medication rule, it is feasible to use the whole plant as a medicine. Alternatively, salviaflaside, occurring in the seed, can be used as a marker compound for the quality evaluation of Prunellae Spica, if only using spica as the medicinal part of P. vulgaris, as described in the Chinese Pharmacopoeia(2020 edition).

[New steroidal saponins from aerial parts of Paris polyphylla var. chinensis].

The shortage of Paridis Rhizoma promotes comprehensive utilization and development research of waste aerial parts of the original plant. The chemical compositions of the aerial parts of Paris polyphylla var. chinensis were clarified based on the ultrahigh performance liquid chromatography tandem quadrupoles time of flight mass spectrometry(UPLC-QTOF-MS/MS) in the previous investigation, and a series of flavonoids and steroidal saponins were isolated. The present study continued the isolation and structure identification of the new potential compounds discovered based on UPLC-QTOF-MS/MS. By using silica gel, ODS, flash rapid preparation, and other column chromatography techniques, combined with prepared high performance liquid chromatography, five compounds were isolated from the 75% ethanol extract of the aerial parts of P. polyphylla var. chinensis, and their structures were identified by spectral data combined with chemical transformations, respectively, as(23S,25R)-23,27-dihydroxy-diosgenin-3-O-α-L-rhamnopyranosyl-(1→2)-[ß-D-glucopyranosyl-(1→3)]-ß-D-glucopyranoside(1),(25R)-26-O-ß-D-glucopyranosyl-furost-5-en-3ß,22α,26-triol-3-O-α-L-rhamnopyranosyl-(1→2)-[ß-D-glucopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→4)]-ß-D-glucopyranoside(2),(25R)-27-O-ß-D-glucopyranosyl-5-en-3ß,27-dihydroxyspirost-3-O-α-L-rhamnopyranosyl-(1→2)-[ß-D-glucopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→4)]-ß-D-glucopyranoside(3),(25R)-27-O-ß-D-glucopyranosyl-5-en-3ß,27-dihydroxyspirost-3-O-α-L-rhamnopyranosyl-(1→2)-[ß-D-glucopyranosyl-(1→3)]-ß-D-glucopyranoside(4), and aculeatiside A(5). Among them, compounds 1-4 were new ones, and compound 5 was isolated from P. polyphylla var. chinensis for the first time.

[Discovery, isolation and structural identification of alkaloid glycosides in six traditional Chinese medicine such as Coptis chinensis].

Alkaloids are important active ingredients occurring in many traditional Chinese medicines, and alkaloid glycosides are one of their existence forms. The introduction of saccharide units improves the water solubility of alkaloid glycosides thus presenting better biological activity.Because of the low content in plants, alkaloid glycosides have been not comprehensively studied. In this study, ultrahigh performance liquid chromatography-quadrupole time of flight-tandem mass spectrometry(UPLC-QTOF-MS/MS) was employed to identify and analyze the alkaloid glycosides in Coptis chinensis, Phellodendron chinense, Menispermum dauricum, Sinomenium acutum, Tinospora sagittata and Stephania tetrandra. The results showed that except Tinospora sagittata, the other five herbal medicines contained alkaloid glycosides. Furthermore, the alkaloid glycosides in each herbal medicine were identified based on UV absorption spectra, quasimolecular ion peaks in MS, fragment ions information in the MS/MS, and previous literature reports. A total of 42 alkaloid glycosides were identified. More alkaloid glycosides were identified in C. chinensis and Menispermum dauricum, and eleven in C. chinensis were potential new compounds. Furthermore, the alkaloid glycosides in the water extract of C. chinensis were coarsely se-parated by macroporous adsorption resin, purified by column chromatography with D151 cation exchange resin, ODS and MCI, combined with semi-preparative high performance liquid chromatography. Two new alkaloid glycosides were obtained, and their structures were identified by mass spectrometry and NMR data as(S)-7-hydroxy-1-(p-hydroxybenzyl)-2,2-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-6-O-ß-D-glucopyranoside and(S)-N-methyltetrahydropalmatubine-9-O-ß-D-glucopyranoside, respectively. This study is of great significance for enriching the information about the chemical composition and the in-depth development of C. chinensis. Meanwhile, it can provide a reference for rapid identification and isolation of alkaloid glycosides from other Chinese herbal medicines.

Morphological and molecular characterization of Isospora elliotae n. sp. (Apicomplexa: Eimeriidae) from the Australian magpie Gymnorhina tibicen (Latham, 1801) (Passeriformes: Artamidae) in Western Australia.

A new coccidian species, Isospora elliotae n. sp., from the Australian magpie Gymnorhina tibicen (Latham, 1801) in Western Australia, is described and characterized morphologically and molecularly. Microscopic analysis of a faecal sample identified subspheroidal oocysts (n = 20), 20-22 × 18-20 (20.7 × 18.7); length/width (L/W) ratio 1.05-1.14 (1.10). Wall bi-layered, 1.0-1.3 (1.2) thick, outer layer smooth, c. 2/3 of total thickness. Micropyle and oocyst residuum absent, but usually two polar granules are present. Sporocysts (n = 28) ovoidal, 12-13 × 9-11 (12.6 × 9.7); L/W ratio 1.22-1.35 (1.30). Stieda body present, flattened to half-moon-shaped, c. 0.5 deep × 2.0 wide; sub-Stieda indistinct or barely discernible, c. 1.0 deep × 2.5 wide; para-Stieda body absent; sporocyst residuum present, composed of granules dispersed among the sporozoites. Sporozoites vermiform, with anterior and posterior refractile bodies and nucleus. Segments of three gene loci (18S rRNA, 28S rRNA and COI) were sequenced and I. elliotae n. sp. exhibited 99.8% genetic similarity to Isospora sp. MAH-2013a (KF648870) followed by 99.7% genetic similarity to Isospora neochmiae (Yang, Brice & Ryan, 2016) (KT224380) at the 18S rRNA gene locus. It shared 97.0% genetic similarity with an unnamed Isospora sp. (AY283852) at the 28S rRNA gene locus and it also shared the highest genetic similarity of 99.8% with the unnamed Isospora sp. from an American crow (OL999120) at the COI gene locus. Based on morphological and molecular data, this isolate is a new species named as I. elliotae n. sp.

Causal Effects of Gut Microbiota on Age-Related Macular Degeneration: A Mendelian Randomization Study.

Purpose: Recently, the association between gut microbiota and age-related macular degeneration (AMD) through the gut-retina axis has attracted great interest. However, the causal relationship between them has not been elucidated. Using publicly available genome-wide association study summary statistics, we conducted a two-sample Mendelian randomization (MR) analysis to examine the causal relationship between the gut microbiota and the occurrence of AMD. Methods: The study used a variety of quality control techniques to select instrumental single nucleotide polymorphisms (SNPs) with strong exposure associations. We used a set of SNPs as instrumental variable that were below the genome-wide statistical significance threshold (5 × 10-8). Additionally, a separate group of SNPs below the locus-wide significance level (1 × 10-5) were selected as instrumental variables to ensure a comprehensive conclusion. Inverse variance-weighted (IVW) analysis was the primary technique we used to examine causality in order to confirm the validity of our findings. The MR-Egger intercept test, Cochran's Q test, and leave-one-out sensitivity analysis were used to evaluate the horizontal pleiotropy, heterogeneities, and stability of the genetic variants. Results: IVW results showed that genus Anaerotruncus (P = 5.00 × 10-3), genus Candidatus Soleaferrea (P = 1.83 × 10-2), and genus unknown id.2071 (P = 3.12 × 10-2) were protective factors for AMD. The Eubacterium oxidoreducens group (P = 3.17 × 10-2), genus Faecalibacterium (P = 2.67 × 10-2), and genus Ruminococcaceae UCG-011 (P = 4.04 × 10-2) were risk factors of AMD. No gut microbiota (GM) taxa were found to be causally related to AMD at the phylum, class, order, and family levels (P > 0.05). The robustness of MR results were confirmed by heterogeneity and pleiotropy analysis. (P > 0.05). We also performed a bidirectional analysis, which showed that genus Anaerotruncus, genus Candidatus Soleaferrea, genus unknown id.2071 and the Eubacterium oxidoreducens group had an interaction with AMD, whereas genus Faecalibacterium showed only a unilateral unfavorable effect on AMD. Conclusions: We confirmed a causal relationship between AMD and GM taxa, including the Eubacterium oxidoreducens group, Faecalibacterium, Ruminococcaceae UCG-011, Anaerotruncus, and Candidatus Soleaferrea. These strains have the potential to serve as new biomarkers, offering valuable insights into the treatment and prevention of AMD.

Development and validation of a nomogram model for central venous access device-related thrombosis in hospitalized children.

This study aimed to develop and validate a nomogram model of central venous access device-related thrombosis (CRT) for hospitalized children. A total of 503 consecutive cases from a hospital in Changsha City, Hunan Province were stochastically classified into the training set and internal validation set at a ratio of 7:3, and 85 consecutive cases in two hospitals in Urumqi City, Xinjiang Uygur Autonomous Region were collected as an external validation set. Univariate analysis and multivariate analysis on CRT-related risk factors of hospitalized children were conducted, a logistic regression model was employed to establish the nomogram, and the discrimination, calibration, and decision curve analysis was performed to assess the proposed nomogram model. The nomogram model involved seven independent risk factors, including blind catheterization, abnormal liver function, central line-associated bloodstream infection, infection, number of catheter lines, leukemia, and bed rest > 72 h. The discrimination results showed that the area under the receiver operating characteristic curve of the training set, internal validation set, and external validation set was 0.74, 0.71, and 0.76 respectively, and the accuracy rates of the proposed nomogram model were 79%, 72%, and 71% in the training set, internal validation set, and external validation set. The calibration results also showed that the calibration curve had great fitness for each dataset. More importantly, the decision curve suggested that the proposed nomogram model had a prominent clinical significance. CONCLUSION: The nomogram model can be used as a risk assessment tool to reduce the missed diagnosis rate and the incidence of CRT in hospitalized children. WHAT IS KNOWN: • Central venous access device-related thrombosis is generally asymptomatic for hospitalized children, causing the missed diagnosis of central venous access device-related thrombosis easily. • No risk prediction nomogram model for central venous access device-related thrombosis in hospitalized children has been established. WHAT IS NEW: • A visual and personalized nomogram model was built by seven accessible variables (blind catheterization, abnormal liver function, central line-associated bloodstream infection, infection, number of catheter lines, leukemia, and bed rest > 72 h). • The model can effectively predict the risk of central venous access device-related thrombosis for hospitalized children.

Quality Marker Discovery and Quality Evaluation of Eucommia ulmoides Pollen Using UPLC-QTOF-MS Combined with a DPPH-HPLC Antioxidant Activity Screening Method.

Pollen, as an important component of Eucommia ulmoides (EUP), is rich in nutrients and is receiving increasing attention. At present, there are no reports on research related to the chemical composition and quality standards of EUP, and there are significant quality differences and counterfeit phenomena in the market. This study used a UPLC-QTOF-MS system to identify 49 chemical components in EUP for the first time. In the second step, 2,2-diphenyl-1-picrylhydrazyl (DPPH)-HPLC antioxidant activity screening technology was used to identify the main active components of EUP, quercetin-3-O-sophoroside (QSH), quercetin-3-O-sambubioside (QSB), and quercetin 3-O-neohesperidoside (QNH), and their purification, preparation, and structure identification were carried out. Third, molecular docking was used to predict the activity of these components. Fourth, the intracellular ROS generation model of RAW264.7 induced by H2O2 was used to verify and evaluate the activity of candidate active ingredients to determine their feasibility as Q-markers. Finally, a quality control method for EUP was constructed using the three selected components as Q-markers. The identification of chemical components and the discovery, prediction, and confirmation of characteristic Q-markers in EUP provide important references for better research on EUP and the effective evaluation and control of its quality. This approach provides a new model for the quality control of novel foods or dietary supplements.