Purification of triterpenoid saponins and 25R/25S-inokosterone from Achyranthes bidentata Bl. by high-speed countercurrent chromatography coupled silver nitrate coordination.

An effective method by high-speed countercurrent chromatography coordinated with silver nitrate for the preparative separation of sterones and triterpenoid saponins from Achyranthes bidentata Blume was developed. Methyl tert-butyl ether/n-butanol/acetonitrile/water (4:2:3:8, v/v/v/v) was selected for 20-hydroxyecdysone (compound 1), chikusetsusaponin IVa methyl ester (compound 4), 2'-glycan-11-keto-pigmented saponin V (compound 5), as well as a pair of isomers of 25S-inokosterone (compound 2) and 25R-inokosterone (compound 3), which were further purified by silver nitrate coordinated high-speed countercurrent chromatography. What is more, dichloromethane/methanol/isopropanol/water (6:6:1:4, v/v/v/v) was applied for calenduloside E (compound 6), 3ß-[(O-ß-d-glucuronopyranosyl)-oxy]-oleana-11,13-dien-28-oic acid (compound 7), zingibroside R1 (compound 8) and chikusetsusaponin IVa (compound 9). Adding Ag+ to the solvent system resulted in unique selectivity for 25R/25S isomers of inokosterone, which increased the complexing capability and stability of Ag+ coordinated 25S-inokosterone, as well as the α value between them. These results were further confirmed by the computational calculation of geometry optimization and frontier molecular orbitals assay. Comprehensive mass spectrometry and nuclear magnetic resonance analysis demonstrated the structures of the obtained compounds.

[Analysis of constituents in different parts of Forsythia suspensa by UPLC-Q-TOF-MS and evaluation of their anti-inflammatory activity].

This study aims to characterize and identify the chemical constituents in 11 parts of Forsythia suspensa by using ultra-performance liquid chromatography-quadrupole time of flight-mass spectrometry(UPLC-Q-TOF-MS) combined with a self-established chemical constituent database, including leaves, flowers, fruits, green F. suspensa, old F. suspensa, and seeds. The quality attributes and differences of different parts of F. suspensa were evaluated by principal component analysis, partial least square discriminant analysis, and other stoichiometric methods. A total of 79 compounds were identified, including 13 phenylethanol glycosides, 10 lignans, 12 flavonoids, 10 organic acids, 14 terpenoids, and 20 other types of compounds. Among them, 34 compounds were the main variables of difference between the different parts of F. suspensa, and the content of each component was relatively higher in the leaves and green F. suspensa. The LPS-induced inflammation model of RAW264.7 cells was applied to study the anti-inflammatory activity of the extracts of the different parts of F. suspensa and the main constituents. The results show that the extracts of green F. suspensa, flower, twig, and stem exhibited anti-inflammatory activity, and the constituents such as forsythoside A, phyllyrin, phillygenin, and(+)-pinoresinol-ß-D-glucopyranoside could significantly inhibit anti-inflammatory activity released by NO. The chemical constituent in different parts of F. suspensa is analyzed comprehensively, and the anti-inflammatory activity is evaluated in this study, which provides a reference for the development and comprehensive utilization of F. suspensa resources.

[A new sesquiterpenoid from Lindera aggregata].

The chemical composition of the aqueous part of the extract from Lindera aggregata was studied, which was separated and purified by the macroporous resin column chromatography, MCI medium pressure column chromatography, semi-preparative high-performance liquid phase and other methods. The structures of the compounds were identified according to physical and chemical properties and spectroscopic data. Thirteen compounds were isolated and identified from the aqueous extracts, which were identified as(1S,3R,5R,6R,8S,10S)-epi-lindenanolide H(1), tachioside(2), lindenanolide H(3), leonuriside A(4), 3,4-dihydroxyphenyl ethyl ß-D-glucopyranoside(5), 3,4,5-trimethoxyphenol-1-O-6-α-L-rhamnose-(1→6)-O-ß-D-glucoside(6), 5-hydroxymethylfurfural(7),(+)-lyoniresin-4-yl-ß-D-glucopyranoside(8), lyoniside(9), norboldine(10), norisopordine(11), boldine(12), reticuline(13). Among them, compound 1 was a new one, and compounds 2, 5, 6, 8, 9 were obtained from L. aggregata for the first time. The inflammatory model was induced by lipopolysaccharide(LPS) in the RAW264.7 cells. The results showed that compounds 1, 8, 10 and 12 had significant anti-inflammatory activity.

Integrated spatial metabolomics and transcriptomics decipher the hepatoprotection mechanisms of wedelolactone and demethylwedelolactone on non-alcoholic fatty liver disease.

Eclipta prostrata L. has been used in traditional medicine and known for its liver-protective properties for centuries. Wedelolactone (WEL) and demethylwedelolactone (DWEL) are the major coumarins found in E. prostrata L. However, the comprehensive characterization of these two compounds on non-alcoholic fatty liver disease (NAFLD) still remains to be explored. Utilizing a well-established zebrafish model of thioacetamide (TAA)-induced liver injury, the present study sought to investigate the impacts and mechanisms of WEL and DWEL on NAFLD through integrative spatial metabolomics with liver-specific transcriptomics analysis. Our results showed that WEL and DWEL significantly improved liver function and reduced the accumulation of fat in the liver. The biodistributions and metabolism of these two compounds in whole-body zebrafish were successfully mapped, and the discriminatory endogenous metabolites reversely regulated by WEL and DWEL treatments were also characterized. Based on spatial metabolomics and transcriptomics, we identified that steroid biosynthesis and fatty acid metabolism are mainly involved in the hepatoprotective effects of WEL instead of DWEL. Our study unveils the distinct mechanism of WEL and DWEL in ameliorating NAFLD, and presents a "multi-omics" platform of spatial metabolomics and liver-specific transcriptomics to develop highly effective compounds for further improved therapy.

Chaotropic Effect-Induced Sol-Gel Transition and Radical Stabilization for Bacterially Sensitive Near-Infrared Photothermal Therapy.

Deep-seated bacterial infections (DBIs) are stubborn and deeply penetrate tissues. Eliminating deep-seated bacteria and promoting tissue regeneration remain great challenges. Here, a novel radical-containing hydrogel (SFT-B Gel) cross-linked by a chaotropic effect was designed for the sensing of DBIs and near-infrared photothermal therapy (NIR-II PTT). A silk fibroin solution stained with 4,4',4″-(1,3,5-triazine-2,4,6-triyl)tris(1-methylpyridin-1-ium) (TPT3+) was employed as the backbone, which could be cross-linked by a closo-dodecaborate cluster (B12H122-) through a chaotropic effect to form the SFT-B Gel. More interestingly, the SFT-B Gel exhibited the ability to sense DBIs, which could generate a TPT2+• radical with obvious color changes in the presence of bacteria. The radical-containing SFT-B Gel (SFT-B★ Gel) possessed strong NIR-II absorption and a remarkable photothermal effect, thus demonstrating excellent NIR-II PTT antibacterial activity for the treatment of DBIs. This work provides a new approach for the construction of intelligent hydrogels with unique properties using a chaotropic effect.

[Effects of Application of Different Organic Materials on Phosphorus Accumulation and Transformation in Vegetable Fields].

Presently, the improvement of soil organic matter is the basis to ensure food security, but the accumulation and transformation characteristics of soil phosphorus (P) as affected by organic matter remain unclear. The accumulation, transformation, and migration characteristics of soil P in different soil layers of vegetable fields were researched under the application of organic materials. Six treatments were set up in the experiment:control (no fertilization), traditional fertilizer application by farmers, biochar, chicken manure, food waste, and straw application. Available phosphorus (Olsen-P), water-soluble phosphorus (CaCl2-P) content, soil phosphorus forms, soil organic matter (SOM), and pH were determined during the pepper harvest period. In the 0-5 cm and 5-10 cm soil layers, the available phosphorus content of traditional fertilization of farmers was higher, and the available phosphorus content of the four organic materials was in the order of straw > biochar > chicken manure > food waste. Compared to that with food waste, the straw and biochar treatments increased soil available phosphorus by 59.6%-67.3% and 29.1%-36.9%, respectively. The straw treatment could easily enhance the soil labile P pool, and soil labile P in the 0-5 cm soil layer increased by 47.3% and 35.1% compared with that under the chicken manure and food waste treatments, respectively. With the increase in soil depth, the proportion of available phosphorus in the chicken manure treatment decreased the least, and available phosphorus of the 20-30 cm soil layer accounted for 55.9% of the topsoil layer but only accounted for 16.0%-34.0% under treatment with the other three materials. Compared with that under the traditional fertilization of farmers, the pH significantly increased by 0.18-0.36 units after the application of organic fertilizer, and the pH of the chicken manure and food waste treatments was significantly higher than that of biochar and straw (P < 0.05). SOM content under the biochar treatment significantly increased by 7.7%-17.6% compared to that under the other three organic materials. Among the four organic materials, the straw treatment boosted the labile P pool the most, which was conducive to the rapid increase in plant-available P. Phosphorus was most likely to migrate downward under the chicken manure treatment. In the field management based on soil fertility enhancement, the application of biochar could not only improve soil pH and SOM but also avoid excessive accumulation of phosphorus in the surface layer, which decreases environmental risks.

[Resources and utilization of medicinal plants in countries and regions involved in "the Belt and Road" Initiative].

The protection, development, and utilization of medicinal plant resources are important cornerstones of maintaining human health. However, due to factors such as the reduction of high-quality land resources, deterioration of ecological environments, and excessive and disorderly resource development, medicinal plant resources are becoming scarce, and some of them are insufficiently supplied. With the proposal of "the Belt and Road" Initiative, the cooperation between China and "the Belt and Road" partners(the countries and regions involved in "the Belt and Road" Initiative)is increasingly close, which provides a new opportunity for carrying out trade of medicinal plant resources and alleviating the problem of imbalance and relative inadequacy of medicinal plant resources in countries. This study first determined the distribution and species information of plant resources in countries and regions involved in "the Belt and Road" Initiative by investigating the database of plant distribution and that of medicinal plant resources. Then, according to the published data from the International Union for Conservation of Nature(IUCN) and the Convention on International Trade in Endangered Species of Wild Fauna and Flora(CITES), this study identified the rare and endangered medicinal plants and the medicinal plants under trade control in countries and regions involved in "the Belt and Road" Initiative and finally sorted out the list of potential medicinal plant resources in countries and regions involved in "the Belt and Road" Initiative that can be used by China. This data resource can not only be used for the overall protection of important endangered species but also scientifically guide the development and utilization of medicinal resources, providing guidance and a theoretical basis for the sustainable development of medicinal plant resources in countries and regions involved in "the Belt and Road" Initiative.

Hidden diversity and potential ecological function of phosphorus acquisition genes in widespread terrestrial bacteriophages.

Phosphorus (P) limitation of ecosystem processes is widespread in terrestrial habitats. While a few auxiliary metabolic genes (AMGs) in bacteriophages from aquatic habitats are reported to have the potential to enhance P-acquisition ability of their hosts, little is known about the diversity and potential ecological function of P-acquisition genes encoded by terrestrial bacteriophages. Here, we analyze 333 soil metagenomes from five terrestrial habitat types across China and identify 75 viral operational taxonomic units (vOTUs) that encode 105 P-acquisition AMGs. These AMGs span 17 distinct functional genes involved in four primary processes of microbial P-acquisition. Among them, over 60% (11/17) have not been reported previously. We experimentally verify in-vitro enzymatic activities of two pyrophosphatases and one alkaline phosphatase encoded by P-acquisition vOTUs. Thirty-six percent of the 75 P-acquisition vOTUs are detectable in a published global topsoil metagenome dataset. Further analyses reveal that, under certain circumstances, the identified P-acquisition AMGs have a greater influence on soil P availability and are more dominant in soil metatranscriptomes than their corresponding bacterial genes. Overall, our results reinforce the necessity of incorporating viral contributions into biogeochemical P cycling.

A Rare Case of Benign Recurrent Intrahepatic Cholestasis Initially Diagnosed in Middle-age.

Background: Repeated episodes of jaundice and pruritus are common in a group of autosomal recessive liver diseases known as benign recurrent intrahepatic cholestasis. Benign recurrent intrahepatic cholestasis (BRIC) is divided into two types, type 1 and type 2, and is caused by mutations in the ATP8B1 and ABCB11 genes. Here, we report a rare case of BRIC type 2 mutation. Case presentation: A 45-year-old Chinese man had three frequent episodes of jaundice marked by extensive excoriation and severe pruritis, although he had no prior history of jaundice. Laboratory investigations showed no evidence of liver damage caused by viral, autoimmune, or acquired metabolic etiologies. The CT scan revealed an enlarged gallbladder with numerous punctate high-density shadows, while no wall thickening was observed. Endoscopic ultrasonography showed no evidence of dilation of the intrahepatic and extrahepatic bile duct, as well as the absence of gallstone. Diagnostic evaluation: Immunohistochemical examinations of liver biopsy samples showed cytokeratin-7 positive hepatocytes, suggesting chronic intrahepatic cholestasis. The reticulin fiberstaining demonstrated that the portions of the hepatic plate in the center of the lobule were asymmetrically organized,and somewhat enlarged, with collapsed areas indicating intralobular inflammation. Moreover, there were areas of collapse that indicated the presence of intralobular inflammation. Whole exome sequencing revealed mutations in the ABCB11 gene; c.3084A>G, p.A1028A homozygous mutation (chr2-169789016), and c.2594C>T, p.A865V heterozygous mutation (chr2-169801131). Based on these findings, the final diagnosis of the patient was metabolism-related jaundice. Treatment: Apart from receiving tapering dosage of prednisone to lower bilirubin levels, the patient received no extra care. Conclusion: The comprehensive diagnosis of a middle-aged male patient with BRIC-2, which involved extensive radiological, hematological, and genetic investigations, informed a tailored tapering prednisone regimen, highlighting the importance of personalized medicine in managing atypical presentations of this rare cholestatic disorder.

Multi-modal molecular determinants of clinically relevant osteoporosis subtypes.

Due to a rapidly aging global population, osteoporosis and the associated risk of bone fractures have become a wide-spread public health problem. However, osteoporosis is very heterogeneous, and the existing standard diagnostic measure is not sufficient to accurately identify all patients at risk of osteoporotic fractures and to guide therapy. Here, we constructed the first prospective multi-omics atlas of the largest osteoporosis cohort to date (longitudinal data from 366 participants at three time points), and also implemented an explainable data-intensive analysis framework (DLSF: Deep Latent Space Fusion) for an omnigenic model based on a multi-modal approach that can capture the multi-modal molecular signatures (M3S) as explicit functional representations of hidden genotypes. Accordingly, through DLSF, we identified two subtypes of the osteoporosis population in Chinese individuals with corresponding molecular phenotypes, i.e., clinical intervention relevant subtypes (CISs), in which bone mineral density benefits response to calcium supplements in 2-year follow-up samples. Many snpGenes associated with these molecular phenotypes reveal diverse candidate biological mechanisms underlying osteoporosis, with xQTL preferences of osteoporosis and its subtypes indicating an omnigenic effect on different biological domains. Finally, these two subtypes were found to have different relevance to prior fracture and different fracture risk according to 4-year follow-up data. Thus, in clinical application, M3S could help us further develop improved diagnostic and treatment strategies for osteoporosis and identify a new composite index for fracture prediction, which were remarkably validated in an independent cohort (166 participants).

[Evolution and implementation pathways from desertification prevention and control to sandy land management and use in China]. / 中国从防沙治沙到管沙用沙的演变过程与实现路径.

The construction of ecological civilization emphasizes holistic protection of "mountain-water-forest-farmland-lake-grassland-sand", which has become an important concept of desertification prevention projects in arid and semi-arid areas of China. In the past, sandy land management and use have been neglected in desertification prevention and control, in that the links have not been effectively connected and the long-term and efficient desertification prevention has not been realized. Therefore, combining Qian Xuesen's understanding of "deserticulture", we comprehensively discussed the "long-term achievements" of China's desertification control miracle from the perspective of the historical evolution of the interaction of technology and practice, and the strategic development of policy guidance. Further, we defined the concepts of desertification prevention, desertification control, and sandy land management and use. We analyzed the coupling and coordination relationship between the four links and the scientific principle based on the development of ecological industry chain. Finally, we put forward the policy and market realization pathways, with efficient sandy land management as the core, desertification prevention as the basis, desertification control as the channel, and long-term sandy land use as the foundation. We expected to provide theoretical and practical guidance for creating a new miracle of China's desertification prevention and control.

Efficacy comparison between acupuncture and other modalities in the treatment of rotator cuff diseases: meta-analysis of randomized controlled trials.

OBJECTIVE: This study aimed to analyze the efficacy of acupuncture alone or combined with physical therapy compared to other treatment interventions for relieving pain and improving function in rotator cuff diseases. METHODS: Our study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After PROSPERO (CRD42023396740) registration, all randomized controlled trials (RCTs) published from the inception of the databases to October 10, 2023, evaluating the efficacy of acupuncture either alone or in combination with physical therapy for treating rotator cuff diseases, were extracted from seven databases, including PubMed, Embase, the Web of Science, the Cochrane Library, the China National Knowledge Infrastructure (CNKI), the VIP Database for Chinese Technical Periodicals (VIP), and the Wanfang Date. Two independent researchers assessed the quality of the included studies and extracted relevant data. Furthermore, a meta-analysis was conducted using Stata 14 software. RESULTS: We included 13 RCTs - 12 published in English and 1 in Chinese - that enrolled 1,371 patients. The meta-analysis results demonstrated that acupuncture alone or in combination with physical therapy was superior to other interventions for short-term shoulder joint function improvement (standardized mean difference [SMD] = -0.82, 95% confidence interval [95% CI]: -1.28 to -0.35, P = 0.001), medium-term shoulder joint function improvement (SMD = -1.00, 95% CI: -1.62 to -0.38, P = 0.002), short-term pain relief (weighted mean difference [WMD] = -1.37, 95% CI: -2.39 to -0.38, P = 0.006), medium-term pain relief (WMD = -1.66, 95% CI: -2.70 to -0.63, P = 0.002), and post-treatment shoulder joint abduction improvements (SMD = 0.68, 95% CI: 0.20 to 1.16, P = 0.005), external rotation (SMD = 0.62, 95% CI: 0.13 to 1.11, P = 0.012), and forward flexion (SMD = 0.71, 95% CI: 0.44 to 0.97, P < 0.001), with significant differences (P < 0.05). CONCLUSION: Based on the current clinical data, meta-analysis showed that acupuncture alone or combined with physical therapy is efficacious for short- and medium-term (< 3 months) pain relief and functional improvements. However, compared to other interventions, the efficacy of the long-term (3 to 12 months) period did not significantly differ. After treatment, these modalities displayed advantages such as improved shoulder joint abduction, external rotation, and forward flexion movements. However, no significant difference was noted in internal rotation movement. Thus, future studies might further investigate whether different acupuncture methods affect the efficacy of treating rotator cuff diseases and improving long-term outcome.

Integrated network pharmacology and pharmacological investigations to explore the potential mechanism of Ding-Chuan-Tang against chronic obstructive pulmonary disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Ding-Chuan-Tang (Abbreviated as DCT) is frequently prescribed for treatment of respiratory diseases, including chronic obstructive pulmonary disease (COPD), which is characterized by coughing, wheezing, and chest tightness in traditional Chinese medicine (TCM). However, the potential mechanism of DCT has not been investigated. AIM OF STUDY: The aim of the study is to explore the efficiency of DCT in the treatment of COPD in vivo and in vitro, and to illustrate the possible mechanism against COPD. METHODS: COPD model was induced by exposure of mice to cigarette smoke (CS) for 16 weeks. Enzyme-linked immunosorbent assay (ELISA), immunofluorescence assay, Western blot, etc., were used to explore the efficiency and mechanisms of DCT. Network pharmacology analysis, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, etc., was performed to explore the potential targets in the treatment of DCT on COPD. RESULTS: DCT significantly alleviated pulmonary pathological changes in mouse COPD model, and inhibited inflammatory response induced by CS and LPS in vivo and in vitro. Network pharmacology analysis suggested that DCT alleviated COPD via inhibiting inflammation by regulating PI3K-AKT pathway. In cell-based models, DCT suppressed the phosphorylation of PI3K and AKT, which further regulated its downstream targets Nrf2 and NF-κB, and inhibited inflammatory response. CONCLUSIONS: DCT effectively attenuated COPD in the mouse model induced by CS. The therapeutic mechanism of DCT against COPD was closely associated with the regulation of PI3K-AKT pathway and its downstream transcription factors, Nrf2 and NF-κB.

Effect of resveratrol on herpesvirus encephalitis: Evidences for its mechanisms of action.

BACKGROUND: Herpes simplex virus type 1 (HSV-1)-induced herpes simplex encephalitis (HSE) has a high mortality rate in clinically immunocompromised patients, while recovered patients often experience neurological sequelae due to neuroinflammation. Nucleoside drugs and nucleoside analogues such as acyclovir and ganciclovir are mainly used in clinical treatment, and the emergence of resistant viral strains makes the development of new anti-herpesvirus encephalitis drugs urgent. Resveratrol is a multifunctional, plant-derived bioactive compound and its antiviral potential is attracting much attention. PURPOSE: This study aimed to investigate the anti-HSV-1 mechanism of resveratrol in microglial cells and in the HSE mouse model. METHODS: The antiviral effect of resveratrol on HSV-1 infection was investigated by plaque assay, virus titer, immunofluorescence, Western blot and time-of-addition assay. The influence of resveratrol on stimulator of interferon gene (STING)/Nuclear Factor kappa B (NF-κB) signaling pathway-mediated neuroinflammation was examined by Western blot, RT-qPCR and ELISA. The interaction between resveratrol and STING/heat shock protein 90 beta (HSP90ß) was evaluated by molecular modeling, co-immunoprecipitation, and drug affinity responsive target stability assay. The therapeutic effect of resveratrol on HSE was evaluated in the HSE mouse model by analyzing weight loss, neurodegenerative symptoms and histopathological scores. RESULTS: Resveratrol inhibited the early process of HSV-1 infection, and interfered with the STING/NF-κB signaling pathway to attenuate HSV-1-induced neuroinflammation and microglial M1 polarization, independent of its classical target Sirtuin1. Mechanistically, resveratrol completely bound to Glu515 and Lys491 of HSP90ß, thus disrupting the HSP90ß-STING interaction and promoting STING degradation. Resveratrol also significantly alleviated viral encephalitis and neuroinflammation caused by HSV-1 in the HSE mouse model. CONCLUSION: Resveratrol acted as a non-classical HSP90ß inhibitor, binding to the STING-HSP90ß interaction site to promote STING degradation and attenuate HSV-1-induced encephalitis and neuroinflammation. These findings suggest the alternative strategy of targeting HSP90ß and resveratrol-mediated inhibition of HSP90ß as a potential antiviral approach.

Analyzing chemical composition of Sargentodoxae caulis water extract and their hypouricemia effect in hyperuricemic mice.

Hyperuricemia (HUA) is a metabolic disease characterized by the increase of serum uric acid (UA) level. Sargentodoxae Caulis (SC) is a commonly used herbal medicine for the treatment of gouty arthritis, traumatic swelling, and rheumatic arthritis in clinic. In this study, a total of fifteen compounds were identified in SC water extract using UHPLC-Q-TOF-MS/MS, including three phenolic acids, seven phenolic glycosides, four organic acids, and one lignan. Then, to study the hypouricemia effect of SC, a HUA mouse model was induced using a combination of PO, HX, and 20% yeast feed. After 14 days of treatment with the SC water extract, the levels of serum UA, creatinine (CRE), blood urea nitrogen (BUN) were reduced significantly, and the organ indexes were restored, the xanthine oxidase (XOD) activity were inhibited as well. Meanwhile, SC water extract could ameliorate the pathological status of kidneys and intestine of HUA mice. Additionally, quantitative real-time PCR (qRT-PCR) and western blotting results showed that SC water extract could increase the expression of ATP binding cassette subfamily G member 2 (ABCG2), organic cation transporter 1 (OCT1), organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3), whereas decrease the expression of glucose transporter 9 (GLUT9). This study provided a data support for the clinical application of SC in the treatment of HUA.

Matrine reduced intestinal stem cell damage in eimeria necatrix-infected chicks via blocking hyperactivation of Wnt signaling.

BACKGROUND: Coccidiosis is a rapidly spreading and acute parasitic disease that seriously threatening the intestinal health of poultry. Matrine from leguminous plants has anthelmintic and anti-inflammatory properties. PURPOSE: This assay was conducted to explore the protective effects of Matrine and the AntiC (a Matrine compound) on Eimeria necatrix (EN)-infected chick small intestines and to provide a nutritional intervention strategy for EN injury. STUDY DESIGN: The in vivo (chick) experiment: A total of 392 one-day-old yellow-feathered broilers were randomly assigned to six groups in a 21-day study: control group, 350 mg/kg Matrine group, 500 mg/kg AntiC group, EN group, and EN + 350 mg/kg Matrine group, EN + 500 mg/kg AntiC group. The in vitro (chick intestinal organoids, IOs): The IOs were treated with PBS, Matrine, AntiC, 3 µM CHIR99021, EN (15,000 EN sporozoites), EN + Matrine, EN + AntiC, EN + Matrine + CHIR99021, EN + AntiC + CHIR99021. METHODS: The structural integrity of chicks jejunal crypt-villus axis was evaluated by hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM). And the activity of intestinal stem cells (ISCs) located in crypts was assessed by in vitro expansion advantages of a primary in IOs model. Then, the changes of Wnt/ß-catenin signaling in jejunal tissues and IOs were detected by Real-Time qPCR,Western blotting and immunohistochemistry. RESULTS: The results showed that dietary supplementation with Matrine or AntiC rescued the jejunal injury caused by EN, as indicated by increased villus height, reduced crypt hyperplasia, and enhanced expression of tight junction proteins. Moreover, there was less budding efficiency of the IOs expanded from jejunal crypts of chicks in the EN group than that in the Matrine and AntiC group, respectively. Further investigation showed that AntiC and Matrine inhibited EN-stimulated Wnt/ß-catenin signaling. The fact that Wnt/ß-catenin activation via CHIR99021 led to the failure of Matrine and AntiC to rescue damaged ISCs confirmed the dominance of this signaling. CONCLUSION: Our results suggest that Matrine and AntiC inhibit ISC proliferation and promote ISC differentiation into absorptive cells by preventing the hyperactivation of Wnt/ß-catenin signaling, thereby standardizing the function of ISC proliferation and differentiation, which provides new insights into mitigating EN injury by Matrine and AntiC.

Screening and characterization of potential anti-gout components from Polygonum cuspidatum by integration off-line two-dimensional liquid chromatography-mass spectrometry with affinity ultrafiltration and on-line HPLC-ABTS.

Polygonum cuspidatum (P. cuspidatum) is a traditional herbal medicine with a long history and proven efficacy in treating gout. However, due to the complexity of composition and extensive content distribution, the substance basis of its anti-gout effectiveness is still unclear. A strategy was proposed via integrating off-line two-dimensional liquid chromatography (2D-LC) and targeted rapid screening technology based on ultrafiltration-liquid chromatography-mass spectrometry (UF-LC/MS) and on-line high-performance liquid chromatography-2, 2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (HPLC-ABTS) to accomplish high coverage and high throughput screening of anti-gout components from P. cuspidatum. As a result, twenty components were screened from P. cuspidatum extract with both xanthine oxidase (XOD) inhibitory activity and free radical scavenging activity, then were preliminarily identified by high-resolution electrospray ionization-quadrupole-time-of-flight mass spectrometer (ESI-Q-TOF/MS). The screened results were verified by the in vitro assays. Meanwhile, molecular docking further elucidated that the screened bioactive ingredients had favourable binding capabilities with XOD. The performance of this study can achieve high efficiency and high coverage screening of the anti-gout components from P. cuspidatum, which provides methodology and strategy support for the rapid screening of bioactive ingredients from complex medicinal plants.

Tonghua Liyan granules in the treatment of Laryngopharyngeal reflux disease with stagnation of phlegm and qi syndrome: a randomized, double-blind, placebo-controlled study.

Background: Laryngopharyngeal reflux disease (LPRD) is an extraesophageal syndromic manifestation of gastroesophageal reflux disease (GERD). Despite the increasing incidence of and concern about LPRD, treatment with proton pump inhibitors (PPIs) is unsatisfactory. Here, LPRD was treated with Tonghua Liyan (THLY) granules in combination with PPIs to evaluate treatment efficacy and possible adverse reactions. Methods: Seventy-six LPRD patients with stagnation of phlegm and qi syndrome (SPQS) were randomly divided into an experimental group and a control group. The experimental group received THLY granules combined with rabeprazole capsules. The control group received THLY granule placebo combined with rabeprazole capsules. A parallel, randomized, double-blind, placebo-controlled clinical trial was conducted with these two groups. The treatment cycle was 8 weeks. The reflux symptom index (RSI), clinical symptom score, salivary pepsin content, reflux finding score (RFS) and gastroesophageal reflux disease questionnaire (GerdQ) were used to evaluate clinical efficacy. The final efficacy rate was evaluated according to the RSI and clinical symptom score. Results: Compared with those at baseline, all the indicators in the experimental group and control group significantly improved (p < 0.01). In terms of the RSI, clinical symptom score, and RFS, the experimental group had a higher degree of improvement (p < 0.05), and the overall efficacy rate was higher (p < 0.05). In terms of the salivary pepsin concentration and GerdQ, there was no significant difference between the test group and the control group (p > 0.05). Both groups of safety indicators showed no abnormalities and did not cause any allergic reactions in the body. Conclusion: Compared with PPIs alone, THLY granules combined with PPIs are more effective in the treatment of LPRD patients with SPQS in terms of symptoms and signs. This combination treatment, because of its higher clinical efficacy and lack of obvious adverse reactions, is worthy of clinical promotion and further in-depth study. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2100046614.

Impact of Geriatric Experience Training on Nurses in Preventing Falls in Elderly Patients.

Objective: This study aimed to explore the effects of geriatric experience training on nurses from multiple primary healthcare units in the context of population aging. The study also evaluated the impact of this training on improving nurses' cognitive abilities in preventing falls/bedside accidents in elderly patients and implementing safe nursing practices to reduce the incidence of falls/bedside accidents. Methods: A total of 302 nurses involved in geriatric care from 18 primary healthcare units in the region were randomly categorized into 2 groups on a 1:1 basis. The control group received regular training on falls/bedside accident prevention for patients, whereas the observation group received additional geriatric experience training along with the regular training. Further, 420 elderly patients who experienced moderate-to-severe falls/bedside accidents between February and July 2022, with a Morse Fall Scale (MFS) score of ≥25 were randomly assigned to either the observation or control group on a 1:1 basis. This study compared the 2 groups in terms of nurses' awareness of falls/bedside accident risks, incidence of falls/bedside accidents in patients and patient satisfaction with fall/bedside accident prevention care. Results: No statistically significant differences were observed (P > .05) between the 2 groups of nurses, except in their awareness of the aging population and the increased risk for falls/bedside accidents in elderly patients. However, the observation group nurses scored higher in other aspects of falls/bedside accident risk awareness after undergoing geriatric experience training (P < .05). The incidence of falls/bedside accidents was significantly lower in the observation group than in the control group (P < .05). Patient satisfaction with falls/bedside accident prevention care was significantly higher in the observation group compared with the control group (P < .05). Conclusion: Geriatric experience training for nurses in multiple primary healthcare units in the region could effectively improve the capabilities of primary hospitals in preventing falls/bedside accidents.

Design of a Novel Lysine Isopeptide 1018KI11 with Potent Antimicrobial Activity as a Safe and Stable Food Preservative Candidate.

Antimicrobial peptides are potent food additive candidates, but most of them are sensitive to proteases, which limits their application. Therefore, we substituted arginine for lysine and introduced a lysine isopeptide bond to peptide IDR-1018 in order to improve its enzymatic stability. Subsequently, the protease stability and antimicrobial/antibiofilm activity of the novel peptides (1018K2-1018KI11) were investigated. The data revealed that the antienzymatic potential of 1018KI11 to bromelain and papain increased by 2-8 folds and 16 folds, respectively. The minimum inhibitory concentration (MIC) of 1018KI11 against methicillin-resistant Staphylococcus aureus (MRSA) ATCC43300 and Escherichia coli (E. coli) ATCC25922 was reduced 2-fold compared to 1018K11. Mechanism exploration suggested that 1018KI11 was more effective than 1018K11 in disrupting the cell barrier and damaging genomic DNA. Additionally, 1018KI11 at certain concentration conditions (2-64 µg/mL) reduced biofilm development of MRSA ATCC43300 by 4.9-85.9%. These data indicated that novel peptide 1018KI11 is a potential food preservative candidate.