Seven novel acylphloroglucinol-sesquiterpenoid adducts, designated as dryatraols J-P (1-7), were isolated from the rhizomes of Dryopteris atrata (Wall. ex Kunze) Ching. The structures, including absolute configurations, were elucidated using comprehensive spectroscopic data, calculated ¹³C Nuclear Magnetic Resonance-Diastereotopic Probability Assignment Plus (¹³C NMR-DP4+) probability analysis, and ECD calculations. These structures represent a rare subclass of carbon skeleton of acylphloroglucinol-sesquiterpenoid adducts with a furan ring connecting the acylphloroglucinol and sesquiterpenoid moieties. Notably, compounds 1-6 are the first reported examples of acylphloroglucinol-sesquiterpenoid adducts with dimeric acylphloroglucinol incorporated into the aristolane- or rulepidanol-type sesquiterpene, while compound 7 features a hydroxylated monomeric acylphloroglucinol motif. A preliminary evaluation of their antiviral activities revealed that compounds 1-6 exhibited more potent activities against respiratory syncytial virus (RSV) with IC₅₀ values ranging from 0.75 to 3.12 μmol·L^-1 compared to the positive control (ribavirin).
Antiviral Agents/isolation & purification* ; Phloroglucinol/isolation & purification* ; Sesquiterpenes/isolation & purification* ; Molecular Structure ; Dryopteris/chemistry* ; Respiratory Syncytial Viruses/drug effects* ; Humans ; Rhizome/chemistry* ; Drugs, Chinese Herbal/pharmacology*

Peganum harmala L. (P. harmala) is a significant economic and medicinal plant. The seeds of P. harmala have been extensively utilized in traditional Chinese medicine, Uighur medicine, and Mongolian medicine, as documented in the Drug Standard of the Ministry of Health of China. Twelve novel tryptamine-derived alkaloids (1-12) and eight known compounds (13-20) were isolated from P. harmala seeds. Compounds 1 and 2 represent the first reported instances of tryptamine-derived heteromers, comprising tryptamine and aniline fragments with previously undocumented C-3-N-1' linkage and C-3-C-4' connection, respectively. Compounds 3-5 were identified as indole-quinazoline heteromers, exhibiting a novel C-3 and NH-1' linkage between indole and quinazoline-derived fragments. Compound 6 demonstrates the dimerization pattern of C-C linked tryptamine-quinazoline dimer. Compound 8 represents a tryptamine-derived heterodimer with a distinctive carbon skeleton, featuring an unusual spiro-tricyclic ring (7) and conventional bicyclic tryptamine. Compounds 9-11 constitute novel 6/5/5/5 spiro-tetracyclic tryptamine-derived alkaloids presenting a unique ring system of tryptamine-spiro-pyrrolizine. Compounds 1-3 and 6-11 were identified as racemates. Compounds 2, 7, 9, 10, and 12 were confirmed via X-ray crystallographic analysis. All isolated compounds (1-20) exhibited varying degrees of antiviral efficacy against respiratory syncytial virus (RSV). Notably, the anti-RSV activity of compound 12 (IC₅₀ 5.01 ± 0.14 μmol·L^-1) surpassed that of the positive control (ribavirin, IC₅₀ 6.23 ± 0.95 μmol·L^-1), as validated through plaque reduction and immunofluorescence assays. The identification of anti-RSV compounds from P. harmala seeds may enhance the development and application of this plant in antiviral therapeutic products.
Antiviral Agents/isolation & purification* ; Tryptamines/isolation & purification* ; Peganum/chemistry* ; Seeds/chemistry* ; Alkaloids/isolation & purification* ; Molecular Structure ; Humans ; Respiratory Syncytial Viruses/drug effects* ; Plant Extracts/pharmacology* ; Drugs, Chinese Herbal/pharmacology*

Objective To explore the potential therapeutic targets and mechanisms of Shujinxi External Granules in the treatment of osteoarthritis(OA).Methods The chemical constituents and targets of Shujinxi External Granules were collected from TCMSP,TCMIP,TCMID and HERB databases,and the target genes related to OA were obtained from GEO database.Screening the overlapping targets,Cytoscape software was used to construct the"Shujinxi External Granules-compounds-OA-targets"and protein-protein interaction(PPI)networks.Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on the overlapping targets through DAVID database,and the compounds and proteins with the highest degree values were selected for molecular docking by using AutoDock Vina.Results There were 85 components and 915 targets were found in Shujinxi External Granules.The 4 383 targets of OA were obtained,and 248 overlapping targets were screened out between Shujinxi External Granules and OA.The key target proteins were epidermal growth factor receptor(EGFR),cyclin-dependent kinase 1(CDK1),matrix metalloproteinase 9(MMP9),and the key compounds were N-trans-feruloyltyramine,palmatine,balanophonin,aurantiamide acetate,Saroaspidin A,luteolin,schizandrin,rhynchophylline,rhynchophylline A,kaempferol,1-piperoylpiperidine.A total of 489 biological processes,162 cellular components and 87 molecular functions were obtained by using GO functional enrichment analysis,and 100 signaling pathways related to the therapeutic of Shujinxi External Granules were obtained by using KEGG pathway enrichment analysis.The molecular docking results showed that N-trans-feruloyltyramine,1-piperonoylpiperidine and rhynchophylline A had good binding ability to the key targets EGFR,CDK1 and MMP9,respectively.Conclusion The Shujinxi External Granules may bind to the key targets EGFR,CDK1,and MMP9 in the pathways in cancer,hypoxia-inducible factor 1(HIF-1)and calcium signaling pathway through the key active components,such as N-trans-feruloyltyramine,rhynchophylline A,and 1-piperoylpiperidine,to exert the therapeutic effects on OA.

Objective To explore the effect of 12-week simplified Tai Chi training on rehabilitation and neuromuscular control in individuals with chronic ankle instability(CAI).Methods Thirty-four partic-ipants with CAI were randomly divided into an experimental group and a control group,each of 17.The control group received 12-week health education,while the experimental group underwent simpli-fied Tai Chi training for the same length.Before and after the intervention,both groups were evaluat-ed their self-reported instability feeling,ankle muscle strength,proprioception and dynamic postural stability.Results After intervention,a significant increase was observed in the average Cumberland An-kle Instability Tool(CAIT),the maximum extension distance in the posteromedial and posterolateral di-rections of the modified Star Excursion Balance Test(mSEBT)in,as well as the ankle peak torque in plantarflexion,inversion and eversion(P<0.05)in the experimental.Moreover,the ankle passive motion proprioceptive threshold in plantarflexion and inversion decreased significantly in the experimental group after intervention(P<0.05).Meanwhile,after intervention,the average CAIT score,maximum ex-tension distances in the posteromedial and posterolateral directions in the mSEBT,and the ankle peak torques in plantarflexion,inversion and eversion of the experimental group were significantly higher than the control group(P<0.05),while the ankle passive motion proprioceptive threshold in plantarflex-ion was significantly lower than the latter(P<0.05).Conclusion Twelve-week simplified Tai Chi train-ing can improve the clinical subjective instability of CAI participants,maybe related to the improve-ment of ankle muscle strength,proprioception and dynamic postural stability.Therefore,it is suggest-ed that simplified Tai Chi should be one of the rehabilitation methods for CAI patients.

Objective To investigate the predictive value of color Doppler ultrasound parameters for fetal growth restriction (FGR) induced by hypertensive disorders of pregnancy in high-altitude regions. Methods Pregnant women with gestational hypertension who were treated between July 2020 and June 2022 at the Affiliated Hospital of Qinghai University (with altitude of 2, 300 meters, were divided into group A1 with 19 cases and group A2 with 51 cases according to occurrence of FGR), Yushu People's Hospital (with altitude of 3, 700 meters, were divided into group B1 with 25 cases and group B2 with 47 cases according to occurrence of FGR), and Civil Aviation Clinical Medical College of Peking University (plain region, control group with 71 cases) were enrolled in this study. All pregnant women in each group underwent fetal color Doppler ultrasound examination of the middle cerebral artery (MCA) and umbilical artery (UA) blood flow parameters, including pulsatility index (PI), resistance index (RI), systolic/diastolic ratio (S/D), peak systolicvelocity (PSV), and cerebroplacental ratio (CPR) at 28 weeks of gestation were detected. Multivariate Logistic regression analysis was performed to identify independent risk factors for FGR in pregnant women with gestational hypertension. Receiver operating characteristic (ROC) curves were plotted to analyze the predictive value of color Doppler parametersfor FGR. Results The UA blood flow parameters (PI, RI, S/D, PSV) of the fetuses in groups A1, A2, B1, and B2 were significantly higher than those in the control group, while the MCA blood flow parameters (PI, RI, S/D, PSV) and CPR were significantly lower (P < 0.05). Among the five groups, group B1 had the highest UA blood flow parameters (PI, RI, S/D, PSV) and the lowest MCA blood flow parameters (PI, RI, S/D, PSV) and CPR (P < 0.05). Multivariate Logistic regression analysis revealed that high altitude of residence and umbilical cord abnormalities were independent risk factors for FGR in pregnant women with gestational hypertension (P < 0.05). ROC curve analysis showed that the areas under the curves for the combined prediction of FGR in pregnant women with gestational hypertension at altitudes of 2, 300 meters and 3, 700 meters using color Doppler multi-parameters were 0.906 and 0.917, respectively, indicating a significantly higher predictive performance compared to individual parameter (P < 0.05). Conclusion Color Doppler ultrasound parameters of UA and MCA bloodflow during the second trimester of pregnancy demonstrate good predictive value for FGR induced by hypertensive disorders of pregnancy in high-altitude regions at different altitudes, and the predictive performance is even higher when multiple parameters are combined.

Objective To explore the diagnostic value of color Doppler ultrasound for fetal intrauterine distress(FIUD)in high-risk puerperae in plateau areas.Methods A total of 130 puerperae in plateau areas and 130 puerperae in plain areas were enrolled.According to presence or absence of FIUD in different areas,they were divided into the plateau distress group(47 cases),the plateau normal group(83 cases),the plain distress group(31 cases)and the plain normal group(99 cases).All cases underwent blood flow detection of middle cerebral artery(MCA)and umbilical artery(UA)before delivery,and cerebral-placental ratio(CPR)was calculated.The incidence of FIUD was compared between high-risk puerperae in plateau area and in plain area.Gestational age,birth weight,cesarean section rate and blood spectrum parameters of MCA and UA were compared between the four groups.The predictive value of color Doppler ultrasound parameters for FIUD was analyzed by receiver operating characteristic(ROC)curves.Results The incidence rates of FIUD and severe FIUD were higher in patients of plateau areas than those in plain areas(36.15%,13.85%vs.23.85%,4.62%,P＜0.05).Compared with the plateau distress group,gestational age and birth weight were increased in the plateau normal group and the plain distress group(P＜0.05).Compared with the plateau distress group,PI,RI,S/D and CPR of MCA were increased,while PI,RI and S/D of UA were decreased in the plateau normal group and the plain distress group(P＜0.05).Results of ROC curve analysis showed that overall performance advantage of S/D of UA was the most obvious in the diagnosis of FIUD in high-risk puerperae in plateau areas.The diagnostic sensitivity of RI of MCA was the highest,and the diagnostic specificity of CPR was the highest(P＜0.05).Conclusion Color Doppler ultrasound has good diagnostic value for FIUD in high-risk puerperae in plateau areas,which can be applied as an effective clinical screening means for FIUD.

Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity.Herein,choline metabolism was discovered by spatially resolved metab-olomics analysis as metabolic vulnerability which is highly active in different cancer types,and a choline-modified strategy for small molecule-drug conjugates(SMDCs)design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy,instead of directly inhibiting choline metabolism.As a proof-of-concept,choline-modified SMDCs were designed,screened,and investigated for their druggability in vitro and in vivo.This strategy improved tumor targeting,preserved tumor inhibition and reduced toxicity of paclitaxel,through targeted drug delivery to tumor by highly expressed choline transporters,and site-specific release by carboxylesterase.This study expands the strategy of targeting metabolic vulnerability and provides new ideas of devel-oping SMDCs for precise cancer therapy.

Objective:The aim of this study was to explore the associations of muscle size and density with handgrip strength(HGS)and the Timed Up and Go(TUG)test.Methods:Totally 301 participants living in the Xinjiekou community near Beijing Jishuitan Hospital were recruited for CT imaging of the hip and a 1-cm slice of the mid-thigh.The cross-sectional area and density of the gluteus maximus and the mid-thigh muscles were estimated by the Osirix viewer based on CT images.HGS and TUG were also performed in these subjects.Logistic regression analysis was used to evaluate the correlations of muscle density and size with TUG and grip strength.Results:In women, after adjustment for age and BMI, the density of the gluteus maximus was negatively correlated with TUG( P trend=0.0366), while the size of the gluteus maximus and the mid-thigh muscles was not correlated with TUG.In men, the density or size of these muscles was not correlated with TUG.After adjustment for age and BMI, the density of the gluteus maximus was positively correlated with grip strength( P trend=0.0334)and the size of the mid-thigh muscles was also positively correlated with grip strength( P trend=0.0155)in men, but they were not correlated with grip strength in women. Conclusions:There were sex differences in the relationship between muscle size or density and grip strength or timed up and go.The density of the gluteus maximus is associated with muscle strength and physical performance while the size of the mid-thigh muscles is correlated with muscle strength.

Objective:To explore the clinical effect of the integrated model of doctors, nurses and patients in postoperative pain nursing of patients with osteosarcoma.Methods:A total of 20 patients with osteosarcoma who underwent surgical treatment in the Department of Orthopedics of Henan Provincial People's Hospital from June 2018 to June 2019 were selected as control group, and 20 patients with osteosarcoma surgery from July 2019 to July 2020 were selected as observation group. Control group was given routine nursing, and observation group carried out the integrated nursing of doctors, nurses and patients. One day before discharge, the Satisfaction Questionnaire on Postoperative Pain Management by the Patient and the limb salvage surgery efficacy scoring system (Musculoskeletal Tumor Society, MSTS) were distributed to patients to compare patients' satisfaction with postoperative pain management, pain status and limb function between two groups.Results:The hospital stay of control group was (45.63±8.56) d, and that of observation group was (36.78±7.69) d, the difference was statistically significant ( t=7.868, P<0.01) . The most severe postoperative pain score of observation group was (3.94±1.29) , which was lower than that of control group, and the difference was statistically significant ( t=4.458, P<0.01) . The satisfaction score of observation group for the pain effect was (4.11±0.64) , which was higher than that of control group, and the difference was statistically significant ( t=4.921, P<0.05) . The total score of MSTS in observation group was (25.98±2.15) , and that of control group was (20.54±2.08) , and the difference was statistically significant ( t=8.132, P<0.01) . Conclusions:The integrated model of doctors, nurses and patients can improve the satisfaction of perioperative pain management of patients with osteosarcoma, reduce the level of pain, and improve the level of limb function of patients.

Microbes play important roles in human health and disease. The interaction between microbes and hosts is a reciprocal relationship, which remains largely under-explored. Current com-putational resources lack manually and consistently curated data to connect metagenomic data to pathogenic microbes, microbial core genes, and disease phenotypes. We developed the MicroPhenoDB database by manually curating and consistently integrating microbe-disease associ-ation data. MicroPhenoDB provides 5677 non-redundant associations between 1781 microbes and 542 human disease phenotypes across more than 22 human body sites. MicroPhenoDB also pro-vides 696,934 relationships between 27,277 unique clade-specific core genes and 685 microbes. Dis-ease phenotypes are classified and described using the Experimental Factor Ontology (EFO). A refined score model was developed to prioritize the associations based on evidential metrics. The sequence search option in MicroPhenoDB enables rapid identification of existing pathogenic microbes in samples without running the usual metagenomic data processing and assembly. Micro-PhenoDB offers data browsing, searching, and visualization through user-friendly web interfaces and web service application programming interfaces. MicroPhenoDB is the first database platform to detail the relationships between pathogenic microbes, core genes, and disease phenotypes. It will accelerate metagenomic data analysis and assist studies in decoding microbes related to human dis-eases. MicroPhenoDB is available through http://www.liwzlab.cn/microphenodb and http://lilab2. sysu.edu.cn/microphenodb.