Ten ursolic acid derivatives were designed from the lead compound ursolic acid by introducing 1,2,3-triazole at C-3 and C-28. The target compounds were synthesized and characterized by ¹H NMR and ¹³C NMR. MTT assay was used to study the antitumor activity of these compounds in human cancer cells with high expression (MCF-7 and SGC-7901). The results showed that the antitumor activity of all compounds on MCF-7 and SGC-7901 tumor cells was significantly higher than that of ursolic acid. The compound II₄ exhibited significant antitumor activity which was equivalent to the positive control drug nilotinib, molecular docking showed that the compound II₄ have high binding ability with c-Kit, which deserves further research.

Objective To explore the effect of Polysaccharides of Panax notoginseng(PPN)on anti-exercise fatigue in mice.Methods One hundred male KM mice were randomly divided into negative control group,positive control group and experimental-L,-M,-H groups,with 20 cases per group.Experimental-L,-M,-H groups was given 100,200,400 mg·kg-1 PPN,respectively;positive control group was given 200 mg·kg-1 vitamin C;negative control group was given 0.1 mL·10 g-1 0.9％NaCl.Five groups were gavaged once a day for 28 days.After the last administration,the loaded swimming time was measured;after 90 minutes of the unloaded swimming test,the mice were allowed to rest for 30 minutes,the levels of lactic acid(LD),blood urea nitrogen(BUN),glycogen,and malondialdehyde(MDA)were measured,the safety of PPN with organ indices and histopathology.Results LD levels in negative control group,positive control group and experimental-L,-M,-Hgroupswere(4.76±0.84),(2.86±0.34),(3.00±0.69),(2.35±0.65)and(1.39±0.48)mg·kg-1;BUN contents were(13.65±1.25),(12.55±0.91),(12.12±1.24),(11.06±1.30)and(9.85±1.05)mmol·L-1;liver glycogen contents were(3.24±0.56),(11.11±2.16),(5.61±1.41),(6.60±1.49)and(12.05±2.25)mg·g-1;MDA levels were(2.36±0.21),(1.23±0.41),(1.93±0.23),(1.73±0.21)and(1.04±0.18)mg prot·mL-1.Compared with negative control group,the differences of above indexes in the positive control group and experimental-L,-M,-H groups were statistically significant(P＜0.05,P＜0.01,P＜0.001).Conclusion PPN can increase exercise endurance in mice and has an anti-fatigue effect.This study provides a theoretical basis for the application of PPN in the field of anti-fatigue research.

Objective To explore the effect of phillyrin(KD-1)on lung injury in rats with influenza virus pneumonia and its regulatory mechanism on the sphingosine kinases 1(SphK1)/sphingosine 1-phosphate(S1P)/S1P receptors 1(S1PR1)signal pathway.Methods Wistar male rats were divided into control group(gavage with equal amount of 0.9％NaCl),model group(gavage with equal amount of 0.9％NaCl),positive drug group(gavage with 0.02 g·kg-1 ribaverin),PF-543 group(gavage with 10 mg·kg-1 SphK1 inhibitor PF-543 Citrate)and experimental-L,-H groups(gavage with 6.5,13 mg·kg-1 KD-1,respectively).Except the control group,the other rats were treated with influenza virus nasal drip to establish influenza virus infection pneumonia model.The lung index of rats was measured;Hematoxylin-eosin(HE)staining was applied to observe the pathological damage of lung tissue in rats;the contents of interleukin 1β(IL-1β),tumor necrosis factor α(TNF-α)and IL-6 in bronchoalveolar lavage fluid(BALF)were detected by enzyme linked immunosorbent assay(ELISA);Western blot was applied to detect the expression levels of SphK1,S1P and S1PR1 proteins in rat lung tissue.Results The lung indices of experimental-L,-H groups,PF-543 group,positive drug group,model group and control group were(7.62±0.51),(5.34±0.46),(6.53±0.52),(5.48±0.43),(12.46±0.87)and(4.41±0.32)mg·g-1;IL-1β content were(47.26±2.05),(25.18±1.58),(35.75±1.50),(27.31±1.67),(62.37±2.51)and(13.28±1.04)ng·L-1;the contents of TNF-α were(76.58±4.73),(51.82±3.90),(64.81±4.15),(53.06±3.86),(98.47±4.92)and(42.71±3.52)ng·L-1;IL-6 content were(57.62±4.29),(39.06±3.86),(48.75±3.83),(41.23±3.61),(76.92±5.24)and(28.56±3.17)ng·L-1;SphK1 protein expression were 1.07±0.08,0.51±0.04,0.65±0.05,0.53±0.04,1.28±0.09 and 0.36±0.03;S1P protein expression were 1.21±0.10,0.57±0.05,0.73±0.06,0.58±0.05,1.39±0.11 and 0.39±0.03;S1PR1 protein expression were 0.45±0.03,0.83±0.07,0.64±0.05,0.81±0.07,0.28±0.02 and 1.03±0.07,respectively.Compared with the control group,the above indexes in the model group had statistical significance(all P＜0.05);compared with the model group,the above indexes in experimental-L,-H groups,PF-543 group and positive drug group had statistical significance(all P＜0.05).Conclusion KD-1 may alleviate lung injury in rats with influenza virus pneumonia by inhibiting the SphK1/S1 P/S1 PR1 signal pathway.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To study the antioxidant activity and organ protection of different components of Panax notoginseng polysaccharide(PNPS)in D-galactose-induced oxidative damage aging model mice.Methods KM mice were randomly divided into normal group,model group,vitamin C(VC)group(given 200 mg·kg-1 VC),crude polysaccharide from Panax notoginseng(CPPN)group,neutral polysaccharide from Panax notoginseng(NPPN)group and acidic polysaccharide from Panax notoginseng(APPN-Ⅰ,APPN-Ⅱ,APPN-Ⅲ)group(given 400 mg·kg-1 CPPN,NPPN,APPN-Ⅰ,APPN-Ⅱ,APPN-Ⅲ,respectively).Except for the normal group,oxidative injury aging mouse models were established by intraperitoneal injection of 1 g·kg-1 D-galactose.The mice were sacrificed after continuous administration for 42 days,and serum and liver homogenate were prepared.Malondialdehyde(MDA)was determined by thiobarbituric acid method;superoxide dismutase(SOD)was determined by tetrazole salt method;glutathione peroxidase(GSH-Px)was determined by double antibody sandwich method.Results Serum SOD in the normal group,model group,VC group,CPPN group,NPPN group and APPN-Ⅰ,APPN-Ⅱ,APPN-Ⅲ groups were(15.07±0.69),(12.79±1.51),(15.56±1.01),(13.69±0.96),(14.27±0.64),(14.31±0.99),(14.18±0.79)and(15.85±0.89)U·mL-1;serum GSH-Px were(105.35±4.97),(90.36±4.31),(111.51±7.00),(113.03±8.06),(118.77±5.19),(123.60±8.08),(131.65±3.60)and(149.22±13.32)ng·L-1;serum MDA were(1.72±0.26),(4.16±0.92),(2.26±0.59),(2.82±0.47),(2.46±0.50),(1.98±0.41),(2.39±0.39)and(2.07±0.24)nmol·mL-1;the liver SOD were(234.22±3.84),(205.04±7.28),(234.63±6.37),(214.99±17.66),(234.13±3.63),(234.63±3.44),(233.87±5.63)and(235.42±2.33)U·mgprot-1;liver GSH-Px were(274.27±23.72),(207.00±15.22),(257.68±16.39),(249.79±18.78),(252.62±10.92),(256.25±21.83),(261.20±17.52)and(263.16±17.98)ng·L-1;liver MDA were(35.70±3.52),(49.65±6.32),(36.15±2.48),(39.17±4.29),(37.40±6.19),(35.34±4.06)and(35.90±5.36),(33.31±7.64)nmol·mgprot-1.Compared with the normal group,SOD,GSH-Px in serum and liver of mice in the model group were significantly reduced,and the content of MDA was significantly increased(all P＜0.01).After treatment with different components of Panax notoginseng polysaccharide,the oxidative indicators in mice were significantly improved,among which APPN-Ⅲ have the best antioxidant activity,which could significantly increase the activities of SOD,GSH-Px in serum and liver,and reduce the content of MDA(all P＜0.01).Conclusion Different components of Panax notoginseng polysaccharide have antioxidant activity and organ protection in vivo,among which APPN-Ⅲ has the best antioxidant activity and has a good organ protection effect.

ObjectiveThe scale of microalgae farming industry is huge. During farming, it is easy for microalgae to be affected by miscellaneous bacteria and other contaminants. Because of that, periodic test is necessary to ensure the growth of microalgae. Present microscopy imaging and spectral analysis methods have higher requirements for experiment personnel, equipment and sites, for which it is unable to achieve real-time portable detection. For the purpose of real-time portable microalgae detection, a real-time microalgae detection system of low detection requirement and fast detection speed is needed. MethodsThis study has developed a microalgae detection system based on deep learning. A microscopy imaging device based on bright field was constructed. With imaged captured from the device, a neural network based on YOLOv3 was trained and deployed on microcomputer, thus realizing real-time portable microalgae detection. This study has also improved the feature extraction network by introducing cross-region residual connection and attention mechanism and replacing optimizer with Adam optimizer using multistage and multimethod strategy. ResultsWith cross-region residual connection, the mAP value reached 0.92. Compared with manual result, the detection error was 2.47%. ConclusionThe system could achieve real-time portable microalgae detection and provide relatively accurate detection result, so it can be applied to periodic test in microalgae farming.

The purpose of this study was to enrich the genomic information and provide a basis for further development and utilization of Polygonatum kingianum. The fresh rhizome of P. kingianum was used as the experimental material, and the full-length transcriptome was sequenced by PacBio Sequel platform. The final measured polymerase reads were 1 120 485, with a total of 77.73 GB of data. In NR database, 41 864 homologous sequence alignments were aligned to 5 species; 40 506 were annotated in the KOG database and classified into 26 categories based on their functionality; 69 060 GO annotated 32 functional groups divided into 3 categories: cellular components, molecular functions, and biological processes; 45 779 annotations were added to 145 metabolic pathways in the KEGG database. Among them, there are 127 identified transcripts related to polysaccharide synthesis in the glycolysis/gluconeogenesis metabolic pathway, 144 in the starch and sucrose metabolic pathway, 85 in the amino acid sugar and nucleotide sugar metabolic pathway, and 69 in the fructose and mannose metabolic pathway. In addition, 1 781 transcription factors were detected, distributed in 37 transcription factor families; 180 293 SSR loci were detected, among which single base repeats accounted for the most, accounting for 30.48% of all base repeats, and at least five base repeats, accounting for only 0.14% of single base repeats. The results of this study provide important data supporting for enriching the genomic information of P. kingianum and exploring its effective biosynthetic pathway.

This paper applied gas chromatography-mass spectrometry (GC-MS), network pharmacology and nuclear magnetic resonance hydrogen spectroscopy (¹H NMR) metabolomics techniques to study the material basis and mechanism of action of Ning Shen Essential Oil in anti-insomnia. The main volatile components of Ning Shen Essential Oil were analyzed by gas chromatography-mass spectrometry (GC-MS), and the insomnia-related targets were predicted using the Traditional Chinese Medicine Systematic Pharmacology Database and Analytical Platform (TCMSP) and the databases of GeneCards, OMIM and Drugbank. The insomnia model of rats was replicated by intraperitoneal injection of 4-chloro-DL-phenylalanine (PCPA). Animal experiments were approved by the Animal Ethics Committee of Shandong University of Traditional Chinese Medicine (Ethics No.: SDUTCM20221025010). The modulating effect of Compound Ning Shen Essential Oil on anxiety behavior of rats was evaluated by behavioral related indexes. The serum levels of corticotropin-releasing hormone (CRH), adrenotropic corticotropic hormone (ACTH) and melatonin (MT) were measured by enzyme-linked immunoassay (ELISA). Rat serum and hippocampus were taken for nuclear magnetic resonance (¹H NMR) metabolomics to detect the changes of endogenous metabolites in rat serum hippocampus, to designate the differential metabolites and to construct metabolic pathways. The results showed that the exercise distance in the open field experiment and the number of times and time to enter the open arm in the elevated cross maze experiment of the rats in the model group were significantly reduced (P < 0.05, P < 0.01). The behavioral indexes of rats improved to different degrees after the administration of Ning Shen Essential Oil. The serum CRH and ACTH levels of rats in the model group increased significantly (P < 0.05, P < 0.01), and the MT level decreased significantly (P < 0.01); After the intervention, serum CRH and ACTH levels were reduced to different degrees, and MT levels could be regressed. ¹H NMR metabolomics screened 10 potential biomarkers related to insomnia, which involved in 6 potential metabolic pathways. A total of 35 components of Ning Shen Essential Oil were detected by GC-MS, the main component targets of Ning Shen Essential Oil and insomnia disease targets were intersected, a total of 172 intersecting genes were screened, and 26 core targets were identified. The study demonstrated that Ning Shen Essential Oil had protective effects against PCPA-induced insomnia in rats, which was probably correlated with regulation of the hypothalamic-pituitary-adrenal axis (HPA) related hormones and metabolism of amino acids, lipids and choline.

The incidence of intrahepatic cholangiocarcinoma (ICC) continues to rise, and there are no effective drugs to treat it. The immune microenvironment plays an important role in the development of ICC and is currently a research hotspot. Icaritin (ICA) is an innovative traditional Chinese medicine for the treatment of advanced hepatocellular carcinoma. It is considered to have potential immunoregulatory and anti-tumor effects, which is potentially consistent with the understanding of "Fuzheng" in the treatment of tumor in traditional Chinese medicine. However, whether ICA can be used to treat ICC has not been reported. Therefore, in this study, sgp19/kRas, an in situ ICC mouse model with intact immune system, was selected to evaluate the efficacy of ICA in the treatment of ICC in vivo for the first time, and the effects of ICA on the tumor immune microenvironment of ICC mice were analyzed by flow cytometry. This experiment was approved by the Experimental Animal Ethics Committee of Capital Medical University (approval number: AEEI-2023-138). In this study, sgp19/kRas ICC mouse model was treated with oral gavage of 100 mg·kg^-1 ICA. We found that ICA significantly inhibited tumor growth and tumor cell proliferation in the sgp19/kRas ICC mouse model after 3 weeks of treatment. Flow cytometry analysis indicated that ICA treatment markedly reduced the proportion of M2 macrophages and increased the number of CD3⁺CD4⁺ T cells. In vitro experiments demonstrated that ICA promoted macrophage polarization towards the M1 phenotype while inhibiting polarization towards the M2 phenotype. Furthermore, transcriptomic analysis suggested that ICA enhanced Toll-like receptor 9 (TLR9) expression, influencing macrophage nitric oxide metabolism synthesis pathways and receptor-related activities, thereby regulating macrophage polarization. In summary, this study demonstrates that ICA treatment significantly delays tumor progression in sgp19/kRas ICC mouse models. Mechanistically, ICA may achieve its anti-ICC effects by upregulating TLR9 receptor expression levels, promoting macrophage polarization towards the M1 phenotype, and altering the tumor immune microenvironment.

Fluorescence anisotropy(FA)analysis has many advantages such as no requirement of separation,high throughput and real-time detection,and thus has been widely used in many fields,including biochemical analysis,food safety detection,environmental monitoring,etc.However,due to the small volume or mass of the target,its combination with the fluorescence probe cannot produce significant signal change.To solve this issue,researchers often use nanomaterials to enhance the mass or volume of fluorophore to improve the sensitivity.Nevertheless,this FA amplification strategy also has some disadvantages.Firstly,nanomaterials are easy to quench fluorescence.As a result,the FA value is easily influenced by light scattering,which reduces the detection accuracy.Secondly,fluorescent probes in most methods require complex modification steps.Therefore,it is necessary to develop new FA probes that do not require the amplification of volume and mass or modification.As a new kind of nanomaterials,luminescent metal-organic framework(MOF)has a large volume(or mass)and strong fluorescence emission.It does not require additional signal amplification materials.As a consequence,it can be used as a potential FA probe.This study successfully synthesized a lanthanide metal organic framework(Ce-TCPP MOF)using cerium ion(Ce3+)as the central ion and 5,10,15,20-tetra(4-carboxylphenyl)porphyrin(H2TCPP)as the ligand through microwave assisted method,and used it as a novel unmodified FA probe to detect phosphate ions(Pi).In the absence of Pi,Ce-TCPP MOF had a significant FA value(r).After addition of Pi,Pi reacted with Ce3+in MOF and destroyed the structure of MOF into the small pieces,resulting in a decrease in r.The experimental results indicated that with the increase of Pi concentration,the change of the r of Ce-TCPP MOF(Δr)gradually increased.The Δr and Pi concentration showed a good linear relationship within the range of 0.5-3.5 μmol/L(0.016-0.108 mg/L).The limit of detection(LOD,3σ/k)was 0.41 μmol/L.The concentration of Pi in the Jialing River water detected by this method was about 0.078 mg/L,and the Pi value detected by ammonium molybdate spectrophotometry was about 0.080 mg/L.The two detection results were consistent with each other,and the detection results also meet the ClassⅡwater quality standard,proving that this method could be used for the detection of Pi in complex water bodies.