Isolating Antipathogenic Fungal Coumarins from Coriaria nepalensis and Determining Their Primary Mechanism In Vitro.

Through bioassay-guided isolation, eight undescribed coumarins (1-8), along with six reported coumarins (9-14), were obtained from Coriaria nepalensis. The new structures were determined by using IR, UV, NMR, HRESIMS, and ECD calculations. The results of the biological activity assays showed that compound 9 exhibited broad spectrum antifungal activities against all tested fungi in vitro and a significant inhibitory effect on Phytophthora nicotianae with an EC50 value of 3.00 µg/mL. Notably, compound 9 demonstrated greater curative and protective effects against tobacco balack shank than those of osthol in vivo. Thus, 9 was structurally modified to obtain new promising antifungal agents, and the novel derivatives (17b, 17j, and 17k) exhibited better effects on Sclerotinia sclerotiorum than did lead compound 9. Preliminary mechanistic exploration illustrated that 9 could enhance cell membrane permeability, destroy the morphology and ultrastructure of cells, and reduce the exopolysaccharide content of P. nicotianae mycelia. Furthermore, the cytotoxicity results revealed that compound 9 exhibited relatively low cytotoxicity against HEK293 cell lines with an inhibition rate of 33.54% at 30 µg/mL. This research is promising for the discovery of new fungicides from natural coumarins with satisfactory ecological compatibility.

Four new pregnane C21 steroids isolated from the roots of Cynanchum auriculatum.

Four new steroids cynansteroid G-I (1-3) and cynansteroid K (4), a new natural product 5,6-deacidizingcaudatin (5), and a known compound glycocaudatin (6), were isolated from the roots of Cynanchum auriculatum. The structures of new compounds were identified by comprehensive spectroscopic analyses, including NMR, HRESI-MS, ECD, UV, and IR spectral data. The cytotoxic activities of all the isolates against two human tumour cell lines (COLO-205 and BGC-823) were screened, unfortunately, which were weaker than positive control.

Synthesis and Antifungal Activity of 2-(2-Benzoxazolyl)-1-arylethanone and 2-(2-Benzoxazolyl)-1-alkylethanone Derivatives.

To discover more effective antifungal candidates, 33 benzoxazole derivatives, were designed, synthesized, and evaluated for their antifungal activity against seven phytopathogenic fungi by the mycelium growth rate method. Among 33 benzoxazole derivatives had thirteen derivatives no reported, and new derivatives C17 exhibited good inhibitory activity against Phomopsis sp. with EC50 values of 3.26 µM. Structure-activity relationship (SAR) of these derivatives analysis indicated that the substituent played a key role in antifungal activity in ortho-, meta- and para- substituted acetophenones. The preliminary mechanistic exploration demonstrated that C17 might exert its antifungal activity by targeting the mycelia cell membrane, which was verified by the observed changes in mycelial morphology, the formation of extracellular polysaccharides, cellular contents, cell membrane permeability and integrity, among other effects. Furthermore, C17 had potent curative effect against Phomopsis sp. in vivo, which indicated that C17 may be as a novelty potent antifungal agent.

Bidirectional causal relationship between depression and frailty: a univariate and multivariate Mendelian randomisation study.

BACKGROUND: cumulative evidence from cohort studies suggested that there were inconsistent conclusions as to whether there was a bidirectional association between depression and frailty. Therefore, this study used a bidirectional two-sample Mendelian randomisation (MR) study to investigate the causal relationship between depression and frailty. METHODS: we performed univariate and multivariate bidirectional MR analyses to assess the causal association between depression and frailty. Independent genetic variants associated with depression and frailty were selected as instrumental variables. Inverse variance weighted (IVW), MR-Egger, weighted median and weighted mode were mainly used in univariate MR analysis. Multivariate MR (MVMR) analyses used multivariable inverse variance-weighted methods to individually and jointly adjust for three potential confounders, body mass index (BMI), age at menarche (AAM) and waist-to-hip ratio (WHR, adjusted for BMI). RESULTS: univariate MR analysis showed a positive causal relationship between depression and risk of frailty (IVW, odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.23-1.37, P = 6.54E-22). Causal relationship between frailty and risk of depression (IVW, OR = 1.69, 95% CI = 1.33-2.16, P = 2.09E-05). MVMR analysis revealed that the bidirectional causal association between depression and frailty remained after adjusting for three potential confounders, BMI, AAM and WHR (adjusted for BMI), individually and in combination. CONCLUSIONS: our findings supported a causal relationship between genetically predicted depression and frailty in both directions.

Synthesis and Antifungal Activity of Curcumol Derivatives.

To discover novel and effective antifungal candidates, a series of new curcumol derivatives were designed, synthesized, and evaluated their antifungal activity against five phytopathogenic fungi by the mycelium growth rate method. Derivatives c4, c22 and c23 exhibited excellent antifungal activity against Phomopsis sp. with EC50 values of 3.06, 3.07, and 3.16 µM, respectively. Specifically, compound c4 exhibited the strongest antifungal activity against Phomopsis sp., which was 44 times that of pyrimethanil (EC50 =134.37 µM). The results of scanning electron microscopy (SEM) and transmission electron microscopy (TEM) indicated that compound c4 could cause cell senescence and death of Phomopsis sp. by changing the normal hyphal morphology and disrupting the normal metabolism of hyphal cells. Moreover, compound c4 showed excellent curative effect against Phomopsis sp. on kiwifruit. These findings confirmed that compound c4 has great potential as a potent antifungal agent.

Chemical Constituents of Primulina eburnea (Gesneriaceae) and Their Cytotoxic Activities.

Two new ursane-type triterpenes, eburnealactones A and B (1 and 2), one new flavonoid, eburneatin A (6), and one new phenylethanoid glycoside, chiritoside D (7), along with 9 known compounds (3-5, 8-13) were isolated from the whole plant of Primulina eburnea. Their structures were elucidated by comprehensive spectroscopic data analysis (IR, UV, NMR, and HR-ESI-MS). All the compounds were evaluated for their cytotoxic activities. Compound 1 showed significant cytotoxic activities against MKN-45 cell lines and 5637 cell lines with the IC50 values of 9.57 µM and 8.30 µM, respectively. Compound 1 exhibited moderate cytotoxic activities against A549 and PATU8988T cell lines with the IC50 values of 30.70 µM and 38.22 µM, respectively. Compound 6 exhibited moderate cytotoxic activities against MKN-45, HCT116, PATU8988T, 5637 and A-673 cell lines with the IC50 values of 19.69 µM, 16.44 µM, 18.07 µM, 11.51 µM and 18.15 µM, respectively. Compound 5 showed moderate cytotoxic activities against A549 cell lines with the IC50 values of 24.06 µM.

Quinoline Alkaloids from the Roots of Orixa japonica with the Anti-Pathogenic Fungi Activities.

A new quinoline alkaloid, 5-hydroxy-6-methoxy-N-methyl-2-phenylquinoline-4-one (1), and seventeen known quinoline alkaloids (2-18) were isolated from the roots of Orixa japonica. The structure of 1 was determined by analysis of spectroscopic data. Among them, compounds 2, 3, and 13 were isolated from this plant for the first time. All isolates were screened for the anti-pathogenic fungi activities, including Rhizoctonia solani, Magnaporthe oryzae, and Phomopsis sp. The results showed that five compounds (4, 8, 10, 11, and 12) exhibited significant anti-pathogenic fungi effects at 50.0 µg/mL. In special, compound 10 exhibited the best antifungal activities toward R. solani and M. oryzae with the IC50 values of 37.86 and 44.72 µM, respectively, better than that of the positive control, hymexazol (IC50 121.21 and 1518.18 µM, respectively). Moreover, eleven new quinoline alkaloids derivatives (12a-12k) were designed and synthesized to investigate the structure-activity relationships (SARs). The SARs analysis indicated that the furo[2,3-b]quinoline skeleton and the methoxy at C-7 (compounds 8, 11, and 12) played a key role for improving the antifungal activities.

Event-related potential response to drivers' facial expressions in an online car-hailing scene.

Recognizing facial expressions is crucial for adaptive social interaction. Prior empirical research on facial expression processing has primarily focused on isolated faces; however, facial expressions appear embedded in surrounding scenes in everyday life. In this study, we attempted to demonstrate how the online car-hailing scene affects the processing of facial expression. This study examined the processing of drivers' facial expressions in scenes by recording event-related potentials, in which neutral or happy faces embedded in online car-hailing orders were constructed (with type of vehicle, driver rating, driver surname, and level of reputation controlled). A total of 35 female volunteers participated in this experiment and were asked to judge which facial expressions that emerged in scenes of online car-hailing were more trustworthy. The results revealed an interaction between facial expression scenes, brain areas, and electrode sites in the late positive potential, which indicated that happy faces elicited larger amplitudes than did neutral ones in the parietal areas and that scenes with happy facial expressions had shorter latencies than did those with neutral ones. As expected, the late positive potential evoked by happy facial expressions in a scene was larger than that evoked by neutral ones, which reflected motivated attention and motivational response processes. This study highlights the importance of scenes as context in the study of facial expression processing.

The value of plasma insulin-like growth factor 1 and interleukin-18 in the diagnosis of bronchopulmonary dysplasia in premature infants.

Objective: To explore the diagnostic value of IGF-1 and IL-18 in premature infants with BPD. Methods: Through a prospective observational study, the serum samples of infants in the BPD group and the non-BPD group were collected at different targeted time points, and the serum IGF-1 and IL-18 concentrations were dynamically monitored by ELISA. The Student t-test and one-way analysis of variance were adopted to analyze data, and the receiver operating characteristic (ROC) curve was used to test the diagnostic value. Result: A total of 90 VLBW premature infants admitted to NICU between January 2020 and 2021 were finally included. Compared with the non-BPD group, infants diagnosed with BPD had a significantly lower serum concentration of IGF-1 (P < 0.05) but a higher level of IL-18 (P < 0.05) on days 1, 7, 14, and 28 after birth. With the ROC curve analysis, the serum concentration IGF-1 on day 14 and IL-18 on day 28 reported high sensitivity and specificity to predict the risk of BPD (IGF-1: sensitivity: 89.29%, specificity: 77.78%, AUC: 0.8710; IL-18: sensitivity: 53.57%, specificity: 83.33%, AUC: 0.7887). And more substantial predictive power was found in combined analysis of IGF-1 and serum IL-18 on day 14: the sensitivity was 91.07% and the specificity was 83.33%, with the AUC of 0.9142. Conclusion: IGF-1 and IL-18 might be closely involved in the occurrence and development of BPD. The serum concentration of IGF-1 combined with IL-18 could be potentially sensitive markers for the early diagnosis and severity of BPD.

Maillard Reaction Products with Anti-Tobacco Mosaic Virus Activities Generated in Processed Thermopsis lanceolata R. Br. Seed Extract.

Six novel Maillard reaction products (MRPs) (1-6) were isolated from the processed Thermopsis lanceolata R. Br. seed extract, along with one biogenetically related intermediate (7). Compounds 1-4 possessed three rare dimerization patterns constructed by cytisine, whereas compounds 5 and 6 represented the first example of the addition products of cytisine and 5,6-dihydroxy-4-hexanolide. Their structures were elucidated by comprehensive spectroscopic data analysis and quantum chemistry calculations including GIAO 13C{1H} NMR and ECD calculation, combined with single-crystal X-ray diffraction analysis. Biologically, compound 3 displayed significant anti-tobacco mosaic virus activity compared with the positive control ningnanmycin.

Desorption Electrospray Ionization Mass Spectrometry Imaging Illustrates the Quality Characters of Isatidis Radix.

For a long history, herbal medicines have made significant contributions to human health all around the world. However, the exploration of an effective approach to illustrate their inner quality remains a challenge. So, it is imperative to develop new methods and technologies to characterize and identify quality markers of herbal medicines. Taking Isatidis Radix, the dried root of Isatis indigotica as an example, desorption electrospray ionization (DESI), in combination with quadrupole-time-of-flight mass spectrometry (Q-TOF/MS), was applied in this work for the first time to reveal the comprehensive spatial distribution of metabolites and, further, to illustrate quality characters of this herbal medicine. After simple pretreatment, 102 metabolites including alkaloids, sulfur-containing compounds, phenylpropanoids, nucleosides, amino acids, organic acids, flavonoids, phenols, terpenes, saccharides, peptides, and sphingolipids were characterized, some of which were successfully localized and visualized in the transverse section of the root. Based on the ion images, samples with different quality characters were distinguished unambiguously by the pattern recognition method of orthogonal partial least squares discrimination analysis (OPLS-DA). Simultaneously, 11 major influencing components exerting higher ion intensities in superior samples were identified as the potential quality markers of Isatidis Radix. Desorption electrospray ionization (DESI) mass spectrometry imaging (MSI), together with chemometric analysis could not only improve the understanding of the plant biology of herbal medicines but also be beneficial in the identification of quality markers, so as to carry out better quality control of herbal medicines.

Analysis of diagnosing neonatal respiratory distress syndrome with lung ultrasound score.

Objectives: To investigate the diagnostic effect of lung ultrasound on neonatal respiratory distress syndrome (NRDS) and to analyze the clinical application value of pulmonary ultrasound score. Methods: Sixty-five NRDS babies who were diagnosed in our hospital from August 2019 to October 2020 were selected as the observation group, and 65 healthy babies were selected as the control group. Children in the two groups underwent lung ultrasound examination. The characteristic signs of lung ultrasound in the two groups were analyzed, and the detection rate of various signs and lung ultrasound score were compared between the two groups. Results: The main manifestations of lung ultrasound in NRDS children were pulmonary parenchyma, abnormal pleural line, blurred or disappeared A line, pleural effusion, white lung, and weak or disappeared pulmonary pulsation; the lung ultrasound scores of different positions in the observation group were higher than those in the control group, and the differences were statistically significant (P<0.05). The detection rates of signs such as lung parenchyma, abnormal pleural line, disappeared A line, diffuse pulmonary edema, and air bronchogram in the observation group were significantly higher than that in the control group (P<0.05), and there was no significant difference in the detection rate of the sign of B line existence between the two groups (P>0.05). Conclusion: Lung ultrasound has a high diagnostic value in diagnosing NRDS, and lung ultrasound score can evaluate the severity of NRDS in babies to further optimize the diagnosis results, which has important clinical significance.

Three New Pregnanes Isolated from the Cynanchum auriculatum.

Three new compounds named cynansteroid A (1), cynansteroid B (2) and cynansteroid C (3), together with nine known C21 -steroidal pregnane sapogenins (4-12) were isolated from the hydrolytic extract of the roots of Cynanchum auriculatum. The structures of cynansteroid A-C (1-3) were ascertained via the detailed analysis of the HR-ESI-MS, 1D and 2D NMR, and the calculated and experimental ECD data of cynansteroid B (2). Compound 11 displayed moderate inhibitory activity toward Verticillium dahliae Kleb (IC50 =37.15 µM), furthermore, compounds 11 and 12 showed significant inhibitory activity against Phomopsis sp. (IC50 =16.49 µM and 17.62 µM, respectively).

The risk factors of preterm birth: A multicentre case-control survey in China in 2018.

OBJECTIVES: To investigate the risk profile of preterm birth (PTB) in 2018 in China. METHOD: A prospective multicentre case-control study was conducted in 15 hospitals located in seven provinces throughout three geographical areas (the Eastern, South-Central and North-Western regions) in China. A total of 3147 preterm (<37+0 weeks) and 3147 term (37+0 to 41+6 weeks) live-birth mothers were included. Designed questionnaires were used to investigate maternal and fetal information. We calculated multivariable logistic regression and population attributable risk (PAR). RESULTS: Iatrogenic PTB accounted for 48.1% of preterm mothers. Multivariable analysis showed PTB was significantly associated with six categories of maternal and fetal factors, adverse life-style and psychological conditions (adjusted odds ratio (aOR) 2.063, 95% confidence interval (CI) 1.601-2.657) had the highest PAR% (60.1%). High school and below education level (PAR% = 25.8%), living in town or village (PAR% = 24.4%), low pregnant weight gain (PAR% = 16.8%), hypertensive disorders in pregnancy (aOR: 5.010, 95% CI: 4.039-6.216, PAR% = 15.3%), placental abnormality (aOR: 4.242, 95% CI: 3.454-5.211, PAR% = 14.1%) and multiple pregnancy (aOR: 10.990, 95% CI: 7.743-15.599, PAR% = 11.8%) were significantly associated with PTB with high PAR% value. CONCLUSION: The main risk factors for PTB in China were placental abnormality, hypertensive disorders in pregnancy and multiple pregnancy. Adverse life-style and psychological conditions and socio-economic disadvantage had high public health significance.

Thermlanseedlines A-G, seven thermopsine-based alkaloids with antiviral and insecticidal activities from the seeds of Thermopsis lanceolata R. Br.

Seven undescribed thermopsine-based alkaloids (1-7), including one undescribed biogenetically related intermediate (7), were isolated from the seeds of Thermopsis lanceolata R. Br. Compound 1 possessed a 6/6-6 tricyclic skeleton, while compounds 2-6 represented three rare dimerization patterns constructed by quinolizidine alkaloids. Their structures were elucidated by comprehensive spectroscopic data analysis as well as ECD calculations. Biologically, compound 6 displayed significant anti-Tomato spotted wilt virus (TSWV) activity compared with the positive control ningnanmycin. Moreover, compound 1 exhibited good insecticidal activity against Aphis fabae with LC50 value of 25.2 mg/L.

Oreocharioside A-G, new acylated C-glycosylflavones from Oreocharis auricula (Gesneriaceae).

Seven new acylated C-glycosylflavones, oreocharioside A-G, together with two known compounds were isolated from the whole plant of Oreocharis auricula. Their structures were characterized by the comprehensive analysis of their NMR, IR, UV, CD spectra and HRESIMS data. All the new compounds were evaluated for the antioxidant and anti-inflammatory activities. The results showed that compounds 1 and 2 had significant DPPH and ABTS radical scavenging activities, with the IC50 values of 0.32-3.20 µg/mL. Compounds 2 and 3 exhibited the higher potency among all the new compounds in reducing TNF-α production.

Two new cytisine-type alkaloids from the seeds of Thermopsis lanceolata.

Two new (1 and 2) cytisine-type alkaloids that were chemically inseparable isomers (present in a 1:1 ratio) were identified from the seeds of Thermopsis lanceolata R. Br. Their structures were elucidated by comprehensive spectroscopic data analysis (IR, UV, NMR, HRESIMS) and ECD calculation. Compound 1 displayed significant anti-tobacco mosaic virus (TMV) activity, while compounds 1 and 2 displayed moderate insecticidal activities against Aphis fabae with LC50 value of 43.15 and 46.47 mg/L, respectively.

Chemical constituents from the flowers of Hypericum monogynum L. with COX-2 inhibitory activity.

Hypericum monogynum L. (Hypericaceae) has been used as a folk Chinese medicine for the treatment of inflammatory related diseases. Cyclooxygenase-2 (COX-2) is a crucial target for the development of agents to treat inflammation. To search for anti-inflammatory compounds from traditional Chinese medicines, a chemical constituent study along with COX-2 inhibitory activity analysis was performed for this plant. In this study, sixteen chemical monomers, including three undescribed oxidative degradation polycyclic polyprenylated acylphloroglucinols (PPAPs, hypemoins C-E), two undescribed PPAPs (hypemoins A and B), and 11 known compounds, were identified from the flowers of H. monogynum. Their structures were characterized by HRESIMS, NMR techniques, ECD, and single crystal X-ray diffraction. Four flavonoid derivatives showed remarkable COX-2 inhibitory activities, with IC50 values ranging from 0.220 ± 0.006 to 1.655 ± 0.098 µM. Among these compounds, the possible recognition mechanism between quercetin 3-(6″-O-caffeoyl)-ß-3-D-galactoside and COX-2 was predicted by molecular docking analysis. Moreover, the multidrug resistance reversal activities for the selected compounds were evaluated.

Microscopic Mass Spectrometry Imaging Reveals the Distribution of Phytochemicals in the Dried Root of Isatis tinctoria.

The dried root of Isatis tinctoria L. (Brassicaceae) is one of the most popular traditional Chinese medicines with well-recognized prevention and treatment effects against viral infections. Above 300 components have been isolated from this herb, but their spatial distribution in the root tissue remains unknown. In recent years, mass spectrometry imaging (MSI) has become a booming technology for capturing the spatial accumulation and localization of molecules in fresh plants, animal, or human tissues. However, few studies were conducted on the dried herbal materials due to the obstacles in cryosectioning. In this study, distribution of phytochemicals in the dried root of Isatis tinctoria was revealed by microscopic mass spectrometry imaging, with application of atmospheric pressure-matrix-assisted laser desorption/ionization (AP-MALDI) and ion trap-time-of-flight mass spectrometry (IT-TOF/MS). After optimization of the slice preparation and matrix application, 118 ions were identified without extraction and isolation, and the locations of some metabolites in the dried root of Isatis tinctoria were comprehensively visualized for the first time. Combining with partial least square (PLS) regression, samples collected from four habitats were differentiated unambiguously based on their mass spectrometry imaging.

Hymoins A-D: Two Pairs of Polyprenylated Acylphloroglucinols from Hypericum monogynum and Their Light-Induced Transformation.

Hymoins A-D (1-4), two pairs of light-induced transformative polyprenylated acylphloroglucinols with an unprecedented pentacyclic skeleton, were isolated from the flowers of Hypericum monogynum. The first decarbonylative ring contraction of complex natural products was investigated by light irradiation. Their structures were elucidated by nuclear magnetic resonance analysis, X-ray crystallography, and electronic circular dichroism calculations. In addition, compound 3 showed moderate inhibition efficacy of the platelet-activating-factor-induced aggregation of rabbit platelets.