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1.
Article in English | MEDLINE | ID: mdl-39096004

ABSTRACT

OBJECTIVES: Hereditary transthyretin (TTR) amyloidosis (ATTRv) is frequently complicated by polyneuropathy (ATTRv-PN) and cardiomyopathy (ATTRv-CM). The long-term efficacy of diflunisal on both polyneuropathy and cardiomyopathy in ATTRv patients, especially those with non-V30M genotypes, has not been fully investigated and compared with that of tafamidis. METHODS: We compared the structural and biochemical characteristics of A97S-TTR complexed with tafamidis with those of diflunisal, and prospectively followed up and compared the progression of polyneuropathy and cardiomyopathy between ATTRv-PN patients taking diflunisal and those taking tafamidis. RESULTS: Both diflunisal and tafamidis effectively bind to the two thyroxine-binding sites at the A97S-TTR dimer-dimer interface and equally and almost sufficiently reduce amyloid fibril formation. Thirty-five ATTRv-PN patients receiving diflunisal and 22 patients receiving tafamidis were enrolled. Compared with no treatment, diflunisal treatment significantly delayed the transition of FAP Stage 1 to 2 and Stage 2 to 3 and decreased the deterioration in parameters of the ulnar nerve conduction study (NCS). The progression of FAP stage or NCS parameters did not differ between patients treated with diflunisal and those treated with tafamidis. Both diflunisal and tafamidis treatments significantly decreased radiotracer uptake on 99mTc-PYP SPECT and stabilized cardiac wall thickness and blood pro-B-type natriuretic peptide levels. No significant adverse events occurred during diflunisal or tafamidis treatment. INTERPRETATIONS: The binding patterns of both tafamidis and diflunisal to A97S-TTR closely resembled those observed in the wild type. Diflunisal can effectively delay the progression of polyneuropathy and cardiomyopathy with similar efficacy to tafamidis and may become a cost-effective alternative treatment for late-onset ATTRv-PN.

3.
Environ Monit Assess ; 196(9): 798, 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39115708

ABSTRACT

Watershed ecosystems play a pivotal role in maintaining the global carbon cycle and reducing global warming by serving as vital carbon reservoirs for sustainable ecosystem management. In this study, we based on the "quantity-mechanism-scenario" frameworks, integrate the MCE-CA-Markov and InVEST models to evaluate the spatiotemporal variations of carbon stocks in mid- to high-latitude alpine watersheds in China under historical and future climate scenarios. Additionally, the study employs the Geographic Detector model to explore the driving mechanisms influencing the carbon storage capacity of watershed ecosystems. The results showed that the carbon stock of the watershed increased by about 15.9 Tg from 1980 to 2020. Fractional Vegetation Cover (FVC), Digital Elevation Model (DEM), and Mean Annual Temperature (MAT) had the strongest explanatory power for carbon stocks. Under different climate scenarios, it was found that the SSP2-4.5 scenario had a significant rise in carbon stock from 2020 to 2050, roughly 24.1 Tg. This increase was primarily observed in the southeastern region of the watersheds, with forest and grassland effectively protected. Conversely, according to the SSP5-8.5 scenario, the carbon stock would decrease by about 50.53 Tg with the expansion of cultivated and construction land in the watershed's southwest part. Therefore, given the vulnerability of mid- to high-latitude mountain watersheds, global warming trends continue to pose a greater threat to carbon sequestration in watersheds. Our findings carry important implications for tackling potential ecological threats in mid- to high-latitude watersheds in the Northern Hemisphere and assisting policymakers in creating carbon sequestration plans, as well as for reducing climate change.


Subject(s)
Carbon , Climate Change , Ecosystem , Environmental Monitoring , China , Carbon/analysis , Carbon Sequestration , Carbon Cycle , Conservation of Natural Resources , Models, Theoretical
4.
Eur J Radiol ; 178: 111647, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39068857

ABSTRACT

PURPOSE: Intraplaque haemorrhage (IPH) is a well-known risk factor for faster plaque progression (volume increase); however, its etiology is unclear. We aimed at determining what other local plaque- and systemic factors contribute to plaque progression and to the development and progression of IPH. METHODS: We examined 98 asymptomatic participants with carotid plaque using serial multi-contrast magnetic resonance imaging. We measured the percent of wall volume (%WV=100 x [wall volume] / [total vessel volume]) and measured IPH and calcification volumes. We used generalized estimating equations-based regression to analyze predictors of %WV change and new IPH while accounting for covariates (sex, age and statin use), and multiple non-independent observations per participant. RESULTS: Total follow-up was 1.8 ± 0.8 years on average. The presence of IPH (ß: 0.6 %/y, p = 0.033) and calcification (ß: 1.2 %/y, p = 0.028) were each associated with faster plaque progression. New IPH, detected on a subsequent scan in 4 % of arteries that did not initially have IPH, was associated with larger calcification (odds ratio [OR]: 2.6 per 1-SD increase, p = 0.038) and higher pulse pressure (OR: 2.3 per 1-SD increase, p = 0.016). Larger calcification was associated with greater increases in pulse pressure (ß: 1.4 mm Hg/y per 1-SD increase, p = 0.040). CONCLUSIONS: IPH and calcification are each independently associated with faster plaque progression. The association of carotid calcification to increased pulse pressure and new IPH development suggests a possible mechanism by which calcification drives IPH development and plaque progression.

5.
Phytochemistry ; 224: 114149, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38763314

ABSTRACT

Farnesylated chalcones were favored by researchers due to their different biological activities. However, only five naturally occurring farnesylated chalcones were described in the literature until now. Here, the farnesylation of six chalcones by the Aspergillus terreus aromatic prenyltransferase AtaPT was reported. Fourteen monofarnesylated chalcones (1F1-1F5, 2F1-2F3, 3F1, 3F2, 4F1, 4F2, 5F1, 6F1, and 6F2) and a difarnesylated product (2F3) were obtained, enriching the diversity of natural farnesylated chalcones significantly. Ten of them are C-farnesylated products, which complement O-farnesylated chalcones by chemical synthesis. Fourteen products have not been reported prior to this study. Nine of the produced compounds (1F2-1F5, 2F1-2F3, 5F1, and 6F1) exhibited inhibitory effect on α-glucosidase with IC50 values ranging from 24.08 ± 1.44 to 190.0 ± 0.28 µM. Among them, compounds 2F3 with IC50 value at 24.08 ± 1.44 µM and 1F4 with IC50 value at 30.09 ± 0.59 µM showed about 20 times stronger than the positive control acarbose with an IC50 at 536.87 ± 24.25 µM in α-glucosidase inhibitory assays.


Subject(s)
Aspergillus , Chalcones , Dimethylallyltranstransferase , Dimethylallyltranstransferase/metabolism , Dimethylallyltranstransferase/chemistry , Dimethylallyltranstransferase/antagonists & inhibitors , Chalcones/chemistry , Chalcones/pharmacology , Chalcones/metabolism , Aspergillus/enzymology , Aspergillus/chemistry , Molecular Structure , Prenylation , Structure-Activity Relationship , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , alpha-Glucosidases/metabolism , alpha-Glucosidases/chemistry , Dose-Response Relationship, Drug
6.
J Am Coll Cardiol ; 83(21): 2112-2127, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38777513

ABSTRACT

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide and challenges the capacity of health care systems globally. Atherosclerosis is the underlying pathophysiological entity in two-thirds of patients with CVD. When considering that atherosclerosis develops over decades, there is potentially great opportunity for prevention of associated events such as myocardial infarction and stroke. Subclinical atherosclerosis has been identified in its early stages in young individuals; however, there is no consensus on how to prevent progression to symptomatic disease. Given the growing burden of CVD, a paradigm shift is required-moving from late management of atherosclerotic CVD to earlier detection during the subclinical phase with the goal of potential cure or prevention of events. Studies must focus on how precision medicine using imaging and circulating biomarkers may identify atherosclerosis earlier and determine whether such a paradigm shift would lead to overall cost savings for global health.


Subject(s)
Atherosclerosis , Early Diagnosis , Precision Medicine , Humans , Atherosclerosis/diagnosis , Precision Medicine/methods , Biomarkers/blood
7.
EClinicalMedicine ; 72: 102622, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38745965

ABSTRACT

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

8.
Cancers (Basel) ; 16(10)2024 May 07.
Article in English | MEDLINE | ID: mdl-38791869

ABSTRACT

This study uses Monte Carlo simulation and experimental measurements to develop a predictive model for estimating the external dose rate associated with permanent radioactive source implantation in prostate cancer patients. The objective is to estimate the accuracy of the patient's external dose rate measurement. First, I-125 radioactive sources were implanted into Mylar window water phantoms to simulate the permanent implantation of these sources in patients. Water phantom experimental measurement was combined with Monte Carlo simulation to develop predictive equations, whose performance was verified against external clinical data. The model's accuracy in predicting the external dose rate in patients with permanently implanted I-125 radioactive sources was high (R2 = 0.999). A comparative analysis of the experimental measurements and the Monte Carlo simulations revealed that the maximum discrepancy between the measured and calculated values for the water phantom was less than 5.00%. The model is practical for radiation safety assessments, enabling the evaluation of radiation exposure risks to individuals around patients with permanently implanted I-125 radioactive sources.

9.
Article in English | MEDLINE | ID: mdl-38789121

ABSTRACT

BACKGROUND AND PURPOSE: The Circle of Willis (COW) is a crucial mechanism for cerebral collateral circulation. This proof-ofconcept study aims to develop and assess an analysis method to characterize the hemodynamics of the arterial segments in COW using arterial spin labeling (ASL) based non-contrast enhanced dynamic magnetic resonance angiography (dMRA). MATERIALS AND METHODS: The developed analysis method uses a graph model, bootstrap strategy, and ensemble learning methodologies to determine the time-curve shift from ASL dMRA to estimate the flow direction within the COW. The performance of the method was assessed on 52 subjects, using the flow direction, either antegrade or retrograde, derived from 3D phase contrast (PC) MRI as the reference. RESULTS: A total of 340 arterial segments in COW were evaluated, among which 30 (8.8%) had retrograde flow according to 3D PC. The ASL dMRA-based flow direction estimation has an accuracy, sensitivity, and specificity of 95.47%, 80%, and 96.34%, respectively. CONCLUSIONS: Using ASL dMRA and the developed image analysis method to estimate the flow direction in COW is feasible. This study provides a new method to assess the hemodynamics of the COW, which could be useful for the diagnosis and study of cerebrovascular diseases. ABBREVIATIONS: COW = Circle of Willis; ASL = arterial spin labeling; dMRA =dynamic magnetic resonance angiography; PC = phase contrast.

11.
Nat Commun ; 15(1): 4554, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38811587

ABSTRACT

High-entropy alloys (HEAs) provide new research avenues for alloy combinations in the periodic table, opening numerous possibilities in novel-alloy applications. However, their electrical characteristics have been relatively underexplored. The challenge in establishing an HEA electrical conductivity model lies in the changes in electronic characteristics caused by lattice distortion and complexity of nanostructures. Here we show a low-frequency electrical conductivity model for the Nb-Mo-Ta-W HEA system. The cocktail effect is found to explain trends in electrical-conductivity changes in HEAs, while the magnitude of the reduction is understood by the calculated plasma frequency, free electron density, and measured relaxation time by terahertz spectroscopy. As a result, the refractory HEA Nb15Mo35Ta15W35 thin film exhibits both high hardness and excellent conductivity. This combination of Nb15Mo35Ta15W35 makes it suitable for applications in atomic force microscopy probe coating, significantly improving their wear resistance and atomic-scale image resolution.

12.
J Agric Food Chem ; 72(14): 8018-8026, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38557039

ABSTRACT

Phloretin is widely found in fruit and shows various biological activities. Here, we demonstrate the dimethylallylation, geranylation, and farnesylation, particularly the first dimethylallylation at the nonaromatic carbon of phloretin (1) by the fungal prenyltransferase AnaPT and its mutants. F265 was identified as a key amino acid residue related to dimethylallylation at the nonaromatic carbon of phloretin. Mutants AnaPT_F265D, AnaPT_F265G, AnaPT_F265P, AnaPT_F265C, and AnaPT_F265Y were discovered to generally increase prenylation activity toward 1. AnaPT_F265G catalyzes the O-geranylation selectively at the C-2' hydroxyl group, which involves an intramolecular hydrogen bond with the carbonyl group of 1. Seven products, 1D5, 1D7-1D9, 1G2, 1G4, and 1F2, have not been reported prior to this study. Twelve compounds, 1D3-1D9, 1G1-1G3, and 1F1-1F2, exhibited potential inhibitory effects on α-glucosidase with IC50 values ranging from 11.45 ± 0.87 to 193.80 ± 6.52 µg/mL. Among them, 1G1 with an IC50 value of 11.45 ± 0.87 µg/mL was the most potential α-glucosidase inhibitor, which is about 30 times stronger than the positive control acarbose with an IC50 value of 346.63 ± 15.65 µg/mL.


Subject(s)
Dimethylallyltranstransferase , Phloretin , Phloretin/pharmacology , Indoles/chemistry , Carbon , Catalysis , Prenylation
13.
J Agric Food Chem ; 72(14): 8225-8236, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38557068

ABSTRACT

As a continuous flow investigation of novel pesticides from natural quinolizidine alkaloids, the chemical compositions of the seeds of Sophora alopecuroides were thoroughly researched. Fifteen new aloperine-type alkaloids (1-15) as well as six known aloperine-type alkaloids (16-21) were obtained from the extract of S. alopecuroides. The structures of 1-21 were confirmed via HRESIMS, NMR, UV, IR, ECD calculations, and X-ray diffraction. The antiviral activities of 1-21 against tobacco mosaic virus (TMV) were detected following the improved method of half-leaf. Compared with ningnanmycin (protective: 69.7% and curative: 64.3%), 15 exhibited excellent protective (71.7%) and curative (64.6%) activities against TMV. Further biological studies illustrated that 15 significantly inhibited the transcription of the TMV-CP gene and increased the activities of polyphenol oxidase (PPO), peroxidase (POD), superoxide dismutase (SOD), and phenylalanine ammonia-lyase (PAL). The antifungal activities of 1-21 against Phytophythora capsica, Botrytis cinerea, Alternaria alternata, and Gibberella zeae were screened according to a mycelial inhibition test. Compound 13 displayed excellent antifungal activity against B. cinerea (EC50: 7.38 µg/mL). Moreover, in vitro antifungal mechanism studies displayed that 13 causes accumulation of reactive oxygen species and finally leads to mycelia cell membrane damage and cell death in vitro.


Subject(s)
Alkaloids , Quinolizidines , Sophora , Tobacco Mosaic Virus , Antifungal Agents , Sophora/chemistry , Alkaloids/chemistry , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Seeds/chemistry
14.
Opt Express ; 32(7): 12982-12991, 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38571104

ABSTRACT

Quantum dense metrology (QDM) performs high-precision measurements by a two-mode entangled state created by an optical parametric amplifier (PA), where one mode is a meter beam and the other is a reference beam. In practical applications, the photon losses of meter beam are unavoidable, resulting in a degradation of the sensitivity. Here, we employ coherent feedback that feeds the reference beam back into the PA by a beam splitter to enhance the sensitivity in a lossy environment. The results show that the sensitivity is enhanced significantly by adjusting the splitting ratio of the beam splitter. This method may find its potential applications in QDM. Furthermore, such a strategy that two non-commuting observables are simultaneous measurements could provide a new way to individually control the noise-induced random drift in phase or amplitude of the light field, which would be significant for stabilizing the system and long-term precision measurement.

15.
medRxiv ; 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38496424

ABSTRACT

Background: Nineteen genomic regions have been associated with high-grade serous ovarian cancer (HGSOC). We used data from the Ovarian Cancer Association Consortium (OCAC), Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA), UK Biobank (UKBB), and FinnGen to identify novel HGSOC susceptibility loci and develop polygenic scores (PGS). Methods: We analyzed >22 million variants for 398,238 women. Associations were assessed separately by consortium and meta-analysed. OCAC and CIMBA data were used to develop PGS which were trained on FinnGen data and validated in UKBB and BioBank Japan. Results: Eight novel variants were associated with HGSOC risk. An interesting discovery biologically was finding that TP53 3'-UTR SNP rs78378222 was associated with HGSOC (per T allele relative risk (RR)=1.44, 95%CI:1.28-1.62, P=1.76×10-9). The optimal PGS included 64,518 variants and was associated with an odds ratio of 1.46 (95%CI:1.37-1.54) per standard deviation in the UKBB validation (AUROC curve=0.61, 95%CI:0.59-0.62). Conclusions: This study represents the largest GWAS for HGSOC to date. The results highlight that improvements in imputation reference panels and increased sample sizes can identify HGSOC associated variants that previously went undetected, resulting in improved PGS. The use of updated PGS in cancer risk prediction algorithms will then improve personalized risk prediction for HGSOC.

16.
Zhen Ci Yan Jiu ; 49(3): 283-288, 2024 Mar 25.
Article in English, Chinese | MEDLINE | ID: mdl-38500325

ABSTRACT

OBJECTIVES: To observe the therapeutic effect of transcutaneous electrical acupoint stimulation (TEAS) based on the theory of "qi ascending and descending movement" in patients after general anesthesia laparoscopic cholecystectomy, so as to explore the impact of TEAS on the autonomic nervous system and gastrointestinal function of patients. METHODS: A total of 204 patients scheduled to undergo general anesthesia laparoscopic cholecystectomy were selected and randomly divided into control, double acupoints and multiple acupoints groups, with 68 cases in each group. For patients in the multiple acupoints group, TEAS was applied at Zusanli (ST36), Tiantu (CV22), Danzhong (CV17), Zhongwan (CV12), Taichong (LR3), and Neiguan (PC6) 30 min before anesthesia induction until the end of the surgery. In the double acupoints group, TEAS was applied only at ST36 and PC6. No electrical stimulation was applied in the control group. The postoperative bloating, bowel sound recovery time, first farting time, first defecation time, length of hospital stay, nausea and vomiting were compared among the three groups. Heart rate variability was monitored by twelve-lead electrocardiogram to evaluate the autonomic nervous function of the patients, including the low frequency power/high frequency power ratio (LF/HF), the standard deviation of all sinus RR intervals (SDNN), and the root mean square of difference between successive normal RR intervals (RMSSD). RESULTS: At 6 h and 24 h after surgery, the symptoms of bloating, nausea and vomiting in the multiple acupoints group and double acupoints group were significantly improved compared to the control group (P<0.05), and the multiple acupoints group was superior to the double acupoints group (P<0.05). Compared with the control group, the bowel sound recovery time, first farting time, first defecation time, and length of hospital stay were significantly shorter (P<0.05) in the multiple acupoints group and double acupoints group, and the multiple acupoints group was superior to the double acupoints group (P<0.05). At 1 d and 2 d after surgery, compared with the control group, LF/HF was decreased (P<0.05) while SDNN and RMSSD were increased (P<0.05) in the multiple acupoints group and double acupoints group, and there was a significant difference between the two groups (P<0.05). CONCLUSIONS: TEAS treatment based on the theory of "qi ascending and descending movement" can relieve gastrointestinal dysfunction, reduce early postoperative sympathetic nerve excitement and maintain parasympathetic nerve tension in patients after general anesthesia laparoscopic cholecystectomy, thereby promoting gastrointestinal function recovery.


Subject(s)
Cholecystectomy, Laparoscopic , Transcutaneous Electric Nerve Stimulation , Humans , Cholecystectomy, Laparoscopic/adverse effects , Acupuncture Points , Qi , Autonomic Nervous System , Nausea , Vomiting , Anesthesia, General
17.
Nanoscale ; 16(15): 7660-7669, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38529700

ABSTRACT

The development of layered metal sulfides with stable structure and accessible active sites is of great importance for sodium-ion batteries (SIBs). Herein, a simple liquid-mixing method is elaborately designed to immobilize WS2 nanoflakes on N-doped carbon (NC), then further coat carbon to produce WS2/NC@C. In the formation process of this composite, the presence of NC not only avoids the overlap and improves the dispersion of WS2 nanoflakes, but also creates a connection network for charge transfer, where the wrapped carbon provides a stable chemical and electrochemical reaction interface. Thus, the composite of WS2/NC@C exhibits the desired Na+ storage capacity as anticipated. The reversible capacity reaches the high value of 369.8 mA h g-1 at 0.2 A g-1 after 200 cycles, while excellent rate performances and cycle life are also acquired in that capacity values of 256.7 and 219.6 mA h g-1 at 1 and 5 A g-1 are preserved after 1000 cycles, respectively. In addition, the assembled sodium-ion hybrid capacitors (SIHCs, AC//WS2/NC@C) exhibit an energy/power density of 68 W h kg-1 at 64 W kg-1, and capacity retention of 82.9% at 1 A g-1 after 2000 cycles. The study provides insight into developing layered metal sulfides with eminent performance of Na+ storage.

18.
J Agric Food Chem ; 72(12): 6711-6722, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38491973

ABSTRACT

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.


Subject(s)
Fungicides, Industrial , Magnoliopsida , Humans , HEK293 Cells , Fungicides, Industrial/chemistry , Antifungal Agents/pharmacology , Nicotiana , Coumarins/chemistry , Structure-Activity Relationship
19.
J Agric Food Chem ; 72(9): 5047-5061, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38394631

ABSTRACT

As part of our ongoing investigation of natural bioactive substances from the genus Thermopsis of the tribe Fabaceae for agricultural protection, the chemical constituents of the herb Thermopsis lupinoides were systematically investigated, which led to the isolation of 39 quinolizidine alkaloids (QAs) (1-39), including 14 new QAs (1-14) and 14 isoflavones (40-53). Their structures were elucidated through comprehensive spectroscopic data analysis (IR, UV, NMR, HRESIMS), ECD calculations, and X-ray crystallography. The antitomato spotted wilt virus (TSWV) and antifungal (against Botrytis cinerea, Gibberella zeae, Phytophythora capsica, and Alternaria alternata) and insecticidal (against Aphis fabae and Tetranychus urticae) activities of the isolated compounds were screened using the lesion counting method, mycelial inhibition assay, and spray method, respectively. The bioassay results showed that 34 exhibited excellent protective activity against TSWV, with an EC50 value of 36.04 µg/mL, which was better than that of the positive control, ningnanmycin (86.03 µg/mL). The preliminary mechanistic exploration illustrated that 34 induced systemic acquired resistance in the host plant by acting on the salicylic acid signaling pathway. Moreover, 1 showed significant antifungal activity against B. cinerea (EC50 value of 20.83 µg/mL), while 2 exhibited good insecticidal activity against A. fabae (LC50 value of 24.97 µg/mL). This research is promising for the invention of novel pesticides from QAs with high efficiency and satisfactory ecological compatibility.


Subject(s)
Fabaceae , Fungicides, Industrial , Insecticides , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Fungicides, Industrial/pharmacology , Fungicides, Industrial/chemistry , Quinolizidine Alkaloids , Insecticides/pharmacology , Insecticides/chemistry , Antiviral Agents/pharmacology , Structure-Activity Relationship
20.
Article in English | MEDLINE | ID: mdl-38306261

ABSTRACT

Reconstructing a spline surface from a given arbitrary topological triangle mesh is a fundamental and challenging problem in computer-aided design and engineering. This paper introduces a novel surface fitting method utilizing G-NURBS capable of handling control meshes with arbitrary topologies. This method employs adaptive control point adjustment, guided by the geometric attributes of the input model, ensuring precise representation of sharp features such as edges and corners. Two primary strategies are employed: a parameter correspondence approach designed for sharp features and a control mesh iterative refinement technique that incorporates geometrical feature information. The proposed method has been tested and evaluated on various CAD models to demonstrate its effectiveness. This method can achieve higher fitting accuracy while faithfully preserving the geometrical features with fewer control points.

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