A review on triterpenoid and triterpenoid saponins from Xanthoceras sorbifolium Bung.

Xanthoceras sorbifolium Bunge, also known as Tu-Mu-Gua and Wen-Dan-Ge-Zi, has several applications. Clinical data and experimental studies have shown anti-tumor, anti-inflammatory, anti-bacterial, and anti-oxidant properties of Xanthoceras sorbifolium Bunge that inhibits prostate hyperplasia, lowers blood pressure and lipid level, and treats enuresis and urinary incontinence. It also has neuroprotective effects and can treat Alzheimer's disease and Parkinson's syndrome. The research on the chemical composition and pharmacological effects of Xanthoceras sorbifolium Bunge has been increasing. Triterpenoid and triterpenoid saponins are the main constituents in Xanthoceras sorbifolium Bunge and exhibit biological activities. In this review, we summarized the research progress on triterpenoids and their glycosides in Xanthoceras sorbifolia, including the chemical constituents, pharmacological activities, and biogenic pathways of triterpenoid mother nucleus. The results would provide a reference for further research and development of triterpenoids and their glycosides in Xanthoceras sorbifolia.

Gene doping detection in the era of genomics.

Recent progress in gene editing has enabled development of gene therapies for many genetic diseases, but also made gene doping an emerging risk in sports and competitions. By delivery of exogenous transgenes into human body, gene doping not only challenges competition fairness but also places health risk on athletes. World Anti-Doping Agency (WADA) has clearly inhibited the use of gene and cell doping in sports, and many techniques have been developed for gene doping detection. In this review, we will summarize the main tools for gene doping detection at present, highlight the main challenges for current tools, and elaborate future utilizations of high-throughput sequencing for unbiased, sensitive, economic and large-scale gene doping detections. Quantitative real-time PCR assays are the widely used detection methods at present, which are useful for detection of known targets but are vulnerable to codon optimization at exon-exon junction sites of the transgenes. High-throughput sequencing has become a powerful tool for various applications in life and health research, and the era of genomics has made it possible for sensitive and large-scale gene doping detections. Non-biased genomic profiling could efficiently detect new doping targets, and low-input genomics amplification and long-read third-generation sequencing also have application potentials for more efficient and straightforward gene doping detection. By closely monitoring scientific advancements in gene editing and sport genetics, high-throughput sequencing could play a more and more important role in gene detection and hopefully contribute to doping-free sports in the future.

Tradeoff analysis between time cost and energy cost for fixed-time synchronization of discontinuous neural networks.

This article focuses on the tradeoff analysis between time and energy costs for fixed-time synchronization (FXTS) of discontinuous neural networks (DNNs) with time-varying delays and mismatched parameters. First, a more comprehensive lemma is systematically established to study fixed-time stability, which is less conservative than those in most current results. Besides, theoretical proof has proven that the upper bounds of the settling time (ST) in this article are more accurate compared to existing results. Second, on the grounds of the new fixed-time stability lemma, fixed-time synchronization problem for discontinuous neural networks with time-varying delays and mismatched parameters is explored, and sufficient conditions for fixed-time synchronization are obtained. Further, the upper bounds of energy cost during the synchronization process are estimated. Third, in order to achieve a balance between time cost and energy cost, the genetic algorithm is utilized to find the satisfactory control parameter. Finally, a numerical example is provided to verify the theoretical analysis's correctness and the control mechanism's feasibility.

Radiomics from dual-energy CT-derived iodine maps predict lymph node metastasis in head and neck squamous cell carcinoma.

OBJECTIVE: To develop and validate an iodine maps-based radiomics nomogram for preoperatively predicting cervical lymph node metastasis (LNM) in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: A total of 278 patients who pathologically confirmed as HNSCC were retrospectively recruited from two medical centers between June 2012 and July 2022. The training set (n = 152) and internal set (n = 67) were randomly selected from medical center A, and the patients from medical center B were enrolled as the external set (n = 69). The minority group in the training set was balanced by the adaptive synthetic sampling (ADASYN) approach. Radiomics features were extracted from dual-energy CT-derived iodine maps at arterial phase (AP) and venous phase (VP), respectively. Three radiomics signatures were constructed to predict the LNM by using a random forest algorithm. The independent clinical predictors for LNM were identified by multivariate analysis and combined with radiomics signatures to establish a radiomic-clinical nomogram. The performance of radiomic-clinical nomogram was evaluated with respect to its discrimination and clinical usefulness. RESULTS: The AP-VP-incorporated radiomics model exhibited a great predictive performance for LNM prediction with an area under curve (AUC) of 0.885 (95% CI, 0.836-0.933) in ADASYN-training set and confirmed in all validation sets. The nomogram that incorporated AP-VP radiomics signatures, CT-reported LN status, and histological grades yielded AUCs of 0.920 (95% CI, 0.881-0.959) in ADASYN-training set, 0.858 (95% CI, 0.771-0.944) in internal validation, and 0.849 (95% CI, 0.752-0.946) in external validation, with good calibration in all cohorts (p > 0.05). Decision curve analyses indicated the nomogram was clinically useful. In addition, the predictive performance of clinical-radiomics nomogram was also validation in combing cohorts. Stratified analysis confirmed the stability of nomogram, particularly in group negative for CT-reported LNM. CONCLUSION: Clinical-radiomics nomogram based on iodine maps exhibited promising performance in predicting LNM and providing valuable information for making individualized therapy decisions.

Heavy metal contamination in Shanghai agricultural soil.

As heavy metals in soil could enrich in biomass and pose health risk to human, it is vital to monitor their contaminations to ensure qualified agricultural production. In this study, we collected >4000 soil samples from agricultural fields in Shanghai during 2010∼2020, and unveiled heavy metal contamination status in this metropolitan. We found that although Shanghai has a long industrialization history, the heavy metal levels in agricultural soil are within safe ranges according to national standard. Specifically, the median levels of Cd, Hg, As, Pb, Cr and Cu are 0.11, 0.13, 7.47, 23.80, 41.00 and 28.30 mg/kg, respectively, which are as good as, or even better than national averages. However, there are spatial and temporal heterogeneities for heavy metal contaminations in Shanghai. For example, the levels of Cd, Hg and Cr are relatively higher in some districts with high industry density, which should be further monitored in the future. Moreover, while the levels for Cd, Cr and Pb have decreased, the level for Hg has mildly increased during this period which needs counteractive measures. Correlation analysis of heavy metal levels and soil fertility parameters suggested overuse of fertilizers may be related to heavy metal contamination in some regions. In summary, our study present by far the largest and most comprehensive landscape of heavy metal contamination in Shanghai agricultural soil, which will be useful for future policy-design and land use planning to ensure safe agricultural production.

Effective TME-related signature to predict prognosis of patients with head and neck squamous cell carcinoma.

Introduction: The tumor microenvironment (TME) is crucial for the development of head and neck squamous cell carcinoma (HNSCC). However, the correlation of the characteristics of the TME and the prognosis of patients with HNSCC remains less known. Methods: In this study, we calculated the immune and stromal cell scores using the "estimate" R package. Kaplan-Meier survival and CIBERSORT algorithm analyses were applied in this study. Results: We identified seven new markers: FCGR3B, IGHV3-64, AC023449.2, IGKV1D-8, FCGR2A, WDFY4, and HBQ1. Subsequently, a risk model was constructed and all HNSCC samples were grouped into low- and high-risk groups. The results of both the Kaplan-Meier survival and receiver operating characteristic curve (ROC) analyses showed that the prognosis indicated by the model was accurate (0.758, 0.756, and 0.666 for 1-, 3- and 5-year survival rates). In addition, we applied the CIBERSORT algorithm to reveal the significant differences in the infiltration levels of immune cells between the two risk groups. Discussion: Our study elucidated the roles of the TME and identified new prognostic biomarkers for patients with HNSCC.

Epicardial fat in patients with metabolic syndrome: A systematic review and meta-analysis.

PURPOSE: Abnormally increased epicardial fat appears to be associated with an additional risk of major adverse cardiovascular events (MACEs) in the context of metabolic syndrome (MetS). However, evidence on the relationship between epicardial fat volumes (EFVs), epicardial fat thickness (EFT) and MetS remains inconsistent. METHODS: Specific searches of electronic databases from 1 January 2000 to 31 October 2022 were independently performed by two researchers. In this study, two quantification measures of epicardial fat were included: comparison of total computed tomography-based EFVs and EFT between two groups (individuals with and without MetS), estimating standardized mean difference (SMD) with corresponding 95 % confidence intervals (CIs) through a random-effects model analysis. The heterogeneity in the included studies was explored by meta-regression and subgroup analyses. RESULTS: The EFVs were significantly increased in MetS subjects compared with non-MetS subjects (SMD: 1.07, 95 % CI: 0.69-1.45, p < 0.001), and the EFT was also significantly larger in MetS patients than in the Non-MetS (SMD: 1.12, 95 % CI: 0.84-1.41, p < 0.001). We compared the Caucasian and American subgroups with the Asian and African subgroups, and the EFT was greater in the former subgroups (SMD: 1.32, 95 % CI: 0.44-2.20, p < 0.001). When comparing the EFT among the age subgroups, there was a significant SMD between adolescents and adults or elderly individuals (SMD: 1.21, 95 % CI: 0.84-1.52, p < 0.001). CONCLUSIONS: MetS patients tend to present greater EFT near the right ventricular free wall and greater total EFVs. Increased epicardial fat, an imaging biomarker, independently affects the onset of MetS.

The impact of industrial land mismatch on carbon emissions in resource-based cities under environmental regulatory constraints-evidence from China.

Achieving carbon neutrality has become a global common goal. For China, to reach peak carbon emissions and long-term carbon neutrality, the transformation and development of resource-based cities are essential. This study uses data from 114 prefecture-level resource-based cities from 2008 to 2019 as a sample and empirically tests the impact of industrial land mismatch on carbon emissions using the fixed effects model. In addition, we analyze the heterogeneous influence of environmental regulation as a moderating effect on resource-based cities at different development stages. The study reveals that (1) there is a significant positive correlation between the imbalance in industrial land supply in resource-based cities and carbon emissions. The more severe the imbalance, the higher the carbon emissions. The improper supply mode of industrial land is also positively correlated with carbon emissions, although the impact is not significant. (2) Environmental regulation can significantly curb the carbon emission issues caused by the mismatch and imbalance in the scale of industrial land supply and the improper supply mode of industrial land. (3) Compared to strong resource-based cities, weak resource-security cities have a smaller impact on carbon emissions due to an imbalance in the supply of industrial land. This is mainly because resources in weak resource-security cities are becoming exhausted, making "ecology first, green and low carbon" the main tune for economic and social development. Both types of cities show a positive correlation between the improper supply of industrial land and carbon emissions, although neither is significant. (4) The intensity of the regulatory effect of environmental regulations on resource-based cities is influenced by resource abundance. The suppression of carbon emissions by environmental regulations is more apparent in strong resource-security cities than in weak resource-security cities.

Skeleton Synthesis of a Plant-Derived Radioprotective Alkaloid Born to Produce a Novel Fused Heterocycle.

Alkaloids are a material treasure bestowed on humans by nature owing to their numerous biological activities. Orychophragine D, an alkaloid isolated from the seeds of Orychophragmus violaceus was identified as bearing a novel skeleton and proved to have an excellent radioprotective effect. Different from the common alkaloid structure, the main block of orychophragine D is constructed of an oxotriazine and an oxopiperazine, which are connected in parallel by a C-N bond. In this paper, a preparation method for the novel heterocycle skeleton of orychophragine D is proposed for the first time. N-Boc-L-serine was utilized as the original material to complete the preparation with 11 steps in a 13% overall yield. A hydroxyl group was established on the side chain of the skeleton as the reaction site for researchers to conduct further structural modification or derivatization.

The role of altered lipid composition and distribution in liver fibrosis revealed by multimodal nonlinear optical microscopy.

Intracellular lipid accumulation is commonly seen in fibrotic livers, but its exact role in liver fibrosis remains elusive. Here, we established a multimodal nonlinear optical microscopy to quantitatively map distribution of biomolecules in fibrotic livers. Our data revealed that unsaturated triglycerides were predominantly accumulated in central vein area during liver fibrosis but not in portal vein area. Moreover, the lipid homeostasis was remarkably dysregulated in the late-stage compared to the early-stage fibrosis, including increased unsaturated triglycerides with decreased lipid unsaturation degree and decreased membrane fluidity. Such alterations were likely due to up-regulated lipogenesis, desaturation, and peroxidation, which consequently led to endoplasmic reticulum stress and cell death. Inspiringly, injured hepatocyte could be rescued by remodeling lipid homeostasis via either supply of unsaturated fatty acids or enhancement of membrane fluidity. Collectively, our study improves current understanding of the role of lipid homeostasis in fibrosis and open opportunities for treatment.

Bio-inspired magnetic-driven folded diaphragm for biomimetic robot.

Functional soft materials, exhibiting multiple types of deformation, have shown their potential/abilities to achieve complicated biomimetic behaviors (soft robots). Inspired by the locomotion of earthworm, which is conducted through the contraction and stretching between body segments, this study proposes a type of one-piece-mold folded diaphragm, consisting of the structure of body segments with radial magnetization property, to achieve large 3D and bi-directional deformation with inside-volume change capability subjected to the low homogeneous magnetically driving field (40 mT). Moreover, the appearance based on the proposed magnetic-driven folded diaphragm is able to be easily customized to desired ones and then implanted into different untethered soft robotic systems as soft drivers. To verify the above points, we design the diaphragm pump providing unique properties of lightweight, powerful output and rapid response, and the soft robot including the bio-earthworm crawling robot and swimming robot inspired by squid to exhibit the flexible and rapid locomotion excited by single homogeneous magnetic fields.

Purification of total flavonoids from Ginkgo biloba flowers with resin column chromatography and evaluation of antioxidant activities in vitro.

Purification of total flavonoids from Ginkgo biloba flowers (GBF) extracts were studied using six resins. Adsorption-desorption experiments indicated that polyamide resin is the most suitable resin. The optimal purification process of total flavonoids of GBF was as follows: a loading concentration of 5.85 mg/mL, a loading volume of 1 bed volume (BV), a loading flow rate of 2 BV/h, a water volume of 2.67 BV, and a desorption solution of 40% ethanol. Under these conditions, the maximum purity of total flavonoids was 37.1 ± 1.1%. The antioxidant activity of purified flavonoids was further evaluated in vitro. It showed that the 40% ethanol purified fraction (Fr. B) group had the strongest antioxidant activity of the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity concentration for 50% of maximal effect (EC50, 145.4 ± 13.8 µg/mL) and ferric reducing ability (2.5 ± 0.2 mM FeSO4 equivalent mg-1 Fr. B). In addition, at the concentration of 160 µg/mL, the Fr. B strikingly increased the viability rate of hydrogen peroxide stimulated PC-12 cells to normal levels (***p < 0.001). This method provides a basis for the application and development of GBF resources. It indicated that the purified GBF flavonoids can be used as a source of potential antioxidant.

Correlation analysis between extrusion process variables and quality of purslane leaf powder rice extrudates.

Extrusion has become one of the most popular techniques in food processing, and the process parameters are closely related to product quality. Purslane (Portulaca oleracea L.) can be used in medical and food products as a vegetable and herb. It has limited application in extrusion. The effects of extrusion process variables (screw speed, barrel temperature, and feed moisture) on system variables (specific mechanical energy [SME], die head pressure, and torque) and target variables (water absorption index, water solubility index, iodine blue value, color, pasting properties, and textural properties) of purslane powder compound rice were studied. The results showed that SME was moderately positively correlated with screw speed (r = 0.608, p < 0.05). However, torque was moderately negatively correlated with feed moisture (r = -0.574, p < 0.05), and die head pressure was moderately negatively correlated with barrel temperature (r = -0.635, p < 0.01). The target variables of extrudates were also correlated with the system parameters to varying degrees. These results are helpful to control and predict the texture, pasting properties, and other quality characteristics of extruded products containing purslane powder. PRACTICAL APPLICATION: The results showed that torque and die head pressure were moderately negatively related to barrel temperature, specific mechanical energy was moderately positively related to screw speed, peak viscosity and breakdown viscosity were moderately negatively related to specific mechanical energy, and water absorption index was moderately negatively related to torque and die head pressure. It provides a reference for the research of influencing system parameters and changing product quality by controlling extrusion process parameters. In this study, some possibilities for the application of broken rice and purslane in extrusion processing were proposed.

High-content imaging of human hepatic spheroids for researching the mechanism of duloxetine-induced hepatotoxicity.

Duloxetine (DLX) has been approved for the successful treatment of psychiatric diseases, including major depressive disorder, diabetic neuropathy, fibromyalgia and generalized anxiety disorder. However, since the usage of DLX carries a manufacturer warning of hepatotoxicity given its implication in numerous cases of drug-induced liver injuries (DILI), it is not recommended for patients with chronic liver diseases. In our previous study, we developed an enhanced human-simulated hepatic spheroid (EHS) imaging model system for performing drug hepatotoxicity evaluation using the human hepatoma cell line HepaRG and the support of a pulverized liver biomatrix scaffold, which demonstrated much improved hepatic-specific functions. In the current study, we were able to use this robust model to demonstrate that the DLX-DILI is a human CYP450 specific, metabolism-dependent, oxidative stress triggered complex hepatic injury. High-content imaging analysis (HCA) of organoids exposed to DLX showed that the potential toxicophore, naphthyl ring in DLX initiated oxidative stress which ultimately led to mitochondrial dysfunction in the hepatic organoids, and vice versa. Furthermore, DLX-induced hepatic steatosis and cholestasis was also detected in the exposed EHSs. We also discovered that a novel compound S-071031B, which replaced DLX's naphthyl ring with benzodioxole, showed dramatically lower hepatotoxicities through reducing oxidative stress. Thus, we conclusively present the human-relevant EHS model as an ideal, highly competent system for evaluating DLX induced hepatotoxicity and exploring related mechanisms in vitro. Moreover, HCA use on functional hepatic organoids has promising application prospects for guiding compound structural modifications and optimization in order to improve drug development by reducing hepatotoxicity.

Hepatic Organoid-Based High-Content Imaging Boosts Evaluation of Stereoisomerism-Dependent Hepatotoxicity of Stilbenes in Herbal Medicines.

The complexity of chemical components of herbal medicines often causes great barriers to toxicity research. In our previous study, we have found the critical divergent hepatotoxic potential of a pair of stilbene isomers in a famous traditional Chinese herb, Polygonum multiflorum (Heshouwu in Chinese). However, the high-throughput in vitro evaluation for such stereoisomerism-dependent hepatotoxicity is a critical challenge. In this study, we used a hepatic organoids-based in vitro hepatotoxic evaluation system in conjunction with using high content imaging to differentiate in vivo organ hepatotoxicity of the 2,3,5,4'-tetrahydroxy-trans-stilbene-2-O-ß-glucoside (trans-SG) and its cis-isomer (cis-SG). By using such an organoid platform, we successfully differentiated the two stereoisomers' hepatotoxic potentials, which were in accordance with their differences in rodents and humans. The lesion mechanism of the toxic isomer (cis-SG) was further found as the mitochondrial injury by high-content imaging, and its hepatotoxicity could be dose-dependently inhibited by the mitochondrial protective agent. These results demonstrated the utility of the organoids-based high-content imaging approach in evaluating and predicting organ toxicity of natural products in a low-cost and high-throughput way. It also suggested the rationale to use long-term cultured organoids as an alternative toxicology platform to identify early and cautiously the hepatotoxic new drug candidates in the preclinical phase.

Super Dominant Pathobiontic Bacteria in the Nasopharyngeal Microbiota Cause Secondary Bacterial Infection in COVID-19 Patients.

Coronavirus disease 2019 (COVID-19) is a respiratory infectious disease responsible for many infections worldwide. Differences in respiratory microbiota may correlate with disease severity. Samples were collected from 20 severe and 51 mild COVID-19 patients. High-throughput sequencing of the 16S rRNA gene was used to analyze the bacterial community composition of the upper and lower respiratory tracts. The indices of diversity were analyzed. When one genus accounted for >50% of reads from a sample, it was defined as a super dominant pathobiontic bacterial genus (SDPG). In the upper respiratory tract, uniformity indices were significantly higher in the mild group than in the severe group (P < 0.001). In the lower respiratory tract, uniformity indices, richness indices, and the abundance-based coverage estimator were significantly higher in the mild group than in the severe group (P < 0.001). In patients with severe COVID-19, SDPGs were detected in 40.7% of upper and 63.2% of lower respiratory tract samples. In patients with mild COVID-19, only 10.8% of upper and 8.5% of lower respiratory tract samples yielded SDPGs. SDPGs were present in both upper and lower tracts in seven patients (35.0%), among which six (30.0%) patients possessed the same SDPG in the upper and lower tracts. However, no patients with mild infections had an SDPG in both tracts. Staphylococcus, Corynebacterium, and Acinetobacter were the main SDPGs. The number of SDPGs identified differed significantly between patients with mild and severe COVID-19 (P < 0.001). SDPGs in nasopharyngeal microbiota cause secondary bacterial infection in COVID-19 patients and aggravate pneumonia. IMPORTANCE The nasopharyngeal microbiota is composed of a variety of not only the true commensal bacterial species but also the two-face pathobionts, which are one a harmless commensal bacterial species and the other a highly invasive and deadly pathogen. In a previous study, we found that the diversity of nasopharyngeal microbiota was lost in severe influenza patients. We named the genus that accounted for over 50% of microbiota abundance as super dominant pathobiontic genus, which could invade to cause severe pneumonia, leading to high fatality. Similar phenomena were found here for SARS-CoV-2 infection. The diversity of nasopharyngeal microbiota was lost in severe COVID-19 infection patients. SDPGs in nasopharyngeal microbiota were frequently detected in severe COVID-19 patients. Therefore, the SDPGs in nasopharynx microbiota might invade into low respiratory and be responsible for secondary bacterial pneumonia in patients with SARS-CoV-2 infection.

Exponential synchronization for variable-order fractional discontinuous complex dynamical networks with short memory via impulsive control.

This paper considers the exponential synchronization issue for variable-order fractional complex dynamical networks (FCDNs) with short memory and derivative couplings via the impulsive control scheme, where dynamical nodes are modeled to be discontinuous. Firstly, the mathematics model with respect to variable-order fractional systems with short memory is established under the impulsive controller, in which the impulse strength is not only determined by the impulse control gain, but also the order of the control systems. Secondly, the exponential stability criterion for variable-order fractional systems with short memory is developed. Thirdly, the hybrid controller, which consists of the impulsive coupling controller and the discontinuous feedback controller, is designed to realize the synchronization objective. In addition, by constructing Lyapunov functional and applying inequality analysis techniques, the synchronization conditions are achieved in terms of linear matrix inequalities (LMIs). Finally, two simulation examples are performed to verify the effectiveness of the developed synchronization scheme and the theoretical outcomes.

Supercritical CO2 extraction of fermented soybean lipids against erastin-induced ferroptosis in rat pheochromocytoma cells.

The optimum supercritical carbon dioxide (SC-CO2) extraction of fermented soybean lipids (FSE-C) was as follows: 35 °C, 30 MPa, and 2.40 ± 0.19% moisture content using response surface methodology. The fatty acid composition of FSE-C contained more palmitic acid and α-linolenic acid and less linoleic acid than unfermented soybean lipids (SE-C). FSE-C had higher contents of minor active components (phytosterols, squalene, total flavonoid, and total polyphenol) than SE-C. The protective effects of FSE-C on erastin-induced ferroptosis were investigated to reveal the potential mechanisms of action characterized by increasing cell viability and glutathione concentrations, attenuating levels of intracellular Fe2+ ion, lipid peroxidation, and ROS, as well as modifying mRNA expression (GPx4, SLC7A11, ACSL4, and LPCAT3) and lipid metabolism. These findings suggest that FSE-C is a class of active ingredients against erastin-induced ferroptosis and warrants further exploration and utilization as a functional food.

Cloning and expression analysis of DnMSI1 gene in orchid species Dendrobium nobile Lindl.

WD40 repeat proteins, the homologs of yeast MSI1, are conserved in plants, participating in protein complexes and playing fundamental functions in plant development. Although several MSI1-like proteins have been cloned and characterized in plants, the roles of MSI1-like proteins in the biennial ornamental plant, Dendrobium nobile Lindl, are still unclear. Here, we report the cloning of the DnMSI1 gene from Dendrobium nobile Lindl with RACE technology. We found that DnMSI1 expression was induced by GA3 and TDZ but inhibited by ABA, PP333, and drought and salt stress. Furthermore, DnMSI1 over-expression in Arabidopsis resulted in decreased tolerance to NaCl stress. These results suggest that DnMSI1 plays negative regulation roles in regulating salinity-stress resistance in Dendrobium nobile Lindl.