Coumarins and flavones with anti-inflammatory activity isolated from the branches and leaves of Daphne retusa.

In this study, two new (1, 13) and fourteen known (2-12, 14-16) compounds were isolated from the branches and leaves of Daphne retusa. On the basis of chemical evidence and spectral data analysis (UV, ECD NMR, and HR-ESI-MS), the structures of new compounds were elucidated. Furthermore, all compounds have been tested for their inhibitory effects on NO production in LPS-induced RAW 264.7 cells, and compound 3 showed obvious inhibitory effect. Through target screening and molecular docking technology, potential binding targets for compound 3 to exert anti-inflammatory effects have been predicted.

Metal Cation-Doped ns-Cucurbit[10]uril: Adsorption of Para-Phenylenediamine.

The separation of phenylenediamine (PDA) isomers is crucial in the field of chemical manufacturing. Herein, we presented a strategy for the separation of PDA isomers (para-phenylenediamine, p-PDA; meta-phenylenediamine, m-PDA; ortho-phenylenediamine, o-PDA) using four supramolecular framework materials of ns-cucurbit[10]uril (ns-Q[10]), (1) ns-Q[10](Cd), (2) ns-Q[10](Mn), (3) ns-Q[10](Cu), (4) ns-Q[10](Pb). Our findings indicated that these supramolecular framework materials of ns-Q[10] showed remarkable selectivity for para-phenylenediamine (p-PDA) in p-PDA, m-PDA, and o-PDA mixtures, respectively. The variations in selectivity observed in these four single-crystal structures arose from variations in the thermodynamic stabilities and binding modes of the host-guest complexes. Importantly, the supramolecular framework based on ns-Q[10] exhibited selective accommodation of p-PDA over its isomers. This study highlighted the practical application of ns-Q[10] in effectively separating PDA isomers and demonstrated the potential utility of ns-Q[10] in isolating other organic molecules.

Red Room-Temperature Phosphorescence Supramolecular Assemblies Based on Cucurbit[7]uril: Reversible Temperature Stimulation Response and Cell-Specific Silver Ion Imaging.

Solid-state materials with efficient room-temperature phosphorescence (RTP) emission have been widely used in materials science, and organic RTP-emitting systems with heavy-metal doping in aqueous solutions have attracted much attention in recent years. A novel supramolecular interaction was induced by host-guest assembly using cucurbit[7]uril (Q[7]) as the host and brominated naphthalimide phosphor as the guest. This interaction was further enhanced through synergistic chelation stimulated by analytical silver ion complexation. This approach facilitated the system's structural rigidity, intersystem crossing, and oxygen shielding. We achieved deep red phosphorescence emission in aqueous solution and ambient conditions along with quantitative determination of silver ions. The new complex exhibited good reversible thermoresponsive behavior and was successfully applied for the first time to target phosphorescence imaging of silver ions in the mitochondria of A549 cancer cells. These results are beneficial for constructing novel RTP systems with stimulus-responsive luminescence in aqueous solution, contributing to future research in bioimaging, detection, optical sensors, and thermometry materials.

Ginsenoside Rg1 in neurological diseases: From bench to bedside.

Ginseng has been used in China as a superior medicinal material for thousands of years that can nourish the five internal organs, calm the mind and benefit wisdom. Due to its anti-inflammatory, antioxidant and neuroprotective activities, one of the active components of ginseng, ginsenoside Rg1, has been extensively investigated in the remedy of brain disorders, especially dementia and depression. In this review, we summarized the research progress on the action mechanisms of Rg1 ameliorating depression-like behaviors, including inhibition of hyperfunction of hypothalamic-pituitary-adrenal (HPA) axis, regulation of synaptic plasticity and gut flora. Rg1 may alleviate Alzheimer's disease in the early phase, as well as in the middle-late phases through repairing dendrite, axon and microglia- and astrocyte-related inflammations. We also proposed that Rg1 could regulate memory state (the imbalance of working and aversive memory) caused by distinct stimuli. These laboratory studies would further the clinical trials on Rg1. From the prospective of drug development, we discussed the limitations of the present investigations and proposed our ideas to increase permeability and bioavailability of Rg1. Taken together, Rg1 has the potential to treat neuropsychiatric disorders, but a future in-depth investigation of the mechanisms is still required. In addition, drug development will benefit from the clinical trials in one specific neuropsychiatric disorder.

Three New Labdane-Type Diterpenoids from the Fruits of Amomum villosum and Their Anti-Inflammatory Activities.

Three new labdane-type diterpenoids, calcaratarin E, villosumtriol, and 12-epi-villosumtriol (1-3) were isolated from the fruits of Amomum villosum, along with seven known diterpenoids (4-10). Through comprehensive analysis of chemical evidence and spectral data including UV, 1D and 2D NMR, HR-ESI-MS, IR, and X-ray crystallography, the structures of these novel compounds were successfully determined. Additionally, the inhibitory effects of compounds 2-10 on NO production in lipopolysaccharide (LPS)-induced RAW264.7 cells were evaluated. Notably, compound 6 exhibited the most significant inhibitory effect with an IC50 value of 1.74±0.69 µM.

Natural withanolides, an update.

Covering: March 2010 to December 2020. Previous review: Nat. Prod. Rep., 2011, 28, 705This review summarizes the latest progress and perspectives on the structural classification, biological activities and mechanisms, metabolism and pharmacokinetic investigations, biosynthesis, chemical synthesis and structural modifications, as well as future research directions of the promising natural withanolides. The literature from March 2010 to December 2020 is reviewed, and 287 references are cited.

CdS-Based Catalysts Derived from TMeQ[6]/[CdxCly]n--Based Frameworks for Oxidation Benzylamine.

The anion-induced outer surface interaction of Q[n]s is an important driving force in the construction of Q[n]-based supramolecular frameworks. In this work, a symmetric tetramethyl-substituted cucurbit[6]uril (TMeQ[6]) is selected as the basic structural block. Using the anion-induced outer surface interaction of Q[n]s derived from [CdxCly]n- anions formed by Cd2+ cations in a HCl medium, four different TMeQ[6]-[CdxCly]n--based supramolecular frameworks are constructed. Three of the most common TMeQ[6]-[CdxCly]n--based supramolecular frameworks are selected for further vulcanization, and three different CdS/TMeQ[6]-based framework catalysts with different structures and properties are obtained. The catalytic activities of these three CdS/TMeQ[6]-based framework catalysts are investigated by the coupling photocatalytic reaction of aminobenzyl, and the results showed that the catalytic activities of the three catalysts are all higher than that of pure CdS. Therefore, this work establishes that it is possible to establish a method for synthesizing the Q[n]-based framework-supported catalysts by first synthesizing TMeQ[6]-[CdxCly]n--based supramolecular frameworks and then forming Q[n]-based framework supported catalysts by sulfurization or reduction.

Two New Nor-seco-Isodhilarane-Type Meroterpenoids from the Endophytic Fungus Penicillium purpurogenum.

Two new nor-seco isodhilarane meroterpenoids (NSIMs), purpurogenolides F (1) and G (2), along with three known meroterpenoid analogs (3-5), were isolated from the cultures of an endophytic fungus, Penicillium purpurogenum. Structures and absolute configurations of the new NSIMs were determined based on extensive spectroscopic data analyses, including HR-ESI-MS, UV, IR, NMR chemical shift calculations together with DP4+ probability analysis, as well as ECD calculations. All the isolated meroterpenoids were assessed for their anti-inflammatory activities, and compound 4 exhibited moderate inhibitory activity against the nitric oxide (NO) production in lipopolysaccharide (LPS) induced RAW 264.7 cells with an IC50 value of 20.85±2.31 µM.

[Lignans from Agrimonia pilosa].

Thirteen lignans were isolated from 60% ethanol extract of Agrimonia pilosa by column chromatography over silica gel, ODS, and MCI and preparative high performance liquid chromatography(HPLC). Their chemical structures were identified by physiochemical properties and spectral data as(7S,8S)-threo-4,7,9,9'-tetrahydroxy-3,3',5'-trimethoxy-8-O-4'-neolignan(1),(+)-4,9,9'-trihydroxy-3-methoxy-3',7-epoxy-8,4'-oxyneolignan(2), dihydrodehydro-diconiferyl alcohol(3), 4,9,9'-trihydroxy-3,3',5-trimethoxy-4',7-epoxy-8,5'-neolignan(4),(-)-secoisolariciresinol(5), 4,7,9,9'-tetrahydroxy-3,3',5'-trimethoxy-8-O-4'-neolignan(6),(+)-isolariciresinol(7), 4,7,9,9'-tetrahydroxy-3,3'-dimethoxy-8-O-4'-neolignan(8), burselignan(9),(-)-evofolin B(10), icariol A2(11), ciwujiatone(12), and(+)-4″,4-dihydroxy-3,3',3″,3,5,5'-hexamethoxy-7,9';7',9-diepoxy-4,8″;4',8-bisoxy-8,8'-dineolignan-7″,7,9″,9-tetraol(13). Compound 1 was a new compound, and compounds 1-13 were isolated from Agrimonia plant for the first time. This study can enrich the chemical components in A. pilosa and provide material conditions for the follow-up study of its biological activity and the elucidation of its pharmacodynamic substances.

Withanolides isolated from Tubocapsicum anomalum and their antiproliferative activity.

Seven undescribed withanolides (1-7) and six artificial withanolides (8-13), along with 20 known compounds (14-33) were isolated from the aerial parts of Tubocapsicum anomalum. Their structures were confirmed by comprehensive spectroscopic analyses. The absolute configuration of compound 1 was defined by single-crystal X-ray crystallography. All isolates were evaluated for their antiproliferative effects against five human tumor cell lines (Hep3B, MDA-MB-231, SW480, HCT116 and A549), among which compound 24 (tubocapsanolide A) exhibited the highest activities against the MDA-MB-231 cells with an IC50 value of 1.89 ± 1.03 µM. Further studies showed that 24 exhibited significant damage to mitochondria in MDA-MB-231 cells, including excess reactive oxygen species, decreased mitochondrial membrane potential, and apoptosis initiation. In addition, compound 24 also inhibited cell migration. These findings show that tubocapsanolide A may be a promising molecule for triple-negative breast cancer treatment and merit further evaluation.

Cucurbit[n]uril-Based Supramolecular Frameworks Assembled through Outer-Surface Interactions.

Porous materials, especially metal-organic frameworks, covalent organic frameworks, and supramolecular organic frameworks, are widely used in heterogeneous catalysis, adsorption, and ion exchange. Cucurbit[n]urils (Q[n]s) suitable building units for porous materials because they possess cavities with neutral electrostatic potential, portal carbonyls with negative electrostatic potential, and outer surfaces with positive electrostatic potential, which may result in the formation of Q[n]-based supramolecular frameworks (QSFs) assembled through the interaction of guests within Q[n]s, the coordination of Q[n]s with metal ions, and outer-surface interaction of Q[n]s (OSIQ). This review summarizes the various QSFs assembled via OSIQs. The QSFs can be classified as being assembled by 1) self-induced OSIQ, 2) anion-induced OSIQ, and 3) aromatic-induced OSIQ. The design and construction of QSFs with novel structures and specific functional properties may establish a new research direction in Q[n] chemistry.

A novel 15-spiro diterpenoid dimer from Andrographis paniculata with inhibitory potential against human carboxylesterase 2.

The phytochemical investigation of Andrographis paniculata resulted in the isolation of a novel 15-spiro diterpenoid dimer bisandrographolide G (1). Its structure was determined by 1D and 2D NMR, HRESIMS, electronic circular dichroism (ECD), and TD DFT calculations of ECD spectra. It showed potent inhibitory activity against human carboxylesterase 2 (CES 2) with an IC50 value of 4.61 ± 0.23 µM, and it was defined as a mixed-competitive type inhibitor with a Ki value of 8.88 µM based on the inhibition kinetics result. This finding gave us a hit to develop new generation of human CES 2 inhibitors.

Triterpenoids from Anchusa italica and their protective effects on hypoxia/reoxygenation induced cardiomyocytes injury.

Six new triterpenoids (1-6) and 22 known analogues (7-28), were separated from the aerial parts of Anchusa italica Retz., a traditional Uygur medicine for treating cardiovascular and cerebrovascular diseases in the Xinjiang region, China. The possible effects of compounds 1-28 on hypoxia/reoxygenation (H/R) induced cardiomyocytes injury were assayed, and compounds 4, 6-17, 21-22 and 26-28 showed significant protective effects. Further, the representative new compound 6 significantly suppressed the levels of H/R-induced apoptosis and autophagy in neonatal rat cardiomyocytes, with the reversing of the downregulated expression of Bcl-2 and upregulated expression of Bax and Beclin-1 by compound 6 treatment in neonatal rat cardiomyocytes following H/R injury. In addition, compound 6 protected cardiomyocyte from H/R injury, and pretreatment with 6 could decrease CK and LDH levels. Compound 6 also alleviated H/R-induced phosphorylation of p38 MAPK in neonatal rat cardiomyocytes. Therefore, tripterpenoid 6 and its analogues may be the pharmacodyamic material of A. italica, and offer a promising therapeutic approach for treating cardiomyocyte injury induced by H/R.

Numerical Study on the Characteristics of Boger Type Viscoelastic Fluid Flow in a Micro Cross-Slot under Sinusoidal Stimulation.

The cross-slot geometry plays an important role in the study of nonlinear effects of viscoelastic fluids. The flow of viscoelastic fluid in a micro cross-slot with a high channel aspect ratio (AR, the ratio of channel depth to width) can be divided into three types, which are symmetric flow, steady-state asymmetric flow and time-dependent flow under the inlet condition with a constant velocity. However, the flow pattern of a viscoelastic fluid in the cross-slot when a stimulation is applied at inlets has been rarely reported. In this paper, the response of cross-slot flow under an external sinusoidal stimulation is studied by numerical simulations of a two-dimensional model representing the geometry with a maximum limit of AR. For the cases under constant inlet velocity conditions, three different flow patterns occur successively with the increase of Weissenberg number (Wi). For the cases under sinusoidal varying inlet velocity conditions, when the stimulation frequency is far away from the natural frequency of a viscoelastic fluid, the frequency spectrum of velocity fluctuation field shows the characteristics of a fundamental frequency and several harmonics. However, the harmonic frequency disappears when the stimulation frequency is close to the natural frequency of the viscoelastic fluid. Besides, the flow pattern shows spatial symmetry and changes with time. In conclusion, the external stimulation has an effect on the flow pattern of viscoelastic fluid in the 2D micro cross-slot channel, and a resonance occurs when the stimulation frequency is close to the natural frequency of the fluid.

Unique Topology Analysis by ToposPro for a Metal-Organic Framework with Multiple Coordination Centers.

The reactions of 2-(4-pyridyl) thiazole-4-carboxylic acid (Hptca) and CuCl2·6H2O have led to a novel 3D mixed-valence, four-copper-center, metal-organic framework (MOF) [Cu8Cl2(ptca)10·17H2O] n (1). The topology analysis using ToposPro software package for 1 resulted in three chain-based topology types of sra (42, 63, 8), pcu (412, 63), and dia (66) via choosing corresponding connection atoms as central atoms. The study indicates that connection atoms associated directly with multiple coordination centers are applicable to act as central atoms. This unique topology analysis approach is conceptually different from the current analytical methods which use node atoms as central atoms. In addition, complex 1 exhibits significant selective adsorption of CO2 over N2. This study provides a great example of the topological analysis of MOFs with multiple coordination centers.

Telbivudine can safely reduce mother-to-child transmission in chronic hepatitis B women after 12 weeks of gestation.

BACKGROUND: To evaluate the efficacy and safety of telbivudine in chronic hepatitis B women during the second and third trimesters of pregnancy. METHODS: The week 12-34 of pregnant women were screened in this prospective non-intervention study, with HBV DNA > 106 IU/mL and alanine aminotransferase > 50 IU/L. The patients were received telbivudine treatment as a treatment group or without antiviral treatment as a control group. All infants were received recombinant hepatitis B vaccine 10 µg within 12 h of birth, at week 4 and week 24, immunoglobulin G within 12 h of birth and were detected HBV markers at the range from 7 to 12 months after delivery. RESULTS: A total of 241 patients were finally enrolled, 139 patients in telbivudine group and 102 patients in control group. HBsAg negative rate of infants was 99.3% (135/136) in telbivudine group and was 91.9% (91/99) in control group after 7 months (P = 0.005), respectively. The incidence of undetectable HBV DNA levels (47.5%) was significantly lower in telbivudine-treated mothers than that in the controls (0%), and 75.5% patients alanine aminotransferase returned to normal in telbivudine group, and 51% in control group at delivery (P < 0.001), respectively. CONCLUSIONS: Telbivudine can safely reduce mother-to-child transmission in chronic hepatitis B women after 12 weeks of gestation.

Anti-inflammatory Lathyrane Diterpenoids from Euphorbia lathyris.

Six new lathyrane diterpenoids (1-6) and 10 known analogues (7-16), were separated from the seeds of Euphorbia lathyris. The absolute configuration of 1 was determined by X-ray crystallography, and the C-2' configuration of 5 was elucidated by comparing experimental and calculated ECD data. These compounds were studied for their inhibition against nitric oxide (NO) generation induced by lipopolysaccharide in RAW264.7 macrophage cells. Compounds 1-3, 7, 9, 11, 13, 14, and 16 displayed inhibitory effects on NO production, with IC50 values of 2.6-26.0 µM. The new compound 1 (IC50 3.0 ± 1.1 µM), with no obvious cytotoxicity, was selected for further experiments. The production of cytokines such as IL-6 and IL-1ß, as well as the protein expression of iNOS, NF-κB, and phosphorylated IκBα, was reduced by 1 dose-dependently. These results suggested that lathyrane diterpenoids may be used as potential anti-inflammatory agents and are worth being further researched.

Physapubescin I from husk tomato suppresses SW1990 cancer cell growth by targeting kidney-type glutaminase.

Kidney-type glutaminase (KGA), catalyzing the hydrolysis of glutamine to glutamate for energy supply, is over-expressed in many cancers and has been regarded as a new therapeutic target for cancers. Physapubescin I was isolated from the fruits of the edible herb Physalis pubescens L., commonly named as "husk tomato or hairy groundcherry", and was predicted to be a potential KGA inhibitor through structure-based virtual ligand screening. Enzyme inhibition assays, microscale thermophoresis (MST) and cellular thermal shift assay (CETSA) experiments have demonstrated the high efficiency and specificity of physapubescin I targeting KGA. EdU proliferation, Hoechst 33258 staining and cytotoxicity assays indicated that physapubescin I could inhibit cancer cell proliferation and promote apoptosis more effectively than the known KGA inhibitor, BPTES. Knockdown of KGA by siRNA reduced the inhibition of physapubescin I to SW1990 cells. Meanwhile, physapubescin I impaired glutamine metabolism in SW1990 cells with increasing intracellular level of glutamine, and correspondingly decreasing glutamate and its downstream metabolites, which may account for its inhibition of cancer cell proliferation and proapoptosis. Physapubescin I also showed significant tumor growth inhibition and low toxicity in a SW1990 xenograft mouse model. Collectively, physapubescin I may serve as a potential drug candidate or lead compound for cancer therapy by targeting KGA.

Erratum: Chen, L.X., et al. Synthesis and Structure of the Inclusion Complex {NdQ[5]K@Q[10](H2O)4}•4NO3•20H2O. Molecules 2017, 22, 1147.

The authors wish to make the following correction to their paper [...].

Richards-Campbell sleep questionnaire: psychometric properties of Chinese critically ill patients.

BACKGROUND: Sleep abnormalities occur frequently in critically ill patients. Nurses are strategically placed, specifically in intensive care units, to promote sleep in such patients. Currently, an effective sleep assessment tool in Chinese is not available for intensive care settings. AIM: This study aimed to assess the reliability and validity of the Chinese version of the Richards-Campbell Sleep Questionnaire (RCSQ-C). It also aimed to evaluate patient-nurse reliability and agreement of the RCSQ-C in the intensive care unit (ICU). METHODS: We translated the original RCSQ into Chinese and then back-translated it into English to ensure its accuracy of translation. Internal consistency, discrimination validity and construct validity of the RCSQ-C were examined in 150 critically ill patients. The convergent validity of the RCSQ-C was evaluated in 44 of 150 critically ill patients, and data from the RCSQ-C were compared with those of the Chinese version of St Mary's Hospital Sleep Questionnaire (SMHSQ). Comparisons were also made between RCSQ-C scores obtained from patients and their nurses. RESULTS: Cronbach's α of the RCSQ-C was 0.923; thus, it showed high reliability. The corrected item-total correlation coefficient was in the range of 0·680∼0·805, which showed that the items were homogeneous for evaluating sleep. The content validity was 0·84. One factor was extracted with a cumulative contribution rate of 76·597%. Confirmatory factor analysis showed that the original single-factor structure proposed by Richards adequately fit the data. The RCSQ-C could discriminate poor and good sleepers, which supported discriminant validity. There was a close correlation between the scores obtained from the RCSQ patient's version and those from the SMHSQ. The intraclass correlation coefficients of the patient and nurse ranged from 0·315 to 0·609. CONCLUSIONS: The psychometric properties of the RCSQ-C suggest its utility in critically ill patients. Patient-nurse reliability on the RCSQ-C was "fair" to "substantial", with nurses tending to overestimate patients' perceived sleep quality. RELEVANCE TO CLINICAL PRACTICE: If the validity of this questionnaire is supported in other ICU samples, RCSQ-C could be used as a routine evaluation instrument to distinguish good and poor sleepers and then direct nurses to form corresponding treatment plans to promote sleep.