Unraveling quantum coherences mediating primary charge transfer processes in photosystem II reaction center.

Photosystem II (PSII) reaction center (RC) is a unique complex that is capable of efficiently separating electronic charges across the membrane. The primary energy- and charge-transfer (CT) processes occur on comparable ultrafast timescales, which makes it extremely challenging to understand the fundamental mechanism responsible for the near-unity quantum efficiency of the transfer. Here, we elucidate the role of quantum coherences in the ultrafast energy and CT in the PSII RC by performing two-dimensional (2D) electronic spectroscopy at the cryogenic temperature of 20 kelvin, which captures the distinct underlying quantum coherences. Specifically, we uncover the electronic and vibrational coherences along with their lifetimes during the primary ultrafast processes of energy and CT. We construct an excitonic model that provides evidence for coherent energy and CT at low temperature in the 2D electronic spectra. The principles could provide valuable guidelines for creating artificial photosystems with exploitation of system-bath coupling and control of coherences to optimize the photon conversion efficiency to specific functions.

Structure-Guided Discovery of Diverse Cytotoxic Dimeric Xanthones/Chromanones from Penicillium chrysogenum C-7-2-1 and Their Interconversion Properties.

Xanthone-chromanone homo- or heterodimers are regarded as a novel class of topoisomerase (Topo) inhibitors; however, limited information about these compounds is currently available. Here, 14 new (1-14) and 6 known tetrahydroxanthone chromanone homo- and heterodimers (15-20) are reported as isolated from Penicillium chrysogenum C-7-2-1. Their structures and absolute configurations were unambiguously demonstrated by a combination of spectroscopic data, single-crystal X-ray diffraction, modified Mosher's method, and electronic circular dichroism analyses. Plausible biosynthetic pathways are proposed. For the first time, it was discovered that tetrahydroxanthones can convert to chromanones in water, whereas chromone dimerization does not show this property. Among them, compounds 5, 7, 8, and 16 exhibited significant cytotoxicity against H23 cell line with IC50 values of 6.9, 6.4, 3.9, and 2.6 µM, respectively.

Electronanofiltration Membranes with a Bilayer Charged Structure Enable High Li+/Mg2+ Selectivity.

Achieving separation of lithium and magnesium with similar radii is crucial for the current lithium extraction technology from salt lakes, which usually possess a high lithium-to-magnesium ratio. Herein, we proposed the facile sequential interfacial polymerization (SIP) approach to construct electronanofiltration membranes (ENFMs) with a bilayer charged structure consisting of a high positively charged surface and a negatively charged sublayer. The trimesoyl chloride (TMC) concentration was adjusted to enhance the -COOH content and negative charge of the polyamide sublayer to promote Li+ migration, and then the quaternized polyethylenimine was introduced to the membrane surface by the SIP process to increase the positive charge density on the surface of the ENFMs, which would block the migration of Mg2+ and enhance the Li+/Mg2+ selectivity of the ENFMs. The optimal quaternary-modified ENFMs achieved outstanding selectivity for Li+/Mg2+ (49.85) and high Li+ flux (4.10 × 10-8 mol cm-2 s-1) at a current density of 10 mA cm-2. Moreover, in simulated brines with low lithium concentration and high Mg2+/Li+ ratio, the optimal ENFMs also displayed elevated Li+/Mg2+ selectivity (>45), highlighting the substantial promise of the membranes for practical applications.

New cassane-type alkaloids and diterpenoids from the pericarps of Caesalpinia bonduc.

The phytochemical investigation of the pericarps of Caesalpinia bonduc led to the isolation and identification of five new cassane-type alkaloids: caesalminines C - G (1-5) and six new diterpenoids: caesalbonducin K - P (6-11), along with seven known compounds (12-18). Compounds 1-5 were identified as a group of rare alkaloids possessing a tetracyclic cassane-type diterpenoid skeleton with a lactam D-ring instead of a typical furan or lactone moiety. The structures of 1-11 were elucidated on the basis of 1D and 2D NMR including HSQC, HMBC, COSY and NOESY, and other spectroscopic analyses. The cytotoxic activities of the isolated compounds were evaluated in the A431, A549 and U87MG cancer cell lines.

Erratum: Long non-coding RNA DANCR stabilizes HIF-1α and promotes metastasis by interacting with NF90/NF45 complex in nasopharyngeal carcinoma: Erratum.

[This corrects the article DOI: 10.7150/thno.28538.].

New Monoterpenoid Indole Hybrids from Gelsemium elegans with Anti-Inflammatory and Osteoclast Inhibitory Activities.

Gelsegansymines A (1) and B (2), two new indole alkaloids along with six known analogues (3-8) were isolated from the aerial parts of Gelsemium elegans. Their structures were elucidated by means of spectroscopic techniques. Structurally, compounds 1 and 2 possessed the rare cage-like gelsedine skeleton hybrid with bicyclic monoterpenoid. The anti-inflammatory activities of isolated compounds (1-3) were tested on LPS induced RAW264.7 cells. Under the treated concentration without toxicity for cells, the cytokines levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were evaluated by Griess method and enzyme-linked immunosorbent assay (ELISA). The results showed that compounds 1-3 exhibited anti-inflammatory activities with dose-dependent manner range from 12.5 to 50 µmol/L. Furthermore, the inhibitory activities of compounds 1 and 2 on receptor activator of NF-κB ligand (RANKL) induced osteoclast formation were tested in vitro. Compounds 1 and 2 at 5 µmol/L exhibited the significant inhibitory effect on the osteoclastogenesis induced by RANKL. This work reported the anti-inflammatory and osteoclast inhibitory activities of new monoterpenoid indole hybrids, which may inspire the further light on the related traditional application research of G. elegans.

Genus Gelsemium and its Endophytic Fungi - Comprehensive Review of their Traditional Uses, Phytochemistry, Pharmacology, and Toxicology.

BACKGROUND: The use of ethnic medicinal plants has revitalized wide popularity in Africa, Asia, and most of the world because of the energy consumption barriers increase of synthetic drugs. Gelsemium is a traditional genus of plants with famous cultural and medicinal significance in Southeast Asia and North America. Three species are reported from the genus Gelsemium, including Gelsemium elegans (Gardn. & Camp.) Benth., Gelsemium sempervirens (L.) J.St.-Hil., and Gelsemium rankinii Small. Among them, G. elegans is well known for its toxicity and is used as a traditional remedy for skin problems, neuralgia, fractures, and cancer. The first record of the toxic medicine G. elegans is the Chinese herbal medicine classically known as Shen-Nong Ben-Cao Jing. In the legend, the Shennong emperor was poisoned by G. elegans, hence, it is also wellknown as Duan Chang Cao in China. In addition, G. sempervirens tincture is also used in the treatment of inflammation of the spinalcolumn, and diminishes blood to the cerebrospinal centers. INTRODUCTION: This review aims to provide up-to-date information on Gelsemium and its endophytic fungi on their traditional uses, phytochemistry, pharmacology, and toxicology. Mechanism studies regarding the detoxification profile of Gelsemium are also reviewed. METHODS: For this updated review, the literature survey and search were performed on the scientific databases PubMed, ScienceDirect, Wiley, China CNKI, Web of Science, SciFinder, and Google Scholar using the relevant keywords. RESULTS: The plants of the genus Gelsemium are all reported as rich sources of monoterpene indole alkaloids. Previous phytochemical studies published more than 200 alkaloids from Gelsemium and its endophytic fungi, which have attracted considerable attention from pharmaceutists and phytochemists due to their diverse and complex structures. The bioactivities of Gelsemium phytoconstituents studied using various chemical methods are summarized and described herein. Considering the huge influence of Gelsemium regarding its traditional applications, the activities of isolated compounds were focused on the anti-tumor, anti-inflammatory, analgesic and antianxiety, immunostimulatory, and immunosuppressive properties, which provide evidence supporting the ethnopharmacological effectiveness of the genus Gelsemium. Unlike all previous reviews of genus Gelsemium, to the best of our knowledge, the recently reported natural products from its endophytic fungi are first time summarized in this review. CONCLUSION: It is clearly suggested from the literature information that the structures and biological activities of Gelsemium have a wide range of attraction from folk to the community of scholars. However, as a highly toxic genus, the work on the detoxification mechanism and toxicology of Gelsemium is urgently needed before entering clinical research. It is noteworthy that the discussion about the relationship between structural and biological activities are a valuable topic of expectation, while the structural modification for active or toxic components may shed light on toxicological breakthrough. Besides the compounds from the plants of genus Gelsemium, the recently reported natural products from its endophytic fungi may provide a supplement for its ethnomedicinal uses and ethnological validity.

Hydrogen sulfide antagonizes formaldehyde-induced ferroptosis via preventing ferritinophagy by upregulation of GDF11 in HT22 cells.

Formaldehyde (FA) has neurotoxic characteristics and causes neurodegenerative disease. Our previous study demonstrated the neuroprotective effects of hydrogen sulfide (H2S) on FA-induced neurotoxicity in HT22 cells. Emerging evidence have supported that ferroptosis is involved in FA-induced neurotoxicity. To understand the mechanism of the protection of H2S against FA-induced neurotoxicity, this study explored the regulatory effect of H2S on FA-induced ferroptosis and the underlying mechanisms. The researcher found that H2S (100, 200, and 400 µM, 30 min) reverses the ferroptosis induced by FA (100 µM, 24 h) in HT22 cells (a cell line of mouse hippocampal neurons), including decreases in free iron, reactive oxygen species (ROS), 4-hydroxy-2-trans-nominal (4-HNE), and malondialdehyde (MDA) contents, as well as an increase in glutathione (GSH) content. H2S (100, 200, and 400 µM, 30 min) also inhibited ferritinaphagy in FA-exposed HT22 cells, as evidenced by the downregulation of the ferritinophagy receptor nuclear receptor coactivator 4 (NCOA4) and microtubule-associated protein 1 light chain-3B (LC3B) as well as the upregulation of the main iron storage protein ferritin heavy chain 1 (FTH1) and p62. H2S (100, 200, and 400 µM, 30 min) also up-regulated the expression of growth differentiation factor-11 (GDF11) in FA-exposed HT22 cells. Furthermore, knockdown of GDF11 in HT22 cells cancelled the beneficial effects of H2S in FA-induced ferroptosis and ferritinaphagy. These data indicated that the protective mechanism underlying H2S-prevented neurotoxicity of FA is involved in alleviating FA-induced ferroptosis via inhibiting ferritinaphagy by upregulation of GDF11.

Structural Elucidation and Cytotoxic Activity of New Monoterpenoid Indoles from Gelsemium elegans.

Two new monoterpenoid indole alkaloids, gelselegandines F (1) and G (2), were isolated from the aerial parts of Gelsemium elegans. Their structures were elucidated by means of spectroscopic techniques and quantum chemical calculations. The ECD calculations were conducted at the B3LYP/6-311G(d,p) level and NMR calculations were carried out using the Gauge-Including Atomic Orbitals (GIAO) method. Structurally, the two new compounds possessed rare, cage-like, monoterpenoid indole skeletons. All isolated compounds and the total alkaloids extract were tested for cytotoxicity against four different tumor cell lines. The total alkaloids extract of G. elegans exhibited significant antitumor activity with IC50 values ranging from 32.63 to 82.24 ug/mL. In order to discover anticancer leads from the active extraction, both new indole compounds (1-2) were then screened for cytotoxicity. Interestingly, compound 2 showed moderate cytotoxicity against K562 leukemia cells with an IC50 value of 57.02 uM.

Identification of Bletilla striata and related decoction pieces: a data fusion method combining electronic nose, electronic tongue, electronic eye, and high-performance liquid chromatography data.

Introduction: We here describe a new method for distinguishing authentic Bletilla striata from similar decoctions (namely, Gastrodia elata, Polygonatum odoratum, and Bletilla ochracea schltr). Methods: Preliminary identification and analysis of four types of decoction pieces were conducted following the Chinese Pharmacopoeia and local standards. Intelligent sensory data were then collected using an electronic nose, an electronic tongue, and an electronic eye, and chromatography data were obtained via high-performance liquid chromatography (HPLC). Partial least squares discriminant analysis (PLS-DA), support vector machines (SVM), and back propagation neural network (BP-NN) models were built using each set of single-source data for authenticity identification (binary classification of B. striata vs. other samples) and for species determination (multi-class sample identification). Features were extracted from all datasets using an unsupervised approach [principal component analysis (PCA)] and a supervised approach (PLS-DA). Mid-level data fusion was then used to combine features from the four datasets and the effects of feature extraction methods on model performance were compared. Results and Discussion: Gas chromatography-ion mobility spectrometry (GC-IMS) showed significant differences in the types and abundances of volatile organic compounds between the four sample types. In authenticity determination, the PLS-DA and SVM models based on fused latent variables (LVs) performed the best, with 100% accuracy in both the calibration and validation sets. In species identification, the PLS-DA model built with fused principal components (PCs) or fused LVs had the best performance, with 100% accuracy in the calibration set and just one misclassification in the validation set. In the PLS-DA and SVM authenticity identification models, fused LVs performed better than fused PCs. Model analysis was used to identify PCs that strongly contributed to accurate sample classification, and a PC factor loading matrix was used to assess the correlation between PCs and the original variables. This study serves as a reference for future efforts to accurately evaluate the quality of Chinese medicine decoction pieces, promoting medicinal formulation safety.

Rose Bengal inhibits ß-amyloid oligomers-induced tau hyperphosphorylation via acting on Akt and CDK5 kinases.

RATIONALE: Tau hyperphosphorylation and aggregation is considered as a main pathological mechanism underlying Alzheimer's disease (AD). Rose Bengal (RB) is a synthetic dye used for disease diagnosis, which was reported to inhibit tau toxicity via inhibiting tau aggregation in Drosophila. However, it was unknown if RB could produce anti-AD effects in rodents. OBJECTIVES: The research aimed to investigate if and how RB could prevent ß-amyloid (Aß) oligomers-induced tau hyperphosphorylation in rodents. METHODS AND RESULTS: RB was tested in vitro (0.3-1 µM) and prevented Aß oligomers-induced tau hyperphosphorylation in PC12 cells. Moreover, RB (10-30 mg/kg, i.p.) effectively attenuated cognitive impairments induced by Aß oligomers in mice. Western blotting analysis demonstrated that RB significantly increased the expression of pSer473-Akt, pSer9-glycogen synthase kinase-3ß (GSK3ß) and reduced the expression of cyclin-dependent kinase 5 (CDK5) both in vitro and in vivo. Molecular docking analysis suggested that RB might directly interact with GSK3ß and CDK5 by acting on ATP binding sites. Gene Ontology enrichment analysis indicated that RB might act on protein phosphorylation pathways to inhibit tau hyperphosphorylation. CONCLUSIONS: RB was shown to inhibit tau neurotoxicity at least partially via inhibiting the activity of GSK3ß and CDK5, which is a novel neuroprotective mechanism besides the inhibition of tau aggregation. As tau hyperphosphorylation is an important target for AD therapy, this study also provided support for investigating the drug repurposing of RB as an anti-AD drug candidate.

Effect of erbium family laser etching on shear bond strength of enamel surfaces: A meta-analysis-PRISMA.

BACKGROUND: Recently, laser etching has appealed to people's attention. It is meaningful to compare the effect of erbium-doped yttrium-aluminum-garnet (Er:YAG) and erbium-chromium; yttrium-scandium-gallium-garnet (Er,Cr:YSSG) laser etching parameters with acid etching on bond strength of enamel surfaces. As far as we know, there still remains no related meta-analysis. To evaluate the efficacy of Er:YAG and Er,Cr:YSSG lasers etching on shear bond strength (SBS) of brackets bonded to enamel. The meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, conducted with literature search. METHODS: Twelve relevant randomized controlled trials (RCTs) were included. RESULTS: The pooled analysis of SBS showed that there were no significant differences between erbium family lasers and acid etching. In the mass, we noticed they did not achieve statistical significance in the lasers etching and acid etching. However, pooled analysis of 5 studies showed the SBS bonding to enamel was lower in Er,Cr:YAG laser group compared with acid group. As a whole, there were statistical significance between erbium lasers groups and acid etching group in adhesive remnant index (ARI) aspects, which less adhesives remained can reduce damage to enamel. With regard to the rate of teeth with ARI score ≤2, the results in Er:YAG laser etching group were obviously higher than acid etching group. CONCLUSION: Our data indicated that erbium lasers may be considered bonding of brackets to enamel instead of acid etching bonding to enamel.

Biological Activities and Secondary Metabolites from Sophora tonkinensis and Its Endophytic Fungi.

The roots of Sophora tonkinensis Gagnep., a traditional Chinese medicine, is known as Shan Dou Gen in the Miao ethnopharmacy. A large number of previous studies have suggested the usage of S. tonkinensis in the folk treatment of lung, stomach, and throat diseases, and the roots of S. tonkinensis have been produced as Chinese patent medicines to treat related diseases. Existing phytochemical works reported more than 300 compounds from different parts and the endophytic fungi of S. tonkinensis. Some of the isolated extracts and monomer compounds from S. tonkinensis have been proved to exhibit diverse biological activities, including anti-tumor, anti-inflammatory, antibacterial, antiviral, and so on. The research progress on the phytochemistry and pharmacological activities of S. tonkinensis have been systematically summarized, which may be useful for its further research.

Intravenous immunoglobulin for interstitial lung diseases of anti-melanoma differentiation-associated gene 5-positive dermatomyositis.

OBJECTIVE: Rapidly progressive interstitial lung disease (RP-ILD) in DM patients positive for anti-melanoma differentiation-associated gene 5 (anti-MDA5) autoantibody (MDA5-DM) often have a poor prognosis, frequently fatal. As there is a scarcity of data regarding the effect of intravenous immunoglobulin (IVIG) on RP-ILD in MDA5-DM patients (MDA5-RPILD), we conducted this study to determine the efficacy of a IVIG add-on initial treatment. METHODS: Patients with newly-onset MDA5-RPILD from September 2018 to June 2020 were retrospectively reviewed for 6 months in the First Affiliated Hospital of Zhengzhou University. They were divided into two groups: IVIG and non-IVIG groups. The major measurement of treatment outcome was the difference in the mortality in 3-month and 6-month between two group patients. Other relevant indicators were also recorded, including the incidence of infection, the dosages of GCs, the remission rate and the variables in laboratory data. RESULTS: The IVIG group (n = 31) showed significantly lower 6-month mortality rate than the non-IVIG group (n = 17) (22.6% vs 52.9%; P =0.033). The IVIG group patients had a higher remission rate at 3 months (71.0% vs 41.2%; P =0.044). Gradual reduction was observed in the first 3 months with regard to the titre of anti-MDA5 autoantibody, the serum level of ferritin and the ground glass opacification GGO scores. CONCLUSION: IVIG adjunct therapy is a very effective first-line treatment for patients with MDA5-RPILD. IVIG may increase the survival and remission rate by lowering ferritin concentration, anti-MDA5 titre and GGO score.

[Allergen Analysis of 4622 Children with Allergic Diseases in Shaanxi Province].

OBJECTIVE: To study the distributional characteristics of allergens in children with allergic diseases in Shaanxi province. METHODS: A total of 4 622 children diagnosed with allergic diseases in the Asthma Center, Department of Pediatrics, Xijing Hospital from March 2015 to February 2019 were selected. Serum allergen-specific immunoglobulin E (sIgE) of 19 common kinds of allergens were examined with enzyme-linked immunosorbent assay (ELISA). The children were divided into different groups according to sex, age and geographical regions, and the distributional characteristics of allergens of the different groups were compared. RESULTS: The overall positive rate for the 19 allergens of the 4 622 children was 62.8%. The ranking of the positive rates for individual allergens from high to low were as follows: 24.2% for milk, 18.0% for mold mix, 16.7% for dog dander, 16.4% for house dust mite, 11.7% for cat dander, 10.7% for cashew, 10.6% for weed pollen, 8.8% for egg white, 7.8% for house dust, 7.7% for tree pollen, 5.6% for amaranth, 4.9% for mulberry tree, 3.6% for mango, 3.2% for beef, 2.8% for cockroach, 2.1% for crab, 1.5% for shrimp, 0.8% for pineapple, and 0.3% for shellfish. Analysis based on sex showed that the allergen positive rates in boys were higher than those in girls. Analysis by age difference showed that generally the positive rates for inhaled allergens increased along with the increase in patient age, while the positive rates for ingested allergens decreased along with the increase in patient age. Analysis by geographical regions showed that the positive rate of house dust mite in the patients from the southern part of Shaanxi, the positive rate of weed pollen in the patients from the northern part of Shaanxi and the positive rates of milk and egg white in the patients from the central part of Shaanxi were higher than those in other areas. The cluster analysis and correlation analysis showed that the 19 allergens could be roughly divided into 4 categories. There were moderate correlations among tree pollen, mulberry tree and amaranth. There were moderate correlations among mulberry tree, mango and amaranth. There was moderate correlation between shrimp and crab, and there were mild or weak correlations among most of the other allergens. CONCLUSION: Among the 4 622 children with allergic diseases in Shaanxi Province who were treated in the Asthma Center, Department of Pediatrics, Xijing Hospital, male patients showed higher sensitivity to allergens. The positive rates of inhaled allergens increased, while the positive rates of ingested allergens decreased with increase in patient age. There were regional differences in the distribution of allergens. Some allergens were correlated with each other, which may be related to cross-reaction.