Bithiophene-Functionalized Infrared Two-Photon Absorption Metal Complexes as Single-Molecule Platforms for Synergistic Photodynamic, Photothermal, and Chemotherapy.

A planar conjugated ligand functionalized with bithiophene and its Ru(II), Os(II), and Ir(III) complexes have been constructed as single-molecule platform for synergistic photodynamic, photothermal, and chemotherapy. The complexes have significant two-photon absorption at 808 nm and remarkable singlet oxygen and superoxide anion production in aqueous solution and cells when exposed to 808 nm infrared irradiation. The most potent Ru(II) complex Ru7 enters tumor cells via the rare macropinocytosis, locates in both nuclei and mitochondria, and regulates DNA-related chemotherapeutic mechanisms intranuclearly including DNA topoisomerase and RNA polymerase inhibition and their synergistic effects with photoactivated apoptosis, ferroptosis and DNA cleavage. Ru7 exhibits high efficacy in vivo for malignant melanoma and cisplatin-resistant non-small cell lung cancer tumors, with a 100 % survival rate of mice, low toxicity to normal cells and low residual rate. Such an infrared two-photon activatable metal complex may contribute to a new generation of single-molecule-based integrated diagnosis and treatment platform to address drug resistance in clinical practice and phototherapy for large, deeply located solid tumors.

Bleeding the Excited State Energy to the Utmost: Single-Molecule Iridium Complexes for In Vivo Dual Photodynamic and Photothermal Therapy by an Infrared Low-Power Laser.

A series of cyclometalated Ir(III) complexes with morpholine and piperazine groups are designed as dual photosensitizers and photothermal agents for more efficient antitumor phototherapy via infrared low-power laser. Their ground and excited state properties, as well as the structural effect on their photophysical and biological properties, are investigated by spectroscopic, electrochemical, and quantum chemical theoretical calculations. They target mitochondria in human melanoma tumor cells and trigger apoptosis related to mitochondrial dysfunction upon irradiation. The Ir(III) complexes, particularly Ir6, demonstrate high phototherapy indexes to melanoma tumor cells and a manifest photothermal effect. Ir6, with minimal hepato-/nephrotoxicity in vitro, significantly inhibits the growth of melanoma tumors in vivo under 808 nm laser irradiation by dual photodynamic therapy and photothermal therapy and can be efficiently eliminated from the body. These results may contribute to the development of highly efficient phototherapeutic drugs for large, deeply buried solid tumors.

Molybdenum(V)-mediated switching of the C(sp2)-Se bond of phenylselenyl-functionalized arenes or heterocycles under mild conditions.

Molybdenum(V)-mediated cleavage of C(sp2)-Se bond and C(sp2)-H bond as well as intramolecular oxidative C(sp2)-Se coupling reaction of phenylselenyl-functionalized arenes or heterocycles has been developed. Three kinds of benzoselenophene frameworks were constructed through this reaction with yields up to 94%. This new C(sp2)-Se bond-switching methodology may provide a new strategy for interesting applications of phenylselenyl-substituted aromatic compounds in the synthesis of selenium-containing heterocycles and natural products.

Quantitative Evaluation of Chronic Obstructive Pulmonary Disease and Risk Prediction of Acute Exacerbation by High-Resolution Computed Tomography.

Objective: It is imperative to popularize the tertiary prevention of chronic obstructive pulmonary disease (COPD) and to improve the diagnosis and treatment. Methods: COPD patients were divided into mild (n = 18), moderate (n = 20), severe (n = 24), and extremely severe (n = 22) groups for performing high-resolution computed tomography (HRCT) and pulmonary function test. Serum procalcitonin (PCT) and high-sensitivity C-reactive protein (hs-CRP) were detected, and the occurrence rate of acute exacerbation COPD (AECOPD) was recorded during a 12-months follow-up period. Results: With an increase in the severity grade, the HRCT indexes, including emphysema index (EI), 1st and 15th percentile of inspiratory attenuation distribution (Perc1 and Perc15), ratio of expiratory/inspiratory mean lung density (MLDex/in) and lung volume (LVex/in), and ratio of the wall thickness to the outer diameter of the lumen (TDR), as well as percentage of the wall area to the total cross-sectional area (WA%) were increased with a decreased change in relative lung volume with attenuation values between -860 and -950 HU (RVC-860to -950) and lumen area (A i). These were correlated with the ratio of forced expiratory volume in 1 sec (FEV1) over forced vital capacity (FVC) (FEV1/FVC), the percentage of FEV1 the predicted value (FEV1%), and ratio of residual volume to total lung volume (RV/TLC). Body mass index, MLDex/in, FEV1%, FEV1/FVC, and PCT had a predictive value to AECOPD, with the combined AUC of 0.812. Conclusions: HRCT imaging effectively classifies the severity of COPD, which combined with BMI, PFT, and serum PCT can predict the risk of AECOPD.

Silver-catalysed three-component reactions of alkynyl aryl ketones, element selenium, and boronic acids leading to 3-organoselenylchromones.

An Ag-catalysed three-component reaction of alkynyl aryl ketones bearing an ortho-methoxy group, element selenium, and arylboronic acid, providing a facile route to selenofunctionalized chromone products has been developed. This protocol features high efficiency and high regioselectivity, and the use of selenium powder as the selenium source. Mechanistic experiments indicated that the combined oxidative effect of (bis(trifluoroacetoxy)iodo)benzene and oxygen in the air pushes the catalytic redox cycle of the Ag catalyst and the phenylselenium trifluoroacetate formed in situ is the key intermediate of the PIFA-mediated 6-endo-electrophilic cyclization and selenofunctionalization reaction of alkynyl aryl ketones.

Total synthesis of justicidin B, justicidin E, and taiwanin C: A general and flexible approach toward the synthesis of natural arylnaphthalene lactone lignans.

Lignans are widely present in traditional medicinal plants. Many natural arylnaphthalene lactone lignans (NALLs) isolated from the genera Justicia, Haplophyllum, and Phyllanthus possess interesting biological activities. Herein, we report a general strategy for the total synthesis of this kind of lignans. Features of this new approach are an aryl-alkyl Suzuki cross-coupling to introduce the dioxinone unit, a cation-induced cyclization to construct the aryl dihydronaphthalene, and base-mediated oxidative aromatization to furnish the arylnaphthalene core. By incorporating these key transformations, the total syntheses of justicidins B and E and taiwanin C covered type I and type II NALLs were accomplished.

Effect Observation on Modified Zishen Tongguan Decoction Combined with Acupuncture in Treatment of Urinary Retention after Cervical Cancer Surgery and Its Influence on the Incidence of Adverse Reactions.

OBJECTIVE: To explore the effect observation on modified Zishen Tongguan decoction combined with acupuncture in the treatment of urinary retention after cervical cancer surgery and its influence on the incidence of adverse reactions. METHODS: The clinical data of 84 patients suffered from urinary retention after radical resection of cervical cancer (December 2018-December 2019) in the oncology department of Jinan Municipal Hospital of Traditional Chinese Medicine were selected for retrospective analysis. According to the order of admission, they were divided into group A (n = 42), treated with conventional therapy, modified Zishen Tongguan decoction, and acupuncture, and group B (n = 42), treated with conventional therapy. The clinical efficacy of the two groups was observed, the urination function indexes after therapy were recorded, and the clinical efficacy and incidence of adverse reactions were analyzed. RESULTS: After therapy, compared with group B, the average urinary flow rate, maximum urinary flow rate, bladder compliance (BC) level value, and the number of patients with good recovery of bladder function of group A were obviously higher (P < 0.05), and the urination time and detrusor pressure were obviously lower (P < 0.001). There was no significant difference in the average scoring of overactive bladder syndrome score (OABSS) between the two groups at 7 days of therapy (p > 0.05). The average OABSS of group A at 14 days of therapy was obviously lower than that of group B (P < 0.001). Compared with group B, the total clinical effective rate of group A was obviously higher (P < 0.05), while the total incidence of adverse reactions was obviously lower (P < 0.05). CONCLUSION: Modified Zishen Tongguan decoction combined with acupuncture is a reliable method to treat urinary retention after cervical cancer surgery, which greatly improves the urination function of patients, as well as the clinical efficacy. Further research will help create a better solution for patients with urinary retention after cervical cancer surgery.

Discovery of potentially biased agonists of mu-opioid receptor (MOR) through molecular docking, pharmacophore modeling, and MD simulation.

Opioids are well known for their potent analgesic efficacy and severe side effects. Studies have shown that analgesic effects are mediated by the downstream G-protein-dependent pathway of the µ-opioid receptor (MOR), and another ß-arrestin-dependent pathway mediates side effects such as respiratory depression, constipation and tolerance etc. TRV130 is a biased ligand for G-protein-dependent pathway, which has high analgesia and has fewer side effects than morphine. In this study, the structure similarity search was performed on the IBSSC database using Oliceridine (TRV130) and PZM21 as templates. The 3D structure-based pharmacophore model was built and combined molecular docking prediction mode was selected to filter out small molecules, Finally, based on affinity prediction, four candidate molecules were obtained. Molecular dynamics simulations explored the detailed interaction mechanism of proteins with small molecules under dynamics. These results suggest that these candidate molecules are potential MOR agonists.

Synthesis, physicochemical properties, and health aspects of structured lipids: A review.

Structured lipids (SLs) refer to a new type of functional lipids obtained by chemically, enzymatically, or genetically modifying the composition and/or distribution of fatty acids in the glycerol backbone. Due to the unique physicochemical characteristics and health benefits of SLs (for example, calorie reduction, immune function improvement, and reduction in serum triacylglycerols), there is increasing interest in the research and application of novel SLs in the food industry. The chemical structures and molecular architectures of SLs define mainly their physicochemical properties and nutritional values, which are also affected by the processing conditions. In this regard, this holistic review provides coverage of the latest developments and applications of SLs in terms of synthesis strategies, physicochemical properties, health aspects, and potential food applications. Enzymatic synthesis of SLs particularly with immobilized lipases is presented with a short introduction to the genetic engineering approach. Some physical features such as solid fat content, crystallization and melting behavior, rheology and interfacial properties, as well as oxidative stability are discussed as influenced by chemical structures and processing conditions. Health-related considerations of SLs including their metabolic characteristics, biopolymer-based lipid digestion modulation, and oleogelation of liquid oils are also explored. Finally, potential food applications of SLs are shortly introduced. Major challenges and future trends in the industrial production of SLs, physicochemical properties, and digestion behavior of SLs in complex food systems, as well as further exploration of SL-based oleogels and their food application are also discussed.

Gastrodin Pretreatment Protects Liver Against Ischemia-Reperfusion Injury via Activation of the Nrf2/HO-1 Pathway.

Hepatic ischemia-reperfusion (IR) injury remains the major cause of liver damage post-liver surgery or transplantation. Diminishing oxidative stress and inflammatory responses is a powerful channel to reduce the rate of morbidity and mortality. Gastrodin (GSTD), a bioactive compound extracted from the traditional Chinese herbal agent with a long history of clinical application in nervous system diseases, is suggested to possess anti-oxidative effects on liver diseases, such as nonalcoholic fatty liver disease. However, the therapeutic potential of GSTD in liver IR injury remains unclear. In this paper, we performed surgery to set up the 70% hepatic IR injury models in mice after a three-day pretreatment of GSTD. We found the administration of GSTD reduced liver damage, which correlated with lower histological Suzuki's score, lower serum alanine transaminase (AST) and alanine transaminase (ALT) levels, less oxidative stress, and cell apoptosis in a dose-responsive manner, as compared to the parallel control. Meanwhile, we observed a great induction of heme oxygenase-1 (HO-1) and an activation of the p38 mitogen-activated protein kinases/nuclear factor erythroid 2-related factor 2 (p38MAPK/Nrf2) pathway in response to the GSTD pretreatment, while the protective effects upon GSTD diminished in mice with HO-1 heterozygous mutation. In addition, GSTD inhibited IR induced toll-like receptor (TLR) 4, but not TLR2 in a HO-1 dependent manner, leading to a down-regulation of cytokines, such as interleukin (IL)-6 and TNF-[Formula: see text]. Collectively, our findings revealed GSTD attenuated liver IR injury via activation of the HO-1 pathway, providing a novel therapeutic strategy to minimize the IR induced oxidative stress in the process of liver transplantation.

Analysis of the genes controlling three quantitative traits in three diverse plant species reveals the molecular basis of quantitative traits.

Most traits of agricultural importance are quantitative traits controlled by numerous genes. However, it remains unclear about the molecular mechanisms underpinning quantitative traits. Here, we report the molecular characteristics of the genes controlling three quantitative traits randomly selected from three diverse plant species, including ginsenoside biosynthesis in ginseng (Panax ginseng C.A. Meyer), fiber length in cotton (Gossypium hirsutum L. and G. barbadense L.) and grain yield in maize (Zea mays L.). We found that a vast majority of the genes controlling a quantitative trait were significantly more likely spliced into multiple transcripts while they expressed. Nevertheless, only one to four, but not all, of the transcripts spliced from each of the genes were significantly correlated with the phenotype of the trait. The genes controlling a quantitative trait were multiple times more likely to form a co-expression network than other genes expressed in an organ. The network varied substantially among genotypes of a species and was associated with their phenotypes. These findings indicate that the genes controlling a quantitative trait are more likely pleiotropic and functionally correlated, thus providing new insights into the molecular basis underpinning quantitative traits and knowledge necessary to develop technologies for efficient manipulation of quantitative traits.

Oxidation of dextran using H2O2 and NaClO/NaBr and their applicability in iron chelation.

The structural modification of polysaccharides directly affects their physicochemical properties and applications. Dextran, a chained polysaccharide, consists of multiple d-glucose molecules with repetitive structures. In this study, the physicochemical properties of oxidized dextran (DO) at different concentrations of NaClO/NaBr and H2O2 were compared. The results showed that NaClO/NaBr oxidation is more conducive to the formation of carboxyl groups. Oxidized dextran with NaClO/NaBr (DOB) showed good iron (III) chelating ability, and the DOB­iron (III) complex (DOBIC) had an iron content of 28.31%. According to structural analysis, NaClO/NaBr (2 g/100 g of active chlorine) and H2O2 (4 g/100 g), respectively, oxidize the C1 and C2 hydroxyl groups of dextran to carboxyl groups and open the ring when DO and iron have the strongest chelation ability. The complex is indeed a chelate iron complex, and iron core is composed of iron oxyhydroxide or the ß-FeOOH mineral polymorph. These results indicate that DOBIC is expected to be a good iron supplement or food additive to strengthen iron.

Exploring Aporphine as Anti-inflammatory and Analgesic Lead from Dactylicapnos scandens.

Dactylicapnosines A (1) and B (2), two reconstructed aporphines with unprecedent five-membered carbon ring D, were isolated from Dactylicapnos scandens, in which dactylicapnosine A showed potent anti-inflammatory bioactivity in vitro. Inspired by its biosynthetic pathway, the total synthesis of dactylicapnosine A via 10 steps has been achieved and afforded enough material to prove its significant anti-inflammatory effect in vivo.

Isoscoparins R and S, two new ent-clerodane diterpenoids from Isodon scoparius.

Two new ent-clerodane diterpenoids, named isoscoparins R and S (1 and 2), were isolated from the aerial parts of Isodon scoparius. Their structures were characterized mainly by analyzing the NMR and HRESIMS data, and the relative configuration of compound 1 was determined by single-crystal X-ray diffraction. Compound 2 showed weak activity as an autophagic inhibitor.

Gastrodin induced HO-1 and Nrf2 up-regulation to alleviate H2O2-induced oxidative stress in mouse liver sinusoidal endothelial cells through p38 MAPK phosphorylation.

Nuclear factor erythroid-related factor 2 (Nrf2) has been implicated in several detoxifying and antioxidant defense processes. Nrf2-mediated heme oxygenase-1 (HO-1) expression was demonstrated to play a key role against oxidative stress. Gastrodin (GSTD) is a well-known active compound isolated from the roots of Rhizoma gastrodiae, a plant used in ancient Chinese traditional medicine. The aim of this work was to investigate whether GSTD could alleviate H2O2-induced oxidative stress in mouse liver sinusoidal endothelial cells (LSECs). In LSECs exposed to 1 mM H2O2, treatment with GSTD (1, 10, or 50 µM) resulted in higher cell viability than the untreated control. Treated cells maintained a higher Bcl2/Bax ratio and suppressed caspase-9 expression compared with untreated cells, reducing cell apoptosis. GSTD was protective for H2O2-induced oxidative injury by reducing the generation of intracellular reactive oxygen species and malondialdehyde. HO-1 and Nrf2 expressions were synergistically upregulated by GSTD. Inhibition of HO-1 by 10 µM zinc protoporphyrin resulted in less protective effects on cell viability and malondialdehyde reduction by GSTD treatment in H2O2-exposed LSECs. Additionally, phosphorylated p38 in LSECs exposed to H2O2 was elevated by GSTD. Inhibition of p38 phosphorylation by SB203580 did not induce Nrf2 and HO-1 expression after 1 or 10 µM GSTD treatment and the protective effect on cell viability and malondialdehyde reduction in H2O2-exposed LSECs was reduced. The data conclusively demonstrated that GSTD-induced HO-1 and Nrf2 expression is involved in protection of LSECs from H2O2-induced oxidative injury, which may be regulated by p38 phosphorylation.

Scopariusols L-T, nine new ent-kaurane diterpenoids isolated from Isodon scoparius.

Nine new ent-kaurane diterpenoids, named scopariusols L-T (1-9), were isolated from the aerial parts of Isodon scoparius. Their structures were characterized mainly by analyzing the NMR and HR-ESI-MS data, and the absolute configuration of 1 was determined by single-crystal X-ray diffraction. Compound 1 was active against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW-480), and it also inhibited NO production in LPS-stimulated RAW264.7 cells, with an IC50 value of 0.6 µmol·L-1.

Gastrodin induced HO-1 and Nrf2 up-regulation to alleviate H2O2-induced oxidative stress in mouse liver sinusoidal endothelial cells through p38 MAPK phosphorylation

Nuclear factor erythroid-related factor 2 (Nrf2) has been implicated in several detoxifying and antioxidant defense processes. Nrf2-mediated heme oxygenase-1 (HO-1) expression was demonstrated to play a key role against oxidative stress. Gastrodin (GSTD) is a well-known active compound isolated from the roots of Rhizoma gastrodiae, a plant used in ancient Chinese traditional medicine. The aim of this work was to investigate whether GSTD could alleviate H2O2-induced oxidative stress in mouse liver sinusoidal endothelial cells (LSECs). In LSECs exposed to 1 mM H2O2, treatment with GSTD (1, 10, or 50 µM) resulted in higher cell viability than the untreated control. Treated cells maintained a higher Bcl2/Bax ratio and suppressed caspase-9 expression compared with untreated cells, reducing cell apoptosis. GSTD was protective for H2O2-induced oxidative injury by reducing the generation of intracellular reactive oxygen species and malondialdehyde. HO-1 and Nrf2 expressions were synergistically upregulated by GSTD. Inhibition of HO-1 by 10 µM zinc protoporphyrin resulted in less protective effects on cell viability and malondialdehyde reduction by GSTD treatment in H2O2-exposed LSECs. Additionally, phosphorylated p38 in LSECs exposed to H2O2 was elevated by GSTD. Inhibition of p38 phosphorylation by SB203580 did not induce Nrf2 and HO-1 expression after 1 or 10 µM GSTD treatment and the protective effect on cell viability and malondialdehyde reduction in H2O2-exposed LSECs was reduced. The data conclusively demonstrated that GSTD-induced HO-1 and Nrf2 expression is involved in protection of LSECs from H2O2-induced oxidative injury, which may be regulated by p38 phosphorylation.

New neo-clerodane diterpenoids with neurotrophic activity from the aerial parts of Salvia tiliifolia.

Five new neo-clerodane diterpenoids, tiliifolins A-E (1-5), along with ten known ones, were isolated from the aerial part of Salvia tiliifolia. Their structures were proposed based on 1D and 2D NMR spectroscopic data analysis. All new compounds were evaluated for their neurotrophic activity on PC12 cells and cytotoxicity against five human cancer cell lines (HL-60, A-549, SMMC-7721, MCF-7, and SW480), and compound 5 showed statistically significant neuroprotective effect in vitro assay.

Structurally Diverse Diterpenoids from Isodon scoparius and Their Bioactivity.

Fourteen new diterpenoids (1-14) based on four skeletal types and two known analogues (15 and 16) were isolated from the aerial parts of Isodon scoparius. Compound 2 is the first ent-kaurane diterpenoid featuring a 1,11-ether bridge, and the structures of these new compounds were established mainly by NMR and MS methods. The absolute configurations of 1 and 5 and the relative configuration of 3 were determined using single-crystal X-ray diffraction. The absolute configuration of 14 was determined by comparison of the experimental and calculated electronic circular dichroism spectra. Compounds 1, 4, and 15 were active against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW-480), and they also inhibited NO production in LPS-stimulated RAW264.7 cells, with IC50 values of 1.0, 3.1, and 1.8 µM, respectively.

Metabolic Effect of 1-Deoxynojirimycin from Mulberry Leaves on db/db Diabetic Mice Using Liquid Chromatography-Mass Spectrometry Based Metabolomics.

Metabolomics was applied to the liquid chromatography-mass spectrometry urinary metabolic profile of type 2 diabetes (T2DM) mice treated with mulberry 1-deoxynojirimycin (DNJ). The serum biochemical indicators related to T2DM like blood glucose, insulin, triglyceride, total cholesterol, nitrogen, malondialdehyde, and creatinine decreased significantly in the treated group. The histopathological changes in liver cells were marked by deformations and disruptions in central area of nuclei in DM mice, whereas DNJ treatment recovered regular liver cells with normal nuclei. Most of the metabolites of T2DM were significantly different from healthy controls in the bulk data generated. The level of 16 metabolites showed that the diabetic group was closer to the healthy group as the DNJ treatment time prolonged. Moreover, DNJ inhibited the activity of glucosidase on glucose, lipid, and amino acid metabolism. Our results showed the mechanism of DNJ treatment of T2DM and could fetch deep insights into the potent metabolite markers of the applied antidiabetic interventions.