Radical cascade silylation/cyclization of 1,7-dienes to access silyl-substituted benzo[b]azepin-2-ones.

A novel silyl radical-induced cascade silylation/cyclization of 1,7-dienes has been realized employing readily available hydrosilanes as a silicon source and Cu(I) salt as a catalyst. This protocol introduces diverse silicon fragments into a challenging 7-membered ring structure and provides an efficient approach to a wide array of biologically important silyl-substituted benzo[b]azepin-2-ones. Several control experiments suggest that the reaction undergoes a free radical process. The gram-scale synthesis and late-stage transformations further demonstrate the scalability and applicability of the reaction in organic synthesis.

Unsymmetrical Benzothieno-Fused BODIPYs as Efficient NIR Heavy-Atom-Free Photosensitizers.

Heavy-atom-free photosensitizers are potentially suitable for use in photodynamic therapy (PDT). In this contribution, a new family of unsymmetrical benzothieno-fused BODIPYs with reactive oxygen efficiency up to 50% in air-saturated toluene was reported. Their efficient intersystem crossing (ISC) resulted in the generation of both 1O2 and O2-• under irradiation. More importantly, the PDT efficacy of a respective 4-methoxystyryl-modified benzothieno-fused BODIPY in living cells exhibited an extremely high phototoxicity with an ultralow IC50 value of 2.78 nM. The results revealed that the incorporation of an electron-donating group at the α-position of the unsymmetrical benzothieno-fused BODIPY platform might be an effective approach for developing long-wavelength absorbing heavy-atom-free photosensitizers for precision cancer therapy.

Dynamically stable co-assembled supramolecular BOPPY systems with chiral amplification.

New and dynamical chiral co-assembled systems bearing BOPPY were successfully developed with amplified CPL signals. Remarkably, these stable chiral co-assemblies prepared at high concentrations retain uniform microrods and exceptional chiroptical performance (glum = 0.028, ΦF = 14%) after 48 h.

Synthesis, Properties, and Semiconducting Characteristics of Bisbenzothieno[b]-Fused BODIPYs.

A novel family of bisbenzothieno[b]-fused BODIPYs containing seven fused aromatic rings has been developed from readily available benzothieo[3,2-b]pyrroles through an efficient two-step synthetic route, exhibiting planar skeletons with excellent photostabilities, deep-red absorptions, and near-infrared emissions (up to 753 nm). Importantly, the thin-film transistors based on BTB with a meso-dimethylamino-phenyl group exhibit unipolar n-type charge transporting characteristics with a high electron mobility of 0.013 cm2 V-1 s-1.

Long-Wavelength Absorbing Benzimidazolo-Chlorin for Enhanced Photodynamic Therapy.

In this study, we condensed methyl pyropheophorbide-a (2) with 1,2-phenylenediamine to synthesize benzimidazolo-chlorin (3a) as an effective near-infrared photosensitizer (PS) with an absorption maximum of 730 nm. The ability of 3a to generate singlet oxygen, as well as its photodynamic effect on A549 and HeLa cells, was investigated. PS exhibited strong phototoxicity and negligible dark toxicity. Its structure was examined by UV-visible spectroscopy, nuclear magnetic resonance, and high-resolution fast atom bombardment mass spectrometry.

Examination of the negative correlation between leaf δ15N and the N:P ratio across a northeast-southwest transect in China.

Nitrogen (N) and phosphorus (P) are two crucial limiting mineral elements for terrestrial plants. Although the leaf N:P ratio is extensively used to indicate plant nutrient limitations, the critical N:P ratios cannot be universally applied. Some investigations have suggested that leaf nitrogen isotopes (δ15N) can provide another proxy for nutrient limitations along with the N:P ratio, but the negative relationships between N:P and δ15N were mainly limited to fertilization experiments. It will obviously benefit the study of the nature of nutrient limitations if the relationship could be explained more generally. We analyzed leaf δ15N, N, and P contents across a northeast-southwest transect in China. Leaf δ15N was weakly negatively correlated with leaf N:P ratios for all plants, while there was no correlation between them for various plant groups, including different growth forms, genera, and species across the entire N:P range. This suggests that the use of leaf δ15N in indicating the shift of nutrient limitations across the whole N:P range still requires more validated field investigations. Notably, negative relationships between δ15N and N:P hold for plants with N:P ratios between 10 and 20 but not for plants with N:P ratios lower than 10 or higher than 20. That is, changes in leaf δ15N along with the N:P ratio of plants that are co-limited by N and P can exhibit variations in plant nutrient limitations, whereas plants that are strictly limited by N and P cannot. Moreover, these relationships are not altered by vegetation type, soil type, MAP, or MAT, indicating that the use of leaf δ15N in reflecting shifts in nutrient limitations, depending on the plant nutrient limitation range, is general. We examined the relationships between leaf δ15N and the N:P ratio across an extensive transect, providing references for the widespread use of leaf δ15N in reflecting shifts in nutrient limitation.

Aromatic-Ring-Fused BOPPY Fluorophores: Synthesis, Spectral, Redox Properties, and Bioimaging Application.

Tetracoordinated organoboron dyes exhibiting strong fluorescence in either solution or the solid state are currently receiving much attraction in view of their photovoltaic, optoelectronic, and biological applications. Herein, a series of aromatic-ring-fused BOPPY dyes have been developed by one-pot condensation of formylated isoindoles or indoles and pyridinylhydrazine followed by subsequent borylation coordination. The facile synthesis provides excellent diversity of these unsymmetrical α-benzo- and ß-benzothiophene-fused BOPPY dyes with intriguing photophysical properties owing to their rigid and planar structure and extended π-conjugation while containing a reactive site. They display intense green to orange fluorescence in solution and red-to-near-infrared emission in the solid state, with high fluorescence quantum yields up to 92 and 21%, respectively, relatively large Stokes shifts, and excellent photostability. Furthermore, two representative benzo-fused BOPPY probes with morpholine or benzenesulfonamide groups were developed and used to selectively "light up" the subcellular organelles such as lysosomes and endoplasmic reticulum under ultralow concentration, respectively.

Different Lewis Acid Promotor-Steered Highly Regioselective Phosphorylation of Tertiary Enamides.

Different Lewis acid promotor-steered highly regioselective phosphorylation of tertiary enamides with diverse H-phosphonates or H-phosphine oxides was developed. Under the catalysis of iron salt, the phosphonyl group was introduced into the α-position of tertiary enamides, affording various α-phosphorylated amides in high efficiency. On the other hand, the ß-phosphorylated tertiary enamides were efficiently obtained as the products in the presence of manganese(III) acetylacetonate.

Preceding Phenological Events Rather than Climate Drive the Variations in Fruiting Phenology in the Desert Shrub Nitraria tangutorum.

Fruit setting and ripening are crucial in the reproductive cycle of many desert plant species, but their response to precipitation changes is still unclear. To clarify the response patterns, a long-term in situ water addition experiment with five treatments, namely natural precipitation (control) plus an extra 25%, 50%, 75%, and 100% of the local mean annual precipitation (145 mm), was conducted in a temperate desert in northwestern China. A whole series of fruiting events including the onset, peak, and end of fruit setting and the onset, peak, and end of fruit ripening of a locally dominant shrub, Nitraria tangutorum, were observed from 2012 to 2018. The results show that (1) water addition treatments had no significant effects on all six fruiting events in almost all years, and the occurrence time of almost all fruiting events remained relatively stable compared with leaf phenology and flowering phenology after the water addition treatments; (2) the occurrence times of all fruiting events were not correlated to the amounts of water added in the treatments; (3) there are significant inter-annual variations in each fruiting event. However, neither temperature nor precipitation play key roles, but the preceding flowering events drive their inter-annual variation.

K2S2O8/I2-Promoted Electrophilic Selenylative Cyclization To Access Seleno-Benzo[b]azepines.

A novel and simple organoselenium-involved 7-membered cyclization to access diverse seleno-benzo[b]azepines has been developed. This protocol involves an electrophilic cyclization process and is accomplished under mild conditions. Discussion of the mechanism rationalizes the regioselectivity observed in transformation. The studies of further transformation of seleno-benzo[b]azepines and large-scale experiment reveal the promising utility of this methodology.

Synthesis of Diverse Pentasubstituted Pyrroles by a Gold(I)-Catalyzed Cascade Rearrangement-Cyclization of Tertiary Enamide.

An efficient Au(I)-catalyzed intramolecular cascade reaction of tertiary enamides tethered an alkynyl group has been developed. The process is composed of a propargyl-claisen rearrangement and 5-exo-dig cyclization. This protocol provided a powerful method for the preparation of a variety of pentasubstituted pyrroles derivatives with excellent functional group tolerance in excellent yields. Scale-up experiment and chemical transformations of products exhibited the versatility of tertiary enamides in organic synthesis again.

Contrasting Regulators of the Onset and End of the Seed Release Phenology of a Temperate Desert Shrub Nitraria tangutorum.

Seed release is crucial in the reproductive cycle of many desert plant species, but their responses to precipitation changes are still unclear. To clarify the response patterns, we conducted a long-term in situ water addition experiment with five treatments, including natural precipitation (control) plus an extra 25%, 50%, 75%, and 100% of the local mean annual precipitation (145 mm), in a temperate desert in northwestern China. Both the onset and end of the seed release phenophase of the locally dominant shrub, Nitraria tangutorum, were observed from 2012 to 2018. The results showed that both the onset and end time of seed release, especially the end time, were significantly affected by water addition treatment. On average, the end time of seed release was advanced by 3.9 d, 7.3 d, 10.8 d, and 3.8 d under +25%, +50%, +75%, and +100% water addition treatments, respectively, over the seven-year study, compared with the control. The changes in the onset time were relatively small (only several hours), and the duration of seed release was shortened by 4.0 d, 7.5 d, 10.8 d, and 2.0 d under +25%, +50%, +75%, and +100% water addition treatments, respectively. The onset and end time of seed release varied greatly between the years. Preceding fruit ripening and summer temperature jointly regulated the inter-annual variation of the onset time of seed release, while the cumulative summer precipitation played a key role in driving the inter-annual variation of the end time. The annual mean temperature controlled the inter-annual variation of the seed release duration, and these interactions were all non-linear.

Diverse privileged N-polycyclic skeletons accessed from a metal-free cascade cyclization reaction.

An exquisite metal-free cascade cyclization reaction of 2-acylbenzoic acids with amines was developed, which provided a powerful method for the one-pot synthesis of diverse isoindoloisoquinoline and benzoindolizinoindole derivatives. This protocol avoided the use of metal catalysts, proceeded with high efficiency and had broad substrate scope. These resulting products could be transformed into tertiary amines under the reduction of LiAlH4/AlCl3, followed by the Hofmann elimination offering lots of nitrogen-containing nine-membered ring compounds in excellent yields. All synthesized products containing fused N-polycyclic skeletons were difficult to be constructed using traditional methods and they have a wide range of applications in the pharmaceutical area.

Effects of the Simulated Enhancement of Precipitation on the Phenology of Nitraria tangutorum under Extremely Dry and Wet Years.

Plant phenology is the most sensitive biological indicator that responds to climate change. Many climate models predict that extreme precipitation events will occur frequently in the arid areas of northwest China in the future, with an increase in the quantity and unpredictability of rain. Future changes in precipitation will inevitably have a profound impact on plant phenology in arid areas. A recent study has shown that after the simulated enhancement of precipitation, the end time of the leaf unfolding period of Nitraria tangutorum advanced, and the end time of leaf senescence was delayed. Under extreme climatic conditions, such as extremely dry or wet years, it is unclear whether the influence of the simulated enhancement of precipitation on the phenology of N. tangutorum remains stable. To solve this problem, this study systematically analyzed the effects of the simulated enhancement of precipitation on the start, end and duration of four phenological events of N. tangutorum, including leaf budding, leaf unfolding, leaf senescence and leaf fall under extremely dry and wet conditions. The aim of this study was to clarify the similarities and differences of the effects of the simulated enhancement of precipitation on the start, end and duration of each phenological period of N. tangutorum in an extremely dry and an extremely wet year to reveal the regulatory effect of extremely dry and excessive amounts of precipitation on the phenology of N. tangutorum. (1) After the simulated enhancement of precipitation, the start and end times of the spring phenology (leaf budding and leaf unfolding) of N. tangutorum advanced during an extremely dry and an extremely wet year, but the duration of phenology was shortened during an extremely wet year and prolonged during an extremely drought-stricken year. The amplitude of variation increased with the increase in simulated precipitation. (2) After the simulated enhancement of precipitation, the start and end times of the phenology (leaf senescence and leaf fall) of N. tangutorum during the autumn advanced in an extremely wet year but was delayed during an extremely dry year, and the duration of phenology was prolonged in both extremely dry and wet years. The amplitude of variation increased with the increase in simulated precipitation. (3) The regulation mechanism of extremely dry or wet years on the spring phenology of N. tangutorum lay in the different degree of influence on the start and end times of leaf budding and leaf unfolding. However, the regulation mechanism of extremely dry or wet years on the autumn phenology of N. tangutorum lay in different reasons. Water stress caused by excessive water forced N. tangutorum to start its leaf senescence early during an extremely wet year. In contrast, the alleviation of drought stress after watering during the senescence of N. tangutorum caused a delay in the autumn phenology during an extremely dry year.

Danshensu attenuates cisplatin-induced nephrotoxicity through activation of Nrf2 pathway and inhibition of NF-κB.

The clinical application of cisplatin was mainly limited by severe nephrotoxicity. Danshensu was the main pharmacological active diterpenoids which extracted from the roots of Salvia milthiorriza Bunge. This study is aimed to investigate the protective effects and potential mechanisms of Danshensu against cisplatin-induced nephrotoxicity. After fasting for 12 h, all mice groups except the control group were administered a single intraperitoneal injection of 25 mg/kg cisplatin. 1 h later, cisplatin (25 mg/kg) + Danshensu (15 mg/kg, 30 mg/kg, 60 mg/kg) groups were treated with corresponding doses of Danshensu once a day for 7 consecutive days. Blood urea nitrogen (BUN), creatinine, reactive oxygen species (ROS), superoxide dismutase (SOD), Glutathione peroxidase (GPx), Catalase (CAT) and malondialdehyde (MDA) were assayed in this study. The expression of inflammatory cytokines TNF-α, IL-6 and IL-1ß were examined by ELISA. The results showed that Danshensu could improve kidney damage, attenuate serum BUN, creatinine, cytokines and oxidative stress markers. Further studies showed that Danshensu can induce Nrf2/HO-1 activation and inhibition of NF-κB pathway. In conclusion, Danshensu exerts the protective effects on cisplatin-induced nephrotoxicity, which may be related to the activation of Nrf2/HO-1 and inhibition of NF-ĸB pathway.

Calycosin Induces Gastric Cancer Cell Apoptosis via the ROS-Mediated MAPK/STAT3/NF-κB Pathway.

BACKGROUND: Calycosin, an active compound in plants, can promote the apoptosis of various cancer cells; however, the mechanism by which it regulates reactive oxygen species (ROS) in gastric cancer (GC) cells remains unclear. PURPOSE: In this study, we investigated the effects of calycosin on apoptosis, the cell cycle, and migration in GC cells under ROS regulation. RESULTS: The results of the Cell Counting Kit-8 assay suggested that calycosin had significant cytotoxic effects on 12 gastric cancer cells, but no significant cytotoxic effects on normal cells. Hoechst 33342/propidium iodide (PI) double staining and flow cytometry showed that calycosin had clear pro-apoptotic effects on AGS cells. Western blotting revealed that the expression of cytochrome C and pro-apoptotic proteins B-cell lymphoma 2 (Bcl-2)-associated agonist of cell death (Bad), cleaved (cle)-caspase-3, and cle-poly (ADP-ribose) polymerase gradually increased, and the expression of anti-apoptotic protein Bcl-2 gradually decreased. Calycosin also decreased the expression of extracellular signal-regulated kinase, nuclear factor kappa B (NF-κB), and signal transducer and activator of transcription 3 (STAT3), and increased the phosphorylation levels of p38, c-Jun N-terminal kinase, and inhibitor of NF-κB. In addition, calycosin markedly increased ROS accumulation, and pretreatment with active oxygen scavenger n-acetyl-l-cysteine (NAC) clearly inhibited apoptosis. Calycosin downregulated the cell cycle proteins cyclin-dependent kinase 2 (CDK2), CDK4, CDK6, cyclin D1, and cyclin E; upregulated p21 and p27; and arrested cells in the G0/G1 phase. Similarly, calycosin also downregulated Snail family transcriptional repressor 1, E-cadherin, and ß-catenin and inhibited cell migration. However, pretreatment with NAC inhibited the calycosin-induced effects of cycle arrest and migration. CONCLUSION: In summary, calycosin induces apoptosis via ROS-mediated MAPK/STAT3/NF-κB pathways, thereby exerting its anti-carcinogenic functions in GC cells.

Synthetic methods for compounds containing fluoro-lactam units.

In recent years, considerable attention has been devoted to the exploration of novel synthetic methods for fluoro-lactams due to their significant biological and pharmaceutical activities. This review summarizes recently established strategies for synthesizing fluorine-substituted lactams, including fluoro-ß-lactams, fluoro-γ-lactams, and fluoro-δ-lactams. Additionally, the reaction scopes, limitations, and mechanisms are discussed.

Water Addition Prolonged the Length of the Growing Season of the Desert Shrub Nitraria tangutorum in a Temperate Desert.

Climate models often predict that more extreme precipitation events will occur in arid and semiarid regions, where plant phenology is particularly sensitive to precipitation changes. To understand how increases in precipitation affect plant phenology, this study conducted a manipulative field experiment in a desert ecosystem of northwest China. In this study, a long-term in situ water addition experiment was conducted in a temperate desert in northwestern China. The following five treatments were used: natural rain plus an additional 0, 25, 50, 75, and 100% of the local mean annual precipitation. A series of phenological events, including leaf unfolding (onset, 30%, 50%, and end of leaf unfolding), cessation of new branch elongation (30, 50, and 90%), and leaf coloration (80% of leaves turned yellow), of the locally dominant shrub Nitraria tangutorum were observed from 2012 to 2018. The results showed that on average, over the seven-year-study and in all treatments water addition treatments advanced the spring phenology (30% of leaf unfolding) by 1.29-3.00 days, but delayed the autumn phenology (80% of leaves turned yellow) by 1.18-11.82 days. Therefore, the length of the growing season was prolonged by 2.11-13.68 days, and autumn phenology contributed more than spring phenology. In addition, water addition treatments delayed the cessation of new branch elongation (90%) by 5.82-12.61 days, and nonlinear relationships were found between the leaves yellowing (80% of leaves) and the amount of watering. Linear relationships were found between the cessation of new branch elongation (90%), the length of the growing season, and amount of water addition. The two response patterns to water increase indicated that predictions of phenological events in the future should not be based on one trend only.

[Clinical efficacy of Matrine and Sodium Chloride Injection in treatment of 40 cases of COVID-19].

In this paper, we analyzed medical records of 40 patients with coronavirus disease 2019(COVID-19), in order to explore the clinical efficacy of Matrine and Sodium Chloride Injection in the treatment of COVID-19. The investigation was based on the results of a previous animal test, which was aimed to investigate and confirme the clinical efficacy of Matrine and Sodium Chloride Injection in the treatment of COVID-19. The animal test demonstrated that Matrine and Sodium Chloride Injection has a significant therapeutic effect on the human coronavirus pneumonia for the model mice. The lung inhibition index reached up to 86.86%. The evaluation was conducted on 40 confirmed cases of COVID-19 treated at Jingzhou Hospital of Infectious Disease(Chest Hospital) of Hubei Pro-vince from January 30~(th) to March 21~(th), 2020. In these cases, patients were treated with other integrated Chinese and Western medicines regimens in the recommended Matrine and Sodium Chloride Injection diagnosis and treatment regimen. The clinical manifestations, laboratory data, nucleic acid clearance time, and imaging data were compared and analyzed before and after treatment. After administration with Matrine and Sodium Chloride Injection, the clinical symptoms of 40 cases were alleviated markedly, and their blood analysis and biochemical indexes returned to normal. The lung CT showed more than 50% of lesion absorption rate, and the viral nucleic acid test showed the average clearance time of patients was 16.6 days, and the average length of hospital stay was 25.9 days. After administration with Matrine and Sodium Chloride Injection, the symptoms of cough and fatigue were alleviated significantly, and the appetite was significantly improved compared with before, especially for patients with gastrointestinal symptoms. Additionally, laboratory indicators, especially absolute value and ratio of lymphocytes and CRP were significantly alleviated. According to the chest CT for short-term review, the absorption of lung lesions was faster than before, especially for grid-like and fibrotic lesions. Compared with antiviral drugs, such as Abidol and Kriging, the nucleic acid clearance time was significantly shorter than the cases treated with Matrine and Sodium Chloride Injection. The clinical effective rate of 40 cases was 100.0%. We believed that Matrine and Sodium Chloride Injection have a good clinical effect in the treatment of COVID-19, and suggested increasing the clinical application and further conducting large-sample-size cli-nical verification.

Horizontal gene transfer of Fhb7 from fungus underlies Fusarium head blight resistance in wheat.

Fusarium head blight (FHB), a fungal disease caused by Fusarium species that produce food toxins, currently devastates wheat production worldwide, yet few resistance resources have been discovered in wheat germplasm. Here, we cloned the FHB resistance gene Fhb7 by assembling the genome of Thinopyrum elongatum, a species used in wheat distant hybridization breeding. Fhb7 encodes a glutathione S-transferase (GST) and confers broad resistance to Fusarium species by detoxifying trichothecenes through de-epoxidation. Fhb7 GST homologs are absent in plants, and our evidence supports that Th. elongatum has gained Fhb7 through horizontal gene transfer (HGT) from an endophytic Epichloë species. Fhb7 introgressions in wheat confers resistance to both FHB and crown rot in diverse wheat backgrounds without yield penalty, providing a solution for Fusarium resistance breeding.