A Distinctive Insight into Inorganic Sonosensitizers: Design Principles and Application Domains.

Sonodynamic therapy (SDT) as a promising non-invasive anti-tumor means features the preferable penetration depth, which nevertheless, usually can't work without sonosensitizers. Sonosensitizers produce reactive oxygen species (ROS) in the presence of ultrasound to directly kill tumor cells, and concurrently activate anti-tumor immunity especially after integration with tumor microenvironment (TME)-engineered nanobiotechnologies and combined therapy. Current sonosensitizers are classified into organic and inorganic ones, and current most reviews only cover organic sonosensitizers and highlighted their anti-tumor applications. However, there have few specific reviews that focus on inorganic sonosensitizers including their design principles, microenvironment regulation, etc. In this review, inorganic sonosensitizers are first classified according to their design rationales rather than composition, and the action rationales and underlying chemistry features are highlighted. Afterward, what and how TME is regulated based on the inorganic sonosensitizers-based SDT nanoplatform with an emphasis on the TME targets-engineered nanobiotechnologies are elucidated. Additionally, the combined therapy and their applications in non-cancer diseases are also outlined. Finally, the setbacks and challenges, and proposed the potential solutions and future directions is pointed out. This review provides a comprehensive and detailed horizon on inorganic sonosensitizers, and will arouse more attentions on SDT.

Regulation of Released Alkali from Gel Polymer Electrolyte in Quasi-Solid State Zn-Air Battery.

Gel polymer electrolyte (GPE) in quasi-solid state Zn-air battery (QSZAB) will release alkali during cycling, resulting in gradual dehydration of GPE, corrosion of Zn electrode, Zn dendrites growth, and therefore inferior performance. Here, hollow Sn microspheres are prepared on Zn substrate by the technique of colloidal self-assembly. The inner surfaces of hollow Sn microspheres are modified by 2-hydroxypropyl-ß-cyclodextrin (hollow Sn-inner HPßCD) to regulate the released alkali at GPE|anode interface. The hollow Sn-inner HPßCD can lessen the leakage of released alkali, make stored alkali diffuse back to GPE during the charging process, and mitigate the loss of soluble Zn(OH)4 2- to suppress Zn dendrites growth. Resultantly, GPE in QSZAB with hollow Sn-inner HPßCD exhibits a high retention capacity for alkaline solution. The cell also exhibits a long cyclic lifespan of 127 h due to the effective regulation of released alkali, which outperforms QSZAB without hollow Sn-inner HPßCD by 7.94 times. This work rivets the regulation of released alkali at GPE|anode interface, providing new insight to improve QSZABs' performance.

AgSbF6-catalyzed C3 aza-Friedel-Crafts alkylation of N,O-acetals with indoles for the synthesis of N-α indole substituted pyrrolidine and piperidine derivatives.

An efficient approach to access chiral N-α indole substituted pyrrolidine and piperidine skeletons has been developed through a AgSbF6-catalyzed N-α aza-Friedel-Crafts alkylation of N,O-acetals 6a, 6b, 9, and 11a-11d with indoles. As a result, a series of 2,3-trans N-α indole substituted pyrrolidines 8a-8x and piperidines 10a-10j were prepared in moderate to excellent yields and with excellent diastereoselectivities (dr up to 99 : 1). Moreover, several 2,5-cis-N-α indole substituted pyrrolidine derivatives 12a-12k were synthesized according to this strategy with moderate to good yields and diastereoselectivities (dr up to 99 : 1).

Xanthones with Potential Anti-Inflammatory and Anti-HIV Effects from the Stems and Leaves of Cratoxylum cochinchinense.

Four new xanthones, cratocochinones A-D (1-4), together with eight known analogues (5-12), were isolated from the stems and leaves of Cratoxylum cochinchinense. The chemical structures of cratocochinones A-D (1-4) were elucidated by comprehensive spectroscopic analyses and the known compounds were identified by comparisons with the spectral data reported in the literature. All isolated compounds 1-12 were evaluated for their anti-inflammatory activities and anti-HIV-1 activities. Compounds 1-12 showed remarkable inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro, with IC50 values in the range of 0.86 ± 0.05 to 18.36 ± 0.21 µM. Meanwhile, compounds 1-12 exhibited significant anti-HIV-1 activities with EC50 which ranged from 0.22 to 11.23 µM. These findings indicate that the discoveries of these xanthones, isolated from the stems and leaves of C. cochinchinense, showing significant anti-inflammatory and anti-HIV-1 effects could be of great importance to the research and development of new natural anti-inflammatory and anti-HIV agents.

Palladium-Catalyzed Sequential Heck Reactions of Olefin-Tethered Aryl Iodides with Alkenes.

An efficient approach to functionalized (E)-3-cinnamyl-3-methyl-2,3-dihydrobenzofurans and (E)-(3-methyl-2,3-dihydrobenzofuran-3-yl)but-2-enones has been developed through a Pd-catalyzed one-pot cascade process involving two sequential Heck reactions, that is, an intramolecular Heck reaction of olefin-tethered aryl iodides and an intermolecular Heck reaction with substituted styrenes and α,ß-unsaturated ketones. As a result, a series of desired products were obtained in moderate to good yields and with exclusive E-form selectivities.

AgNTf2-Catalyzed Regioselective C-H Alkenylation of N,N-Dialkylanilines with Ynamides.

Regioselective C-H alkenylation of N,N-dialkylanilines with ynamides was developed using AgNTf2 as a catalyst. This approach represents a facile hydroarylation of ynamides, allowing for the introduction of an alkenyl group exclusively at the para position of aniline derivatives. As a result, a series of 4-alkenyl N,N-dialkylanilines were synthesized with excellent regioselectivities.

AgNTf2 catalyzed cycloaddition of N-acyliminium ions with alkynes for the synthesis of the 3,4-dihydro-1,3-oxazin-2-one skeleton.

A catalyzed process for the synthesis of the 4,6-substituted 3,4-dihydro-1,3-oxazin-2-one skeleton has been developed through cycloaddition of in situ generated acyliminium intermediates with alkynes. A range of chain N,O-acetals and terminal alkynes were amenable for this mild transformation. As a result, a series of desired cycloaddition products were obtained in moderate to good yields.

The Physiology of Postharvest Tea (Camellia sinensis) Leaves, According to Metabolic Phenotypes and Gene Expression Analysis.

Proper postharvest storage preserves horticultural products, including tea, until they can be processed. However, few studies have focused on the physiology of ripening and senescence during postharvest storage, which affects the flavor and quality of tea. In this study, physiological and biochemical indexes of the leaves of tea cultivar 'Yinghong 9' preserved at a low temperature and high relative humidity (15-18 °C and 85-95%, PTL) were compared to those of leaves stored at ambient conditions (24 ± 2 °C and relative humidity of 65% ± 5%, UTL). Water content, chromatism, chlorophyll fluorescence, and key metabolites (caffeine, theanine, and catechins) were analyzed over a period of 24 h, and volatilized compounds were determined after 24 h. In addition, the expression of key biosynthesis genes for catechin, caffeine, theanine, and terpene were quantified. The results showed that water content, chromatism, and chlorophyll fluorescence of preserved leaves were more similar to fresh tea leaves than unpreserved tea leaves. After 24 h, the content of aroma volatiles and caffeine significantly increased, while theanine decreased in both groups. Multiple catechin monomers showed distinct changes within 24 h, and EGCG was significantly higher in preserved tea. The expression levels of CsFAS and CsTSI were consistent with the content of farnesene and theanine, respectively, but TCS1 and TCS2 expression did not correlate with caffeine content. Principal component analysis considered results from multiple indexes and suggested that the freshness of PTL was superior to that of UTL. Taken together, preservation conditions in postharvest storage caused a series of physiological and metabolic variations of tea leaves, which were different from those of unpreserved tea leaves. Comprehensive evaluation showed that the preservation conditions used in this study were effective at maintaining the freshness of tea leaves for 2-6 h. This study illustrates the metabolic changes that occur in postharvest tea leaves, which will provide a foundation for improvements to postharvest practices for tea leaves.

[Quality evaluation of Psoraleae Fructus based on QAMS method and TLC identification].

The present study established a determination method of Psoraleae Fructus by quantitative analysis of multi-components by the single marker(QAMS) and further improved the thin-layer chromatography(TLC) method. The QAMS method was established by UPLC with psoralen as the internal marker, and the content of psoralenoside, isopsoralenoside, psoralen, and isopsoralen was simultaneously determined. As revealed by the comparison with results of the external standard method, the QAMS method was accurate and feasible. According to the current quality standards of Psoraleae Fructus, the TLC method was further optimized and improved, and bakuchiol was added for identification based on the original TLC method with psoralen and isopsoralen as indicators. This study provides a reference for improving the quality control method of Psoraleae Fructus.

Nanofiber Composite for Improved Water Retention and Dendrites Suppression in Flexible Zinc-Air Batteries.

Water loss of the gel polymer electrolytes (GPEs) and dendrites growth on Zn anode are overriding obstacles to applying flexible zinc-air batteries (ZABs) for wearable electronic devices. Nearly all previous efforts aim at developing novel GPEs with enhanced water retention and therefore elongate their lifespan. Herein, a facile interface engineering strategy is proposed to retard the water loss of GPE from the half-open structured air cathode. In detail, the poly(ethylene vinyl acetate)/carbon powder (PEVA-C) nanofiber composite interface layer with features of hydrophobicity, high conductivity, air permeability, and flexibility are prepared on the carbon cloth and set up between the GPE and electrode. The as-assembled ZAB with simple alkaline PVA GPE exhibits an impressive cycle life of 230 h, which outperforms ZAB without the PEVA-C nanofibers interface layer by 14 times. Additionally, the growth of Zn dendrites can be suppressed due to the tardy water loss of GPE.

A One-Pot Approach to 2-Substituted-2-(Dimethoxyphosphoryl)-Pyrrolidines from Substituted tert-Butyl 4-Oxobutylcarbamates and Trimethyl Phosphite.

A novel approach to 2-substituted-2-(dimethoxyphosphoryl)-pyrrolidines 7a-7o and 9a-9r has been developed, which features a TMSOTf-mediated one-pot intramolecular cyclization and phosphonylation of substituted tert-butyl 4-oxobutylcarbamates. The major advantages of this method include simple operation under mild reaction conditions, the use of cheap Lewis acid, and good to excellent yields with high diastereoselectivities (dr up to 99:1).

Asymmetric Synthesis of Spiropyrazolones via Chiral Pd(0)/Ligand Complex-Catalyzed Formal [4+2] Cycloaddition of Vinyl Benzoxazinanones with Alkylidene Pyrazolones.

In the presence of the chiral Pd(0)/ligand complex, vinyl benzoxazinanones underwent the [4+2] cycloaddition with alkylidene pyrazolones smoothly and delivered spiropyrazolones in reasonable yields, diastereoselectivities, and eneantioselectivities (up to >99% yield, >99:1 dr and 99% ee). The absolute configuration of the obtained spiropyrazolones was unambiguously characterized with the use of X-ray single-crystal structure analysis. Moreover, the reaction mechanism was assumed to interpret the formation of the target compounds.

Clausanisumine, a Prenylated Bicarbazole Alkaloid from the Fruits of Clausena anisum-olens and Its Potential Anti-HIV Activity.

A unique prenylated bicarbazole alkaloid, clausanisumine (1), and two biogenetically related known monomer carbazole alkaloids, mukonal (2) and 3-methylcarbazole (3), were isolated from the fruits of Clausena anisum-olens. Clausanisumine (1) was an uncommon prenylated bicarbazole alkaloid, possessing an unprecedented carbon skeleton, which was composed of a simple carbazole alkaloid and a prenylated carbazole alkaloid. The chemical structure of 1 was established by a combination of comprehensive spectral methods. A plausible biosynthetic pathway of 1 was also proposed. Additionally, the potential anti-HIV activities of all isolates 1-3 in vitro were evaluated. Compound 1 exhibited remarkable anti-HIV-1 reverse transcriptase effects showing an EC50 value of 18.58 nM. The discovery of the prenylated bicarbazole alkaloid from C. anisum-olens with notable anti-HIV activity would be meaningful to discovering and developing new anti-HIV drugs.

Carbazole alkaloids from the fruits of Clausena anisum-olens with potential PTP1B and α-glucosidase inhibitory activities.

The phytochemical investigation on the fruits of Clausena anisum-olens led to the isolation of 18 carbazole alkaloids (1-18), containing three new ones, clausenanisines A-C (1-3), and three new naturally occurring carbazole alkaloids, clausenanisines D-F (4-6), as well as 12 known analogues (7-18). The chemical structures of clausenanisines A-F (1-6) were elucidated by extensive spectroscopic methods. Notably, clausenanisine A (1) was a novel carbazole alkaloid with a unique five-membered cyclic ether, while clausenanisine E (5) is an unusual carbazole alkaloid owning an unprecedented naturally occurring carbon skeleton possessing 14 carbon atoms. The known carbazole alkaloids (7-18) were identified by the comparison of their spectral data with those data reported in the literature. All known carbazole alkaloids 7-18 were isolated from C. anisum-olens for the first time. Moreover, all isolated compounds 1-18 were assessed for their protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase inhibitory activities in vitro. Compounds 1-18 exhibited remarkable PTP1B inhibitory activities with IC50 values in the range of 0.58 ± 0.05 to 38.48 ± 0.32 µM, meanwhile, compounds 1-18 displayed significant α-glucosidase inhibitory activities with IC50 values ranging from 3.28 ± 0.16 to 192.23 ± 0.78 µM. These research results imply that the separation and identification of these carbazole alkaloids showing notable PTP1B and α-glucosidase inhibitory activities from the fruits of C. anisum-olens can be very significant for discovering and developing new PTP1B inhibitors and α-glucosidase inhibitors for the treatment of diabetes mellitus.

Process optimization to enhance utilization efficiency of precipitants for chloride removal from flue gas desulfurization wastewater via Friedel's salt precipitation.

The treatment cost for Cl- removal by Friedel's salt precipitation depended significantly on utilization rate of the precipitant aluminate. In this study, effects of Ca/Al molar ratio, reaction time, temperature and Al/Cl molar ratio were investigated to maximize Al utilization rate for Cl- removal from flue gas desulfurization wastewater. Batch results showed that the maximum Al utilization rate of 55.8-60.3% was obtained at Ca/Al ratio of 3.00, reaction time of 90 min, temperature of 35 °C and Al/Cl ratio of 0.50 regardless of the initial Cl- concentration. The precipitate obtained at the highest Al utilization rate had the highest interlayer spacing, the best crystal integrity, and the strongest binding energy of the Al-OH bond. The optimized condition made ion exchange between Cl- and OH- easier, and obtained more stable Friedel's salt structure to adsorb Cl-. Pilot-scale results showed that maximizing Al utilization rate with low dosages of precipitants had insignificant effects on the removal of Mg2+, Ca2+ and sulfate compared to the strategy to maximize Cl-, but enhanced Al utilization rate from 38.2% to 56.4%. Economic analysis showed that enhancing Al utilization rate greatly reduced treatment cost of the Friedel's salt precipitation method by 30.5%, and made the two-stage desalination process more feasible and worth popularizing.

[Chemical constituents from Clausena excavata and their inhibitory activities against proliferation of synoviocytes].

The chemical constituents from the stems and leaves of Clausena excavata were isolated and purified by column chromatography with silica gel, ODS, Sephadex LH-20 and RP-HPLC. The chemical structures of the isolated compounds were identified on the basis of physicochemical properties, spectroscopic analysis, as well as the comparisons with the data reported in literature. Nineteen compounds were isolated from the 90% ethanol extract of the stems and leaves of C. excavata, which were identified as methyl orsellinate(1), syringaresinol(2), lenisin A(3), scopoletin(4), osthenol(5), N-benzoyltyrarnine methyl ether(6), N-p-coumaroyltyramine(7), aurantiamide acetate(8), 1H-indole-3-carboxaldehyde(9), furostifoline(10), clausenalansine E(11), 3-formylcarbazole(12), clausine L(13), clausine E(14), methyl carbazole-3-carboxylate(15), glycosinin(16), murrayafoline A(17), clausine H(18) and 2,7-dihydroxy-3-formyl-1-(3'-methyl-2'-butenyl)carbazole(19). Among these isolated compounds, compounds 1-11 were isolated from C. excavata for the first time, and compounds 1, 2 and 10 were isolated from the genus Clausena for the first time. In addition, this study evaluated the anti-rheumatoid arthritis activities of compounds 1-19 by measuring their anti-proliferative effects on synoviocytes in vitro according to MTS method. Compounds 10-19 displayed remarkable anti-rheumatoid arthritis activities, which exhibited the inhibitory effects on the proliferation of MH7 A synovial fibroblast cells with the IC_(50) values ranging from(27.63±0.18) to(235.67±2.16) µmol·L~(-1).

Structural characterization, antiproliferative and anti-inflammatory activities of alkaloids from the roots of Zanthoxylum austrosinense.

Three new carbazole alkaloids, zanthoaustrones A-C (1-3), as well as nine known compounds 4-12, were isolated and characterized from the roots of Zanthoxylum austrosinense Huang (Rutaceae). Their chemical structures were elucidated on the basis of extensive and comprehensive spectroscopic methods, while the known alkaloids were identified by the comparison of their observed spectroscopic data including NMR data, MS data and optical rotation values with the data described in the literature. Furthermore, the antiproliferative activities as well as the anti-inflammatory effects of all isolated alkaloids in vitro were evaluated. All obtained alkaloids 1-12 displayed notable antiproliferative activities against diverse human cancer cell lines exhibiting IC50 values in range of 0.85 ± 0.06 to 29.56 ± 0.17 µM, which is equivalent to the positive control (cisplatin) showing IC50 values ranging from 1.58 ± 0.09 to 28.69 ± 0.21 µM. Moreover, compounds 1-12 exhibited pronounced inhibitory activities on nitric oxide (NO) production with IC50 values displaying IC50 values in range of 0.89 ± 0.05 to 9.62 ± 0.15 µM, which is comparable to the positive control (hydrocortisone) holding an IC50 value of 4.06 ± 0.11 µM. These findings indicate that the separation and characterization of these alkaloids displaying significant antiproliferative activities together with anti-inflammatory effects from the roots of Z. austrosinense could be meaningful to the research and development of new anti-cancer drugs as well as anti-inflammatory agents.

PIDD mediates the association of DNA-PKcs and ATR at stalled replication forks to facilitate the ATR signaling pathway.

The DNA-dependent protein kinase (DNA-PK), consisting of the DNA binding Ku70/80 heterodimer and the catalytic subunit DNA-PKcs, has been well characterized in the non-homologous end-joining mechanism for DNA double strand break (DSB) repair and radiation resistance. Besides playing a role in DSB repair, DNA-PKcs is required for the cellular response to replication stress and participates in the ATR-Chk1 signaling pathway. However, the mechanism through which DNA-PKcs is recruited to stalled replication forks is still unclear. Here, we report that the apoptosis mediator p53-induced protein with a death domain (PIDD) is required to promote DNA-PKcs activity in response to replication stress. PIDD is known to interact with PCNA upon UV-induced replication stress. Our results demonstrate that PIDD is required to recruit DNA-PKcs to stalled replication forks through direct binding to DNA-PKcs at the N' terminal region. Disruption of the interaction between DNA-PKcs and PIDD not only compromises the ATR association and regulation of DNA-PKcs, but also the ATR signaling pathway, intra-S-phase checkpoint and cellular resistance to replication stress. Taken together, our results indicate that PIDD, but not the Ku heterodimer, mediates the DNA-PKcs activity at stalled replication forks and facilitates the ATR signaling pathway in the cellular response to replication stress.

Geranylated carbazole alkaloids with potential neuroprotective activities from the stems and leaves of Clausena lansium.

Clausena lansium (Lour.) Skeels is an evergreen small tree or shrub with great economic value, which belongs to the genus Clausena of the Rutaceae family. C. lansium is indigenous to Southern China, while currently widely cultivated in subtropical and tropical regions not only for the nutritional value and pharmacological uses of its fruits but also as a medicinal and ornamental plant. In this study, a systematic phytochemical study on the stems and leaves of C. lansium caused the separation and identification of two new geranylated carbazole alkaloids, clauselansiumines A (1) and B (2), as well as 10 known geranylated carbazole alkaloids (3-12). The chemical structures of these isolated geranylated carbazole alkaloids (1-12) were unambiguously determined based on comprehensive spectral data analyses. All these isolated geranylated carbazole alkaloids were tested for their neuroprotective effects against 6-hydroxydopamine induced cell death in human neuroblastoma SH-SY5Y cells in vitro. Compounds 1-12 displayed remarkable neuroprotective effects holding the EC50 values ranging from 0.48 ±â€¯0.04 to 12.36 ±â€¯0.16 µM. These research results disclosed that the separation and purification of these geranylated carbazole alkaloids possessing remarkable neuroprotective effects separated from C. lansium could be extremely important to the discovery of new agents for the treatment and prevention for Parkinson's disease.

[Chemical constituents from stems and leaves of Clausena emarginata].

The chemical constituents from the stems and leaves of Clausena emarginata were separated and purified by column chromatographies on silica gel,ODS,Sephadex LH-20,and PR-HPLC. The structures of the isolated compounds were identified on the basis of physicochemical properties and spectroscopic analysis,as well as comparisons with the data reported in the literature. Sixteen compounds were isolated from the 90% ethanol extract of the stems and leaves of C. emarginata,which were identified as siamenol( 1),murrastanine A( 2),3-formyl-1,6-dimethoxycarbazole( 3),3-methoxymethylcarbazole( 4),3-methylcarbazole( 5),murrayafoline A( 6),3-formylcarbazole( 7),3-formyl-1-hydroxycarbazole( 8),3-formyl-6-methoxycarbazole( 9),murrayanine( 10),murrayacine( 11),girinimbine( 12),nordentatin( 13),chalepin( 14),8-hydroxy-6-methoxy-3-pentylisocoumarin( 15) and ethyl orsellinate( 16). Compounds 1-4,14-16 were isolated from C. emarginata for the first time. Among them,compounds 1,2,15 and 16 were isolated from the genus Clausena for the first time. All isolated compounds were evaluated for their cytotoxic activities against five human cancer cell lines: HL-60,SMMC-7721,A-549,MCF-7 and SW480 in vitro. Compounds 12 and 14 showed significant inhibitory effects against various human cancer cell lines with IC_(50) values comparable to those of doxorubicin.