A Functional Electrolyte Containing P-Phenyl Diisothiocyanate (PDITC) Additive Achieves the Interphase Stability of High Nickel Cathode in a Wide Temperature Range.

The lithium-ion batteries (LIBs) with high nickel cathode have high specific energy, but as the nickel content in the cathode active material increases, batteries are suffering from temperature limitations, unstable performance, and transition metal dissolution during long cycling. In this work, a functional electrolyte with P-phenyl diisothiocyanate (PDITC) additive is developed to stabilize the performance of LiNi0.8 Co0.1 Mn0.1 O2 (NCM811)/graphite LIBs over a wide temperature range. Compared to the batteries without the additive, the capacity retention of the batteries with PDITC-containing electrolyte increases from 23 % to 74 % after 1400 cycles at 25 °C, and from 15 % to 85 % after 300 cycles at 45 °C. After being stored at 60 °C, the capacity retention rate and capacity recovery rate of the battery are also improved. In addition, the PDITC-containing battery has a higher discharge capacity at -20 °C, and the capacity retention rate increases from 79 % to 90 % after 500 cycles at 0 °C. Both theoretical calculations and spectroscopic results demonstrate that PDITC is involved in constructing a dense interphase, inhibiting the decomposition of the electrolyte and reducing the interfacial impedance. The application of PDITC provides a new strategy to improve the wide-temperature performance of the NCM811/graphite LIBs.

1,2,3,4-Tetrakis(2-cyanoethoxy)butane (TCEB)-Assisted Construction of Self-Repair Electrode Interface Films to Improve the Performance of 4.5 V Pouch LiCoO2/Artificial Graphite Full Cells Operating at 45 °C.

1,2,3,4-Tetrakis(2-cyanoethoxy)butane (TCEB) is first evaluated as a functional electrolyte additive to increase the charge cutoff voltage and energy density of pouch LiCO2 (LCO)/artificial graphite (AG) lithium-ion batteries (LIBs) at a high temperature of 45 °C. The charge (0.7 C) and discharge (1 C) tests show that TCEB effectively improves the cycle stability of cells under a high charge cutoff voltage of 4.5 V. At 25 °C, the capacity retention of the cells with TCEB increases from 0.0% to 72.1% after 1200 cycles. At 45 °C, the capacity retention of the cells without TCEB after 50 cycles is close to 0.0%, while the capacity retention of the cells with TCEB is still 81.6%, even after 350 cycles. The spectroscopic characterization results demonstrate that the TCEB electrolyte additive participates in the construction of a self-repair electrode/electrolyte interface film. Subsequently, low impedance and strong protective layers are formed on the two electrode surfaces. The quantitative analysis results and a theoretical calculation also show that TCEB effectively inhibits the dissolution of Co3+ and maintains the structural integrity of electrode materials. These results indicate that TCEB endows LIBs with excellent cycle stability and is a promising electrolyte additive for the high-voltage and high-temperature conditions of LCO-based LIBs.

Design, synthesis, and evaluation of proliferation inhibitory activity of novel L-shaped ortho-quinone analogs as anticancer agents.

In this study, we present the design and synthesis of novel fully synthetic L-shaped ortho-quinone analogs with tanshinone IIA as the lead compoud, which is a molecule with numerous pharmacological benefits and potential to treat life-threatening diseases, such as cancer and viral infections. 24 L-shaped ortho-quinone analogs were designed and synthesized via click chemistry and introduced 1,2,3-triazole at the C-2 terminal of the furan ring. The cytotoxicity of these analogs toward different cancer cell lines was investigated in vitro. The new TD compounds showed potent inhibitory activities toward prostate cancer (PC3), leukemia (K562), breast cancer (MDA-231), lung cancer (A549), and cervical cancer (Hela) cell lines. Among them, TD1, TD11, and TD17 showed excellent broad-spectrum cytotoxic effects on five cancer cell lines by inducing apoptosis and arresting the cell cycle phase. Besides, TD1, TD11, and TD17 could target-bind with NQO1 protein in the prostate cancer cells PC3 leukemia cells K562. The results showed that removing the methyl group at C-3 and introducing 1,2,3-triazoles at the C-2 terminal of the furan ring were effective strategies for improving the broad-spectrum anticancer activity of L-shaped ortho-quinone analogs.

Ultrasmall MoS2 nanodots-wrapped perfluorohexane nanodroplets for dual-modal imaging and enhanced photothermal therapy.

Development of a multifunctional nanotherapeutic agent with high contrast-enhanced dual-modal imaging and photothermal therapy (PTT) efficacy is of great interest. Combination of ultrasound (US) and computed tomography (CT) imaging offers high spatial resolution images, showing great potential in medical imaging. Herein, the semiconducting perfluorohexane (PFH) nanodroplets, MoS2-PFH-PLLAs, are developed by stabilizing PFH droplets with the coating shell of poly (lactic-co-glycolic acid) (PLLA) and encapsulating the droplets with photoabsorbers of ultrasmall molybdenum disulfide (MoS2) nanodots. Upon near-infrared (NIR) irradiation, the MoS2-PFH-PLLAs can absorb the NIR light and convert it into heat, which not only promotes liquid-to-gas phase transition of PFH but also triggers photothermal heating, resulting in contrast-enhanced US/CT imaging and photothermal killing effect in vitro. Furthermore, the production of microbubbles can serve as the blasting agents to collaboratively enhance PTT efficacy after NIR irradiation. When intravenously injected into tumor-bearing mice, the MoS2-PFH-PLLAs exhibit a dual-modal US/CT imaging-guided synergistically therapeutic efficacy under NIR irradiation, resulting in tumor ablation. These nanotherapeutic agents demonstrate good biocompatibility, highly contrast-enhanced US/CT imaging, and combinational enhanced PTT efficacy.

Potent Cytotoxicity of Novel L-Shaped Ortho-Quinone Analogs through Inducing Apoptosis.

Twenty-seven L-shaped ortho-quinone analogs were designed and synthesized using a one pot double-radical synthetic strategy followed by removing methyl at C-3 of the furan ring and introducing a diverse side chain at C-2 of the furan ring. The synthetic derivatives were investigated for their cytotoxicity activities against human leukemia cells K562, prostate cancer cells PC3, and melanoma cells WM9. Compounds TB1, TB3, TB4, TB6, TC1, TC3, TC5, TC9, TC11, TC12, TC14, TC15, TC16, and TC17 exhibited a better broad-spectrum cytotoxicity on three cancer cells. TB7 and TC7 selectively displayed potent inhibitory activities on leukemia cells K562 and prostate cancer cells PC3, respectively. Further studies indicated that TB3, TC1, TC3, TC7, and TC17 could significantly induce the apoptosis of PC3 cells. TC1 and TC17 significantly induced apoptosis of K562 cells. TC1, TC11, and TC14 induced significant apoptosis of WM9 cells. The structure-activity relationships evaluation showed that removing methyl at C-3 of the furan ring and introducing diverse side chains at C-2 of the furan ring is an effective strategy for improving the anticancer activity of L-shaped ortho-quinone analogs.

A Novel Tanshinone Analog Exerts Anti-Cancer Effects in Prostate Cancer by Inducing Cell Apoptosis, Arresting Cell Cycle at G2 Phase and Blocking Metastatic Ability.

Prostate cancer (PCa), an epithelial malignant tumor, is the second common cause of cancer death among males in western countries. Thus, the development of new strategies is urgently needed. Tanshinones isolated from Salvia miltiorrhiza and its synthetic analogs show various biological activities including anticancer effects. Among them, the tanshinone analog 2-((Glycine methyl ester)methyl)-naphtho (TC7) is the most effective, with better selectivity and lower toxicity. Therefore, in this work, the effect of TC7 against PCa was investigated through assessing the molecular mechanisms regulating the growth, metastasis, and invasion of PCa cells. Human PCa cells, PC3 and LNCAP, were used to evaluate TC7 mechanisms of action in vitro, while male BALB/c nude mice were used for in vivo experiments by subjecting each mouse to a subcutaneous injection of PC3 cells into the right flank to evaluate TC7 effects on tumor volume. Our in vitro results showed that TC7 inhibited cell proliferation by arresting the cell cycle at G2/M through the regulation of cyclin b1, p53, GADD45A, PLK1, and CDC2/cyclin b1. In addition, TC7 induced cell apoptosis by regulating apoptosis-associated genes such as p53, ERK1, BAX, p38, BCL-2, caspase-8, cleaved-caspase-8, PARP1, and the phosphorylation level of ERK1 and p38. Furthermore, it decreased DNA synthesis and inhibited the migration and invasion ability by regulating VEGF-1 and MMP-9 protein expression. Our in vivo evidence supports the conclusion that TC7 could be considered as a potential promising chemotherapeutic candidate in the treatment of PCa.

Prediction of anastomotic leakage after anterior rectal resection.

OBJECTIVE: Anastomotic Leakage (AL) is one of the most common complications after resection of rectal cancer. Recognition of the incidence and risk factors related to AL is important. This study aimed develops a model that can predict anastomotic leakage after anterior rectal resection. METHODS: Data from 188 patients undergoing anterior resection of rectal cancer were collected for retrospective analysis. Patients were randomly divided in the development set and validation set at a 1:1 ratio. We first included age, sex, preoperative chemoradiotherapy, tumor size, degree of tumor differentiation, stage, TNM stage, lymph vascular invasion, distance, anastomotic method, diabetes, intraoperative time, intraoperative bleeding and smoking as candidates for variable selection with a LASSO method. A ROC curve was constructed with the validation set to assess the accuracy of the prediction model. RESULTS: AL occurred in 20 of 188 patients (10.6%). Preoperative chemoradiotherapy (p=0.04), medium degree of tumor differentiation (p=0.04), anastomotic method (p<0.01), intraoperative bleeding≥400ml (p<0.01), smoking (p<0.01), diabetes (p<0.01) were significantly related to AL. The area under the ROC curve of the prediction model is 0.952. CONCLUSIONS: This study developed a model that can predict anastomotic leakage after anterior rectal resection, which may aid the selection of preventive ileostomy and postoperative management.

A nanohybrid composed of MoS2 quantum dots and MnO2 nanosheets with dual-emission and peroxidase mimicking properties for use in ratiometric fluorometric detection and cellular imaging of glutathione.

A nanohybrid probe was fabricated from manganese dioxide nanosheets (MnO2 NSs), molybdenum disulfide quantum dots (MoS2 QDs) and o-phenylenediamine (OPD) for ratiometric detection of glutathione (GSH) in aqueous solutions and living cells. The MoS2 QDs act as the fluorescent "turn off-on" units. The MnO2 NSs have 3 functions, viz. (a) as fluorescence quencher, (b) as fluorescence initiator for oxidized OPD (ox OPD) and (c) as selective recognizer of GSH. The quenched blue fluorescence of the MoS2 QDs can be restored by introducing GSH that reduces the MnO2 NSs. However, the green fluorescence of ox OPD is decreased through the loss of peroxidase activity of MnO2 NSs in the presence of GSH. Therefore, the ratio of the fluorescence intensities at 560 and 400 nm (from ox OPD and MoS2 QDs, respectively) linearly decreases with increasing concentrations of GSH. Under the optimal conditions, the detection limit for GSH is as low as 90 nM. The method was successfully applied to the determination of GSH in human serum samples. This nanohybrid also is shown to be membrane-permeable and to have low cytotoxicity. This paved the way to intracellular sensing of GSH in living normal HFF and cancerous HeLa cells. Additionally, by combining with logic gate, this assay was successfully applied to visually discriminate changes in the intracellular GSH. The combination of ratiometric fluorometry and peroxidase mimicking can provide a wide range of application in bioanalysis and intracellular imaging. Graphical abstract Schematic representation of the ratiometric fluorometric detection and cellular imaging of glutathione using a nanohybrid composed of MoS2 quantum dots and MnO2 nanosheets with dual (blue and green emission and peroxidase mimicking properties.

Design and Synthesis of Flavonoidal Ethers and Their Anti-Cancer Activity In Vitro.

Flavonoids are well-characterized polyphenolic compounds with pharmacological and therapeutic activities. However, most flavonoids have not been developed into clinical drugs, due to poor bioavailability. Herein, we report a strategy to increase the drugability of flavonoids by constructing C(sp2)-O bonds and stereo- as well as regioselective alkenylation of hydroxyl groups of flavonoids with ethyl-2,3-butadienoate allenes. Twenty-three modified flavonoid derivatives were designed, synthesized, and evaluated for their anti-cancer activities. The results showed that compounds 4b, 4c, 4e, 5e, and 6b exhibited better in vitro inhibitory activity against several cancer cell lines than their precursors. Preliminary structure-activity relationship studies indicated that, in most of the cancer cell lines evaluated, the substitution on position 7 was essential for increasing cytotoxicity. The results of this study might facilitate the preparation or late-stage modification of complex flavonoids as anti-cancer drug candidates.

Phase-shifted pentafluorobutane nanoparticles for ultrasound imaging and ultrasound-mediated hypoxia modulation.

The integration of ultrasound (US) contrast enhancement with oxygen-loading nanoagents provide the synergistic strategy for simultaneously US imaging and hypoxic microenvironment modulation. Herein, we synthesize pentafluorobutane (PFB)-loading methoxy poly(ethylene glycol)-b-poly(l-lactide) (PLLA) nanoparticle as the novel US-contrast-enhanced agent and demonstrate that PFB@PLLA effectively loads oxygen. We characterize the nanosize, phase-transformation property and oxygen-loading amount of PFB@PLLA and investigate the effectiveness of these nanoagents in US-contrast-enhanced imaging. The PFB@PLLA displays a perfect temperature-responsive phase-transition property and its liquid-to-gas phase transition temperature is 45°C, which produces microbubbles in the targeted regions. Moreover, PFB@PLLA loads high amount of oxygen and US-triggering PFB@PLLA reoxygenation effectively inhibits the expression of hypoxia-related proteins (HIF-1α and CAIX), reduces lactate secretion and glycolysis, which modulates hypoxic microenvironment and inhibits cancer cell migration and invasion in vitro. This study demonstrates that the US contrast-enhanced activity of PFB@PLLAs and the promising utility of oxygen-loading nanoagents to improve hypoxic microenvironment.

Design, synthesis and bioactivity investigation of tetrandrine derivatives as potential anti-cancer agents.

Twenty-four 14-sulfonamide-tetrandrine derivatives as potential anti-cancer agents were synthesized. The synthetic derivatives were investigated for their cytotoxic activity against human cancer cell lines MDA-MB-231, PC3, WM9, HEL and K562. Initially, the IC50 values (50% inhibitory concentrations) of all of the compounds were determined. These derivatives exhibited potent, but distinct, inhibitory effects on the above-mentioned cell lines. Among them, compound 23, which was modified with a 2-naphthalenesulfonyl group at the 14-amino position, showed impressive inhibition of all five cancer cell lines, and especially of MDA-MB-231 cells with an IC50 value of 1.18 ± 0.14 µM. Further mechanism exploration showed that 23 induced potent apoptotic cell death on MDA-MB-231 cancer cells in a concentration-dependent manner. The results revealed that 23 might be a potential anti-cancer drug candidate.

MoS2 nanosheets with peroxidase mimicking activity as viable dual-mode optical probes for determination and imaging of intracellular hydrogen peroxide.

The authors describe a dual-mode (colorimetric-fluorometric) nanoprobe for H2O2 that was fabricated by covering molybdenum disulfide nanosheets (MoS2 NS) with ortho-phenylenediamine (OPD). The probe (OPD-MoS2 NS) was applied to the optical determination of H2O2, to the quantitation of cell numbers, and to the detection of intracellular concentrations of H2O2. Oxidation by H2O2 leads to a colored and fluorescent product (oxidized OPD) with absorption/excitation/fluorescence peaks at 450/450/557 nm. The nanoprobe can detect H2O2 in down to 500 nM concentrations, and HeLa cells at levels of 100 cells mL-1. The detection limit for intracellular H2O2 is in the 5.5 to 12.6 µM concentration range when the method is applied to cells at levels of 102-106 cells mL-1. Due to its good biocompatibility and easy cell uptake, the nanoprobe also permits sensitive fluorometric imaging of intracellular H2O2. It can also comparatively discriminate the change of intracellular oxidation state in living cancerous and normal cells. Graphical abstract Editor, we provided image with high resolution. Please find it in a folder name "MIAC-D-18-00081" in the FTP site. A dual-mode (colorimetric-fluorometric) detection nanoplatform based on OPD-modified MoS2 nanosheets is used to quantitatively detect H2O2, cell numbers and intracellular H2O2. The MoS2 nanoprobes also permit sensitive fluorescence imaging of intracellular H2O2, and can discriminate intracellular oxide states in living cancerous and normal cells.

Design and synthesis of novel C14-urea-tetrandrine derivatives with potent anti-cancer activity.

Tetrandrine is a dibenzyltetrahydroisoquinoline alkaloid, isolated from traditional Chinese medicinal plant Stephania tetrandra, with anti-tumor activity. Our previous study identified several derivatives of tetrandrine showing better activities than parental compound against human hepatocellular carcinoma cells. To increase diversity and cytotoxic activities of the original compound, a series of novel 14-urea-tetrandrine derivatives were synthesized through structural modification of tetrandrine. These derivaties demonstrated a moderate to strong anti-proliferative activities against human cell lines HEL and K562 (Leukemia), prostate (PC3), breast (MDA-MB-231) and melanoma (WM9). Compound 4g showed strongest cytotoxic effect against PC3 cells with IC50 value of 0.64 µM, which was 12-fold, 31-fold and 26-fold lower than the parental tetrandrine, 5-fluorouracil and cisplatin, respectively. Preliminary structure-activity relationship study indicated that urea subsititution was the key pharmacophore for the enhancement of their antitumor activities. Induction of apoprosis by 4g was associated with the activation of pro-apoptotic protein BAX and inhibition of antiapoptosis proteins survivin as well as Bcl-2. Moreover, activation of caspases led to increase cleavage of PARP, which further accelerates apoptotic cell death. These results reveal that the compound 4g may be used as a potential anticancer drug candidate.

Design, Synthesis and Anticancer Evaluation of Fangchinoline Derivatives.

Twenty fangchinoline derivatives were synthesized from the natural product fangchinoline, and their anticancer activities on human breast cancer MDA-MB-231 cell line, human prostate cancer PC3 cell line, human melanoma WM9 cell line and human leukaemia HEL and K562 cell lines were evaluated. The biological result showed that those derivatives exhibited potent activities on inhibiting cancer cell growth, and the structure-activity relationships were investigated. Among them, compound 4g, which was protected by benzoyl group in 7-phenolic position and nitrified in 14-position, showed impressive inhibition on all 5 cancer cell lines, especially WM9 cell line, with an IC50 value of 1.07 µM. Further mechanistic studies demonstrated that compound 4g may induce cancer cell death by apoptotic means. These research results suggested that compound 4g could be a lead for the further development toward an anticancer agent against human melanoma WM9 in the future.

EGFR-targeting PLGA-PEG nanoparticles as a curcumin delivery system for breast cancer therapy.

Poor bioavailability and non-specificity of chemotherapeutic agents are major challenges in breast cancer treatment. Antibodies and small molecules that block cell signaling pathways have shown promise in the clinic, but their application is also limited by the high costs and treatment dosages required. Novel therapies that aim to rapidly and specifically target malignant cells with long-lasting impact in the tumor microenvironment may ultimately improve clinical outcome in cancer patients. Here, we demonstrate that epidermal growth factor receptor (EGFR)-targeting GE11 peptides conjugated with PEGylated polylactic-co-glycolic acid (PLGA) nanoparticles can be used to effectively deliver an anti-cancer agent, curcumin, into EGFR-expressing MCF-7 cells in vitro and in vivo. Treatment of breast cancer cells and tumor-bearing mice with these curcumin-loaded nanoparticles gave rise to reduced phosphoinositide 3-kinase signaling, decreased cancer cell viability, attenuated drug clearance from the circulation, and suppressed tumor burden compared with free curcumin or non-EGFR targeting nanoparticles. The targeted nanoscale drug delivery system we describe here may provide a new strategy for the design of targeted cancer therapy vectors. Our study provides evidence that the efficacy of pharmacologic anti-cancer agents can be enhanced through their delivery in the form of modified nanoparticles that effectively target specific malignant cell types.

Ir-Catalyzed Asymmetric Total Synthesis of (-)-Communesin F.

The first catalytic asymmetric total synthesis of the heptacyclic alkaloid (-)-communesin F is described. A key step features an iridium-catalyzed asymmetric intermolecular cascade cyclization, constructing the lower N,N-aminal-containing CDEF tetracyclic core in one step. Another notable element is the closure of final ring system (A ring) via a facile reduction of a twisted amide and concomitant cyclization activated by mesylation of N,O-hemiaminal intermediate.

Iridium-Catalyzed Enantioselective Indole Cyclization: Application to the Total Synthesis and Absolute Stereochemical Assignment of (-)-Aspidophylline†A.

The first enantioselective total synthesis of (-)-aspidophylline A, including assignment of its absolute configuration has been accomplished. A key element of the synthesis is a highly enantioselective indole allylic alkylation/iminium cyclization cascade which was developed by employing a combination of Lewis acid activation and an iridium/ligand catalyst. This strategy relies on the direct use of 2,3-disubstituted indoles with secondary allylic alcohols appended at C2 and heteronucleophiles appended at C3, indoles which are easily prepared from simple starting materials under C-H activation conditions.