Two New Isospirostanol-Type Saponins from the Bulbs of Lilium Brownii and Their Anti-Hepatocarcinogenic Activity.

Bulbs of Lilium brownii, commonly known as "Bai-he" in China, serve both edible and medicinal purposes in clinical practice. In this study, two new isospirostanol-type saponins were isolated from L. brownii, and their structures were identified by spectroscopic method, and absolute configurations were elucidated by comprehensive analysis of spectral data obtained from combined acid hydrolysis. Two compounds were finally identified as 3-O-[α-L-rhamnopyranosyl-(1→2)-ß-D-glucopyranoside]-(22R,25R)-5α-spirosolane-3ß-ol (1) and 3-O-{α-L-rhamnopyranosyl-(1→2)-[ß-D-glucopyranosyl-(1→4)]-ß-D-glucopyranoside}-(22R,25R)-5α-spirosolane-3ß-ol (2), respectively. Further, we found that compound 2 significantly suppressed the proliferation of SMMC-7721 and HepG2 cells with IC50 values of 26.3±1.08 µM and 30.9±1.59 µM, whereas compound 1 didn't inhibit both of the two hepatocellular carcinoma. Subsequently, compound 2 effectively decreased the levels of interleukin-1ß and tumor necrosis factor-α and the expression of Bcl-2, and increased the expression of Bax and Caspase-3 proteins. Which indicated that the anti-hepatocellular carcinoma effect of compound 2 involves reducing the level of inflammation and inducing apoptosis.

Anticancer activity of oleanolic acid and its derivatives modified at A-ring and C-28 position.

Oleanolic acid (OA) is a five-ring triterpenoid compound, which is widely present in plants. Due to a wide range of pharmacological activities, oleanolic acid has attracted more and more attention. However, oleanolic acid is insoluble in water and has low bioavailability, which limits its clinical application. In this review, we focus on summarizing the anti-cancer activity and mechanism of the A ring or C-28 carboxyl modified derivatives of OA since 2015, to determine the strength of its anti-cancer effectiveness and evaluate whether it could be used as a clinical anti-cancer drug.

Partially fluorinated nanoemulsions for 19F MRI-fluorescence dual imaging cell tracking.

Fluorine-19 magnetic resonance imaging (19F MRI) has been a technology of choice for in vivo cell tracking, in which perfluorocarbons (PFCs) nanoemulsions are the most used 19F MRI agents. However, the peculiar physicochemical properties of PFCs may lead to poor cell uptake and misleading cell tracking results. Herein, we employed partially fluorinated aromatic agents to formulate paramagnetic nanoemulsions as novel 19F MRI-fluorescence (FL) dual imaging agents for cell tracking. With the intramolecular π-π interaction, low density and fluorine content, the partially fluorinated agents enable considerable solubilities of functional agents and short relaxation times, which facilitates convenient preparation of stable, biocompatible, and multifunctional nanoemulsions with high 19F MRI sensitivity. Replacing PFCs in 19F MRI nanoemulsions with readily available partially fluorinated aromatic agents may address many issues associated with PFCs and provide a novel strategy for high-performance 19F MRI agents of broad biomedical applications.

Synthesis of trifluoromethylated aza-BODIPYs as fluorescence-19F MRI dual imaging and photodynamic agents.

Dual-imaging agents with highly sensitive fluorescence (FL) imaging and highly selective fluorine-19 magnetic resonance imaging (19F MRI) are valuable for biomedical research. At the same time, photosensitizers with a high reactive oxygen species (ROS) generating capability are crucial for photodynamic therapy (PDT) of cancer. Herein, a series of tetra-trifluoromethylated aza-boron dipyrromethenes (aza-BODIPYs) were conveniently synthesized from readily available building blocks and their physicochemical properties, including ultraviolet-visible (UV-Vis) absorption, FL emission, photothermal efficacy, ROS generating efficacy, and 19F MRI sensitivity, were systematically investigated. An aza-BODIPY with 12 symmetrical fluorines was identified as a potent FL-19F MRI dual-imaging traceable photodynamic agent. It was found that the selective introduction of trifluoromethyl (CF3) groups into aza-BODIPYs may considerably improve their UV absorption, FL emission, photothermal efficacy, and ROS generating properties, which lays the foundation for the rational design of trifluoromethylated aza-BODIPYs in biomedical applications.

Hydrofluorocarbon nanoparticles for 19F MRI-fluorescence dual imaging and chemo-photodynamic therapy.

The synergistic chemotherapy and photodynamic therapy (PDT) may significantly improve the cancer therapeutic efficacy, in which fluorinated nanoemulsions are highly advantageous for their ability to deliver oxygen to hypoxic tumors and provide fluorine-19 magnetic resonance imaging (19F MRI). The low solubility of chemotherapy drugs and photosensitizers in current perfluorocarbon (PFC)-based 19F MRI agents usually leads to complicated formulations or chemical modifications and low nanoemulsion stability and performance. Herein, we employ readily available partially fluorinated ethyl 2-(3,5-bis(trifluoromethyl)phenyl)acetate as the 19F MRI agent and the solvent to dissolve the cancer stem cell inhibitor salinomycin and the photosensitizer ICG for the convenient preparation of 19F MRI-fluorescence dual imaging and synergistic chemotherapy, photothermal and photodynamic therapy nanoemulsions. The chemotherapy drug salinomycin has a high solubility in the partially fluorinated reagent, facilitating its high loading and efficient delivery. Paramagnetic iron(III) (Fe3+) is incorporated into the nanoemulsion through the dissolved chelator to significantly improve the 19F MRI sensitivity. Furthermore, the dissolved fluorinated 2-pyridone enables the efficient capture and sustained release of singlet oxygen in the dark for high PDT efficacy. The multifunctional nanoemulsions show sensitive 19F MRI and fluorescence dual imaging capability and high synergistic chemotherapy, photothermal and photodynamic therapy efficacy in cancer cells, which may be valuable oxygen delivery, sustained ROS generating and release, dual imaging and multimodal therapy agents for hypoxic tumors. This study provided a convenient co-solubilization strategy for the rapid construction of multifunctional theranostics for hypoxic tumors.

Perfluoro-tert-butanol: a cornerstone for high performance fluorine-19 magnetic resonance imaging.

As a versatile quantification and tracking technology, 19F magnetic resonance imaging (19F MRI) provides quantitative "hot-spot" images without ionizing radiation, tissue depth limit, and background interference. However, the lack of suitable imaging agents severely hampers its clinical application. First, because the 19F signals are solely originated from imaging agents, the relatively low sensitivity of MRI technology requires high local 19F concentrations to generate images, which are often beyond the reach of many 19F MRI agents. Second, the peculiar physicochemical properties of many fluorinated compounds usually lead to low 19F signal intensity, tedious formulation, severe organ retention, etc. Therefore, the development of 19F MRI agents with high sensitivity and with suitable physicochemical and biological properties is of great importance. To this end, perfluoro-tert-butanol (PFTB), containing nine equivalent 19F and a modifiable hydroxyl group, has outperformed most perfluorocarbons as a valuable building block for high performance 19F MRI agents. Herein, we summarize the development and application of PFTB-based 19F MRI agents and analyze the strategies to improve their sensitivity and physicochemical and biological properties. In the context of PFC-based 19F MRI agents, we also discuss the challenges and prospects of PFTB-based 19F MRI agents.

Quantitatively Fine-Tuning the Physicochemical and Biological Properties of Peptidic Polymers through Monodisperse PEGylation.

In biomedicine, PEGylation is one of the most successful strategies to modify the physicochemical and biological properties of peptides, proteins, and other biomacromolecules. Because of the polydisperse nature of regular PEGs and limited PEGylation strategies, it is challenging to quantitatively fine-tune and accurately predict the properties of biomacromolecules after PEGylation. However, such fine-tuning and prediction may be crucial for their biomedical applications. Herein, some monodisperse PEGylation strategies, including backbone PEGylation, side-chain PEGylation, and highly branched PEGylation, have been developed. In a comparative fashion, the impact of PEGylation strategies and monodisperse PEG sizes on the physicochemical and biological properties, including lipophilicity, thermosensitivity, biocompatibility, plasma stability, and drug delivery capability, of peptidic polymers has been quantitatively studied. It was found that the physicochemical and biological properties of PEGylated peptidic polymers can be quantitatively fine-tuned and accurately predicted through these monodisperse PEGylation strategies. After the comparative study, a side-chain monodisperse PEGylated peptidic polymer was chosen as fluorine-19 magnetic resonance and fluorescence dual-imaging traceable drug delivery vehicle. Our study may not only promote the transformation of PEGylation from an empirical technology to a quantitative science but also shed light on the rational design of PEGylated biomaterials and pharmaceutics.

[Effects of global change on soil fauna diversity: A review].

Terrestrial ecosystem consists of aboveground and belowground components, whose interaction affects the ecosystem processes and functions. Soil fauna plays an important role in biogeochemical cycles. With the recognizing of the significance of soil fauna in ecosystem processes, increasing evidences demonstrated that global change has profound effects on soil faunima diversity. The alternation of land use type, the increasing temperature, and the changes in precipitation pattern can directly affect soil fauna diversity, while the increase of atmospheric CO2 concentration and nitrogen deposition can indirectly affect the soil fauna diversity by altering plant community composition, diversity, and nutrient contents. The interactions of different environmental factors can co-affect the soil fauna diversity. To understand the effects of different driving factors on soil fauna diversity under the background of climate change would facilitate us better predicting how the soil fauna diversity and related ecological processes changed in the future.

Specificity responses of grasshoppers in temperate grasslands to diel asymmetric warming.

BACKGROUND: Global warming is characterized by not only an increase in the daily mean temperature, but also a diel asymmetric pattern. However, most of the current studies on climate change have only concerned with the mean values of the warming trend. Although many studies have been conducted concerning the responses of insects to climate change, studies that address the issue of diel asymmetric warming under field conditions are not found in the literature. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a field climate manipulative experiment and investigated developmental and demographic responses to diel asymmetric warming in three grasshopper species (an early-season species Dasyhippus barbipes, a mid-season species Oedaleus asiaticus, and a late-season species Chorthippus fallax). It was found that warming generally advanced the development of eggs and nymphs, but had no apparent impacts on the hatching rate of eggs, the emergence rate of nymphs and the survival and fecundity of adults in all the three species. Nighttime warming was more effective in advancing egg development than the daytime warming. The emergence time of adults was differentially advanced by warming in the three species; it was advanced by 5.64 days in C. fallax, 3.55 days in O. asiaticus, and 1.96 days in D. barbipes. This phenological advancement was associated with increases in the effective GDDs accumulation. CONCLUSIONS/SIGNIFICANCE: Results in this study indicate that the responses of the three grasshopper species to warming are influenced by several factors, including species traits, developmental stage, and the thermal sensitivity of the species. Moreover, species with diapausing eggs are less responsive to changes in temperature regimes, suggesting that development of diapausing eggs is a protective mechanism in early-season grasshopper for avoiding the risk of pre-winter hatching. Our results highlight the need to consider the complex relationships between climate change and specificity responses of invertebrates.

Prevalence of metabolic syndrome in bipolar patients initiating acute-phase treatment: a 6-month follow up.

AIMS: To evaluate the prevalence of metabolic syndrome (MetS) and its correlates in patients with bipolar disorder (BD) during acute-phase treatment in southern China. METHODS: This study included 148 BD patients presenting with acute mood symptoms and 65 healthy controls at entry. Sociodemographic characteristics were noted for all participants. For patients, lifestyle information (alcohol, smoking, and exercise habits) and clinical characteristics were also collected. Patients were followed up for 6 months after the commencement of pharmacological treatment. Using the Chinese Medical Association Diabetes Branch criteria, MetS prevalence rates were calculated at entry and recalculated for patients at months 1, 3, and 6. RESULTS: At baseline, MetS was presented in 11.5% of the patients; overweight, 34.5%; low high-density lipoprotein cholesterol, 15.5%; hypertriglyceridemia, 29.1%; hypertension, 14.9%; and hyperglycemia, 5.4%. Compared with controls, the patients had a significantly higher prevalence of MetS and all its components except for hyperglycemia (P < 0.05). In the regression analysis, history of hypertension, presence of diabetes, and alcohol drinking were associated with MetS. During the follow-up period, rates of MetS and overweight increased gradually and stably, hypertriglyceridemia and low high-density lipoprotein cholesterol increased significantly in the first month and then remained stable, and hypertension and hyperglycemia remained stable all the time. CONCLUSIONS: These data show that MetS is highly prevalent in Chinese BD patients. Weight gain and dyslipidemia result from a short period of treatment. Early interventions for weight gain and dyslipidemia are warranted.