A rhodamine-based fluorescent probe used to determine nitroxyl (HNO) in lysosomes.

The reactive nitrogen species (RNS) in lysosomes play a major role during the regulation of lysosomal microenvironment. Nitroxyl (HNO) belongs to active nitrogen species (RNS) and is becoming a potential diagnostic and therapeutic biomarker. However, the complex synthesis routes of HNO in biosystem always hinder the exact determination of HNO in living cells. Here, a rhodamine-based fluorescent probe used to determine nitroxyl (HNO) in lysosomes was constructed and synthesized. 2-(Diphenylphosphino)benzoate was utilized as the sensing unit for HNO and morpholine was chose as the targeting group for lysosome. Before the addition of HNO, the probe displayed a spirolactone structure and almost no fluorescence was found. After the addition of HNO, the probe existed as a conjugated xanthene form and an intense green fluorescence was observed. The fluorescent probe possessed fast response (3 min) and high selectivity for HNO. Furthermore, fluorescence intensity of the probe linearly related with the HNO concentration in the range of 6.0 × 10-8 to 6.0 × 10-5 mol L-1. The detection limit was found to be 1.87 × 10-8 mol L-1 for HNO. Moreover, the probe could selectively targeted lysosome with excellent biocompatibility and had been effectually utilized to recognize exogenous HNO in A549 cells.

[Bacterial Community Structure of Typical Lake Sediments in Yinchuan City and Its Response to Heavy Metals].

Lake wetlands are extremely important and special ecosystems, which are important for regional water resource storage, environmental protection, and biodiversity maintenance. Sediment bacteria are an important component of lake ecosystems and are a major driver of biogeochemical cycling in lakes. In order to investigate the community structure of bacteria in typical lake sediments in Yinchuan City and their influencing factors, three typical lakes in Yinchuan City (Yuehai Lake, Mingcui Lake, and Xiniu Lake) were selected for the study and surface sediments were collected in January, April, July, and October 2021. The composition of the sediment bacterial community was examined using 16S rDNA high-throughput sequencing technology, and the response relationships between them and heavy metals were explored. The results showed that the ecological hazard coefficient for heavy metals in the sediments of three typical lakes in Yinchuan City was far less than 40, and the ecological hazard index was far less than 150, all of which indicated a minor ecological hazard. There were no significant differences in bacterial community diversity among the three lakes, but there were significant variations in diversity among the lakes in different seasons and significant differences in community composition. The dominant phyla (top three in terms of relative abundance) in Yuehai Lake, Mingcui Lake, and Xiniu Lake were Proteobacteria, Bacteroidetes, and Chloroflexi. The dominant lower orders were Gammaproteobacteria, Alphaproteobacteria, and Deltaproteobacteria. The main divergent species that occurred at the phylum level in typical lakes in Yinchuan were Proteobacteria, Bacteroidetes, Euryarchaeota, Firmicutes, Actinobacteria, and Acidobacteria. The sediment bacterial community structure of Yuehai Lake was significantly correlated with Cu, Fe, Mn, Zn, As, and Pb; the sediment bacterial community structure of Lake Mingcui was significantly correlated with Fe, Pb, and Cr; and the sediment bacterial community structure of Xiniu Lake was not significantly correlated with heavy metals. The types and contents of sediment heavy metals had a significant effect on the bacterial community structure of sediments in Yinchuan Yuehai Lake and Mingcui Lake and were important environmental factors that caused changes in the bacterial community structure of lake sediments.

Anti-Cancer Potential of Phytochemicals: The Regulation of the Epithelial-Mesenchymal Transition.

A biological process called epithelial-mesenchymal transition (EMT) allows epithelial cells to change into mesenchymal cells and acquire some cancer stem cell properties. EMT contributes significantly to the metastasis, invasion, and development of treatment resistance in cancer cells. Current research has demonstrated that phytochemicals are emerging as a potential source of safe and efficient anti-cancer medications. Phytochemicals could disrupt signaling pathways related to malignant cell metastasis and drug resistance by suppressing or reversing the EMT process. In this review, we briefly describe the pathophysiological properties and the molecular mechanisms of EMT in the progression of cancers, then summarize phytochemicals with diverse structures that could block the EMT process in different types of cancer. Hopefully, these will provide some guidance for future research on phytochemicals targeting EMT.

An ICT-FRET-based ratiometric fluorescent probe for hydrogen polysulfide based on a coumarin-naphthalimide derivative.

Hydrogen polysulfide (H2Sn, n > 1), as one of the important members of reactive sulfur species (RSS), plays a vital part in the processes of both their physiology and pathology. In this work, a ratiometric fluorescent probe for H2Sn had been designed and prepared based on the combination mechanism of intramolecular charge transfer (ICT) and fluorescence resonance energy transfer (FRET). The probe chose a coumarin derivative as the energy donor, a naphthalimide derivative as the energy acceptor and 2-fluoro-5-nitrobenzoate as the H2Sn recognition group. When H2Sn was not present in the system, the ICT process of the naphthalimide acceptor was inhibited and the FRET process from the coumarin donor to the naphthalimide acceptor was turned off. When H2Sn was added, both ICT and FRET occurred due to the nucleophilic substitution-cyclization reactions between the probe and hydrogen polysulfide. In addition, the ratio value of the emission intensities at 550 nm and 473 nm (I550 nm/I473 nm) of this probe had a good linear relationship with H2Sn concentration in the range of 6.0 × 10-7-5.0 × 10-5 mol·L-1, and a detection limit of 1.8 × 10-7 mol·L-1 was obtained. The developed probe had high selectivity and sensitivity, as well as good biocompatibility. Additionally, the probe had been used to successfully image both indigenous and exogenous hydrogen polysulfide in A549 cells using confocal microscope.

A naphthalimide-based and Golgi-targetable fluorescence probe for quantifying hypochlorous acid.

The Golgi apparatus (GA) is a vital organelle in biological systems and excess reactive oxygen species (ROS) is produced during stress in the Golgi apparatus. Hypochlorous acid (HOCl) is a significant reactive oxygen species and has strong oxidative and antibacterial activity, but excessive secretion of hypochlorous acid can affect Golgi structure or function abnormally, it will lead to a series of diseases including Alzheimer's disease, neurodegenerative diseases, autoimmune diseases, and Parkinson's disease. In present work, a novel fluorescent probe for Golgi localization utilizing naphthalimide derivatives was constructed to detect hypochlorous acid. The fluorescent probe used a derivatived 1,8-naphthalimide as the emitting fluorescence group, phenylsulfonamide as the localization group and dimethylthiocarbamate as the sensing unit. When HOCl was absent, the intramolecular charge transfer (ICT) process of the developed probe was hindered and the probe exhibited a weak fluorescence. When HOCl was present, the ICT process occurred and the probe showed strong green fluorescence. When the HOCl concentration was altered from 5.0 × 10-7 to 1.0 × 10-5 mol·L-1, the fluorescence intensity of the probe well linearly correlated with the HOCl concentration. The detection limit of 5.7 × 10-8 mol·L-1 was obtained for HOCl. The HOCl fluorescent probe possessed a rapid reaction time, a high selectivity and a broad working pH scope. In addition, the probe possessed good biocompatibility and had been magnificently employed to image Golgi HOCl in Hela cells. These characteristics of the probe demonstrated its ability to be used for sensing endogenous and exogenous hypochlorous acids within the Golgi apparatus of living cells.

Rhodamine-Based Fluorescent Probe for Highly Selective Determination of Hg2.

The determination of mercuric ions (Hg2+) in environmental and biological samples has attracted the attention of researchers lately. In the present work, a novel turn-on Hg2+ fluorescent probe utilizing a rhodamine derivative had been constructed and prepared. The probe could highly sensitively and selectively sense Hg2+. In the presence of excessive Hg2+, the probe displayed about 52-fold fluorescence enhancement in 50% H2O/CH3CH2OH (pH, 7.24). In the meantime, the colorless solution of the probe turned pink upon adding Hg2+. Upon adding mercuric ions, the probe interacted with Hg2+ and formed a 1:1 coordination complex, which had been the basis for recognizing Hg2+. The probe displayed reversible dual colorimetric and fluorescence sensing of Hg2+ because rhodamine's spirolactam ring opened upon adding Hg2+. The analytical performances of the probe for sensing Hg2+ were also studied. When the Hg2+ concentration was altered in the range of 8.0 × 10-8 to 1.0 × 10-5 mol L-1, the fluorescence intensity showed an excellent linear correlation with Hg2+ concentration. A detection limit of 3.0 × 10-8 mol L-1 had been achieved. Moreover, Hg2+ in the water environment and A549 cells could be successfully sensed by the proposed probe.

Inhibition of BAG3 enhances the anticancer effect of shikonin in hepatocellular carcinoma.

Human hepatocellular carcinoma (HCC) is the most frequent cancer worldwide with a poor prognosis. Tumor-specific pyruvate kinase M2 (PKM2) is essential for cancer metabolism and tumorigenesis. Shikonin, a specific inhibitor of PKM2, but not PKM1, exhibits significant anticancer effect in HCC, and was deemed as a promising drug for cancer therapy. However, shikonin-mediated bypass signaling in HCC remained unclear. Here, we performed forward/reverse stable isotope labeling with amino acids in cell culture (SILAC)-based proteomics to identify the early molecular events controlled by shikonin. We demonstrated for the first time that shikonin could induce the nuclear translocation of PKM2 for recruiting Nrf2, and transcriptionally activated Nrf2 downstream target gene BAG3, therefore increasing protective effect to sustain cell survival. Knockdown of BAG3 by si-RNA significantly potentiated the anticancer effect of shikonin. These findings provided the first evidence of a new noncanonical function of inhibited PKM2 could act as a transcriptional coactivator of Nrf2 in cancer survival, highlight that shikonin in combined with BAG3 inhibitor could be a promising therapeutic strategy for HCC therapy.

Paclitaxel-loaded magnetic nanocrystals for tumor neovascular-targeted theranostics: an amplifying synergistic therapy combining magnetic hyperthermia with chemotherapy.

A combination of chemotherapy and targeted magnetic hyperthermia (TMH) via a designed magnetic nanocrystal (MNC) drug delivery system was considered as an effective tumor synergistic therapy strategy. In this paper, we successfully synthesized tumor neovascular-targeted Mn-Zn ferrite MNCs, which encapsulated paclitaxel (PTX) in a biocompatible PEG-phospholipid (DSPE-PEG2000) layer and surface, simultaneously coupled with a tripeptide of arginine-glycine-aspartic acid (RGD). The high-performance RGD-modified MNC loaded with PTX (MNCs-PTX@RGD) embodied excellent magnetic properties, including high-contrast magnetic resonance imaging (MRI) and remarkable magnetically induced heat generation ability. We established the mouse model bearing subcutaneous 4T1 breast tumor, and demonstrated that MNCs-PTX@RGD could be effectively located in the tumor neovascular epithelial cells under the guidance of in vivo MRI. Notably, MNCs-PTX@RGD could easily penetrate into the tumor tissue from the tumor-fenestrated vascular networks for capturing a sufficient temperature (around 43 °C) exposed to an alternative current magnetic field (ACMF, 2.58 kA m-1, 390 kHz), leading to an effective TMH effect. Subsequently, the TMH-mediated temperature elevation accelerated the PTX release from the inner lipid layer, promoting the synergetic thermo-chemotherapy in vivo. The amplifying synergistic treatment strategy obviously improved the anti-tumor efficacy of MNCs-PTX@RGD, and simultaneously increased the survival time of the mice to more than 46 days, which provided a broad development prospect in clinical applications.

Intercalation Pseudocapacitance Boosting Ultrafast Sodium Storage in Prussian Blue Analogs.

Great expectation is placed on sodium-ion batteries with high rate capability to satisfy multiple requirements in large-scale energy storage systems. However, the large ionic radius and high mass of Na+ hamper its kinetics in the case of diffusion-controlled mechanisms in conventional electrodes. In this study, a unique intercalation pseudocapacitance has been demonstrated in low-vacancy copper hexacyanoferrate, achieving outstanding rate capability. The minimization of the [Fe(CN)6 ] vacancy enables unhindered diffusion pathways for Na+ and little structural change during the Fe2+ /Fe3+ redox reaction, eliminating solid-state diffusion limits. Moreover, the Cu+ /Cu2+ couple is unexpectedly activated, realizing a record capacity for copper hexacyanoferrate. A capacity of 86 mAh g-1 is obtained at 1 C, of which 50 % is maintained under 100 C and 70 % is achieved at 0 °C. Such intercalation pseudocapacitance might shed light on exploiting high-rate electrodes among Prussian blue analogs for advanced sodium-ion batteries.

Wet Chemical Synthesis of Non-solvated Rod-Like α'-AlH3 as a Hydrogen Storage Material.

Aluminum hydride (AlH3) is a promising candidate for hydrogen storage due to its high hydrogen density of 10 wt%. Several polymorphs of AlH3 (e.g., α, ß, and γ) have been successfully synthesized by wet chemical reaction of LiAlH4 and AlCl3 in ether solution followed by desolvation. However, the synthesis process of α'-AlH3 from wet chemicals still remains unclear. In the present work, α'-AlH3 was synthesized first by the formation of the etherate AlH3 through a reaction of LiAlH4 and AlCl3 in ether solution. Then, the etherate AlH3 was heated at 60°C under an ether gas atmosphere and in the presence of excess LiAlH4 to remove the ether ligand. Finally, α'-AlH3 was obtained by ether washing to remove the excess LiAlH4. It is suggested that the desolvation of the etherate AlH3 under an ether gas atmosphere is essential for the formation of α'-AlH3 from the etherate AlH3. The as-synthesized α'-AlH3 takes the form of rod-like particles and can release 7.7 wt% hydrogen in the temperature range 120-200°C.

Purification and Characterization of JZTx-14, a Potent Antagonist of Mammalian and Prokaryotic Voltage-Gated Sodium Channels.

Exploring the interaction of ligands with voltage-gated sodium channels (NaVs) has advanced our understanding of their pharmacology. Herein, we report the purification and characterization of a novel non-selective mammalian and bacterial NaVs toxin, JZTx-14, from the venom of the spider Chilobrachys jingzhao. This toxin potently inhibited the peak currents of mammalian NaV1.2⁻1.8 channels and the bacterial NaChBac channel with low IC50 values (<1 µM), and it mainly inhibited the fast inactivation of the NaV1.9 channel. Analysis of NaV1.5/NaV1.9 chimeric channel showed that the NaV1.5 domain II S3⁻4 loop is involved in toxin association. Kinetics data obtained from studying toxin⁻NaV1.2 channel interaction showed that JZTx-14 was a gating modifier that possibly trapped the channel in resting state; however, it differed from site 4 toxin HNTx-III by irreversibly blocking NaV currents and showing state-independent binding with the channel. JZTx-14 might stably bind to a conserved toxin pocket deep within the NaV1.2⁻1.8 domain II voltage sensor regardless of channel conformation change, and its effect on NaVs requires the toxin to trap the S3⁻4 loop in its resting state. For the NaChBac channel, JZTx-14 positively shifted its conductance-voltage (G⁻V) and steady-state inactivation relationships. An alanine scan analysis of the NaChBac S3⁻4 loop revealed that the 108th phenylalanine (F108) was the key residue determining the JZTx-14⁻NaChBac interaction. In summary, this study provided JZTx-14 with potent but promiscuous inhibitory activity on both the ancestor bacterial NaVs and the highly evolved descendant mammalian NaVs, and it is a useful probe to understand the pharmacology of NaVs.

Understanding Moisture and Carbon Dioxide Involved Interfacial Reactions on Electrochemical Performance of Lithium-Air Batteries Catalyzed by Gold/Manganese-Dioxide.

Lithium-air (Li-air) battery works essentially based on the interfacial reaction of 2Li + O2 ↔ Li2O2 on the catalyst/oxygen-gas/electrolyte triphase interface. Operation of Li-air batteries in ambient air still remains a great challenge despite the recent development, because some side reactions related to moisture (H2O) and carbon dioxide (CO2) will occur on the interface with the formation of some inert byproducts on the surface of the catalyst. In this work, we investigated the effect of H2O and CO2 on the electrochemical performance of Li-air batteries to evaluate the practical operation of the batteries in ambient air. The use of a highly efficient gold/δ-manganese-dioxide (Au/δ-MnO2) catalyst helps to understand the intrinsic mechanism of the effect. We found that H2O has a more detrimental influence than CO2 on the battery performance when operated in ambient air. The battery operated in simulated dry air can sustain a stable cycling up to 200 cycles at 400 mA g(-1) with a relatively low polarization, which is comparable with that operated in pure O2. This work provides a possible method to operate Li-air batteries in ambient air by using optimized catalytic electrodes with a protective layer, for example a hydrophobic membrane.

Au-nanocrystals-decorated δ-MnO2 as an efficient catalytic cathode for high-performance Li-O2 batteries.

A Li-O2 battery works based on the reversible formation and decomposition of Li2O2, which is insulating and highly reactive. Designing a catalytic cathode capable of controlling Li2O2 growth recently became a challenge to overcome this barrier. In this work, we present a new design of catalytic cathode by growing porous Au/δ-MnO2 electrocatalyst directly on a conductive substrate. We found that Au/δ-MnO2 can catalyze the directed growth of Li2O2 into a thin/small form, only inside porous δ-MnO2, and along the surface of δ-MnO2 sheets. We proposed the catalytic mechanism of Au/δ-MnO2, where Au plays a critical role in catalyzing the nucleation, crystallization and conformal growth of Li2O2 on δ-MnO2 sheets. Li-O2 batteries with an Au/δ-MnO2 catalytic cathode showed excellent electrochemical performance due to this favorable Li2O2 growth habit. The battery yielded a high capacity of 10,600 mA h g(-1) with a low polarization of 0.91 V at 100 mA g(-1). Superior cycling stability could be achieved in both capacity-limited (500 mA h g(-1), 165 times at 400 mA g(-1)) and unlimited (ca. 3000 mA h g(-1), 50 cycles at 800 mA g(-1)) modes.

Assessing phenological change and climatic control of alpine grasslands in the Tibetan Plateau with MODIS time series.

The Tibetan Plateau, a unique cold and dry region recognized as the Earth's third pole, is primarily composed of alpine grasslands (>60 %). While a warming climate in the plateau is being recorded, phenology of alpine grasslands and its climatic dependencies are less investigated. This study tests the feasibility of the frequently observed Moderate Resolution Imaging Spectroradiometer (MODIS) time series (500 m, 8 days) in examining alpine phenology in the plateau. A set of phenological metrics are extracted from the MODIS Normalized Difference Vegetation Index (NDVI) series in each year, 2000-2010. A nonparametric Mann-Kendall trend analysis is performed to find the trends of these phenological metrics, which are then linked to monthly climatic records in the growing season. Opposite trends of phenological change are observed between the east and west of the plateau, with delayed start of season, peak date, and end of season in the west and advanced phenophases in the east. The correlation analysis indicates that precipitation, with a decreasing trend in the west and increasing trend in the east, may serve as the primary driver of the onset and peak dates of greenness. Temperature increases all over the plateau. While the delay of the end of season in the west could be related to higher late-season temperature, its advance in the east needs further investigation in this unique cold region. This study demonstrates that frequent satellite observations are able to extract phenological features of alpine grasslands and to provide spatiotemporally detailed base information for long-term monitoring on the plateau under rapid climate change.

Preferential c-axis orientation of ultrathin SnS2 nanoplates on graphene as high-performance anode for Li-ion batteries.

A SnS2/graphene (SnS2/G) hybrid was synthesized by a facile one-step solvothermal route using graphite oxide, sodium sulfide, and SnCl4·5H2O as the starting materials. The formation of SnS2 and the reduction of graphite oxide occur simultaneously. Ultrathin SnS2 nanoplates with a lateral size of 5-10 nm are anchored on graphene nanosheets with a preferential (001) orientation, forming a unique plate-on-sheet structure. The electrochemical tests showed that the nanohybrid exhibits a remarkably enhanced cycling stability and rate capability compared with bare SnS2. The excellent electrochemical properties of SnS2/G could be ascribed to the in situ introduced graphene matrix which offers two-dimensional conductive networks, disperses and immobilizes SnS2 nanoplates, buffers the volume changes during cycling, and directs the growth of SnS2 nanoplates with a favorable orientation.