Young Sca-1+ bone marrow stem cell-derived exosomes preserve visual function via the miR-150-5p/MEKK3/JNK/c-Jun pathway to reduce M1 microglial polarization.

BACKGROUND: Polarization of microglia, the resident retinal immune cells, plays important roles in mediating both injury and repair responses post-retinal ischemia-reperfusion (I/R) injury, which is one of the main pathological mechanisms behind ganglion cell apoptosis. Aging could perturb microglial balances, resulting in lowered post-I/R retinal repair. Young bone marrow (BM) stem cell antigen 1-positive (Sca-1+) cells have been demonstrated to have higher reparative capabilities post-I/R retinal injury when transplanted into old mice, where they were able to home and differentiate into retinal microglia. METHODS: Exosomes were enriched from young Sca-1+ or Sca-1- cells, and injected into the vitreous humor of old mice post-retinal I/R. Bioinformatics analyses, including miRNA sequencing, was used to analyze exosome contents, which was confirmed by RT-qPCR. Western blot was then performed to examine expression levels of inflammatory factors and underlying signaling pathway proteins, while immunofluorescence staining was used to examine the extent of pro-inflammatory M1 microglial polarization. Fluoro-Gold labelling was then utilized to identify viable ganglion cells, while H&E staining was used to examine retinal morphology post-I/R and exosome treatment. RESULTS: Sca-1+ exosome-injected mice yielded better visual functional preservation and lowered inflammatory factors, compared to Sca-1-, at days 1, 3, and 7 days post-I/R. miRNA sequencing found that Sca-1+ exosomes had higher miR-150-5p levels, compared to Sca-1- exosomes, which was confirmed by RT-qPCR. Mechanistic analysis found that miR-150-5p from Sca-1+ exosomes repressed the mitogen-activated protein kinase kinase kinase 3 (MEKK3)/JNK/c-Jun axis, leading to IL-6 and TNF-α downregulation, and subsequently reduced microglial polarization, all of which contributes to reduced ganglion cell apoptosis and preservation of proper retinal morphology. CONCLUSION: This study elucidates a potential new therapeutic approach for neuroprotection against I/R injury, via delivering miR-150-5p-enriched Sca-1+ exosomes, which targets the miR-150-5p/MEKK3/JNK/c-Jun axis, thereby serving as a cell-free remedy for treating retinal I/R injury and preserving visual functioning.

Designing an alkali-metal-like superatom Ca3B for ambient nitrogen reduction to ammonia.

Converting earth-abundant nitrogen (N2) gas into ammonia (NH3) under mild conditions is one of the most important issues and a long-standing challenge in chemistry. Herein, a new superatom Ca3B was theoretically designed and characterized to reveal its catalytic performance in converting N2 into NH3 by means of density functional theory (DFT) computations. The alkali-metal-like identity of this cluster is verified by its lower vertical ionization energy (VIE, 4.29 eV) than that of potassium (4.34 eV), while its high stability was guaranteed by the large HOMO-LUMO gap and binding energy per atom (Eb). More importantly, this well-designed superatom possesses unique geometric and electronic features, which can fully activate N2via a "double-electron transfer" mechanism, and then convert the activated N2 into NH3 through a distal reaction pathway with a small energy barrier of 0.71 eV. It is optimistically hoped that this work could intrigue more endeavors to design specific superatoms as excellent catalysts for the chemical adsorption and reduction of N2 to NH3.

Biomimetic amphiphilic FAAP NPs nanoparticles: Synthesis, characterization and antivirus activity.

Antiviral agents based on natural products have attracted substantial attention in clinical applications for their distinct biological activities,molecular structuralmultiformities, and low biotoxicities. Ferulic acid (FA) with apigenin propaneto form an esterified FA derivative (FAAP).Herein, we designed a CsPbBr3-modified chitosan oligosaccharide, a biomimetic nanoplatform that could load with FAAP. After self-assembly by combining FAAP with CsPbBr3-modified chitosan oligosaccharide (FAAP NPs), the resulting nanoparticles (FAAP NPs) showed high antioxidant and anti-inflammatory activities for enhancing the inhibition of porcineparvovirus.FAAP NPs exhibited no signs of acute toxicity in vitro or in vivo. DPPH and ABST are widely used for quantitative determination of antioxidant capacity. FAAP NPs exhibited excellent DPPH and ABTS radical scavenging abilities. In addition, we found that FAAP NPs inhibited PPV infection-induced PK-15 cell apoptosis, which was associated with regulating antioxidant and anti-inflammatory signaling pathways. Importantly, we showed that FAAP NPs blocked PPV infection-induced mitochondrial apoptosis in PK-15 cells via a p53/BH3 domain molecular-dependent mechanism.

DFT study on the adsorption of 5-fluorouracil on B40, B39M, and M@B40 (M = Mg, Al, Si, Mn, Cu, Zn).

Based on density functional theory, the adsorption behavior of 5-fluorouracil (5-Fu) on B40 and its derivatives has been explored. It was observed that 5-Fu prefers to combine with the corner boron atom of the B40 cage via one of its oxygen atoms, forming a strong polar covalent B-O bond. The adsorption energy of 5-Fu on B40 was calculated to be -11.15 kcal mol-1, and thus, it can be duly released from B40 by protonation in the slightly acidic environment of tumor tissue, which makes for reducing the toxic and side effects of this drug. Additionally, the substituent and embedding effect of Mg, Al, Si, Mn, Cu, and Zn atoms on the drug delivery performance of B40 have been also considered. We hope this work could offer some implications for the potential application of boron-based nanomaterials, such as B40 in drug delivery.

On the Role of Alkali-Metal-Like Superatom Al12 P in Reduction and Conversion of Carbon Dioxide.

Developing efficient catalysts for the conversion of CO2 into fuels and value-added chemicals is of great significance to relieve the growing energy crisis and global warming. With the assistance of DFT calculations, it was found that, different from Al12 X (X=Be, Al, and C), the alkali-metal-like superatom Al12 P prefers to combine with CO2 via a bidentate double oxygen coordination, yielding a stable Al12 P(η2 -O2 C) complex containing an activated radical anion of CO2 (i.e., CO2 .- ). Thereby, this compound could not only participate in the subsequent cycloaddition reaction with propylene oxide but also initiate the radical reaction with hydrogen gas to form high-value chemicals, revealing that Al12 P can play an important role in catalyzing these conversion reactions. Considering that Al12 P has been produced in laboratory and is capable of absorbing visible light to drive the activation and transformation of CO2 , it is anticipated that this work could guide the discovery of additional superatom catalysts for CO2 transformation and open up a new research field of superatom catalysis.

Coinage metalides: a new class of excess electron compounds with high stability and large nonlinear optical responses.

The possibility of using coinage metal atoms as excess electron acceptors is examined for the first time by designing a new class of M+-1-M'- (M = Li, Na, and K; M' = Cu, Ag, and Au) compounds termed "coinage metalides" on the basis of an intriguing Janus-type all-cis1,2,3,4,5,6-hexafluorocyclohexane (1) molecule. Under the large facial polarization of 1, the outermost ns1 electrons of alkali metal atoms can be transferred to coinage metal atoms, forming diffuse excess electrons around them. Consequently, the resulting M+-1-Cu- and M+-1-Ag- compounds exhibit significantly large nonlinear optical (NLO) responses. In particular, these novel M+-1-M'- compounds exhibit much higher stability (larger VIEs and Ec values) than that of the corresponding M+·1·M'- (M, M' = Li, Na, and K) alkalides. We hope this work could open up new possibilities for NLO material design by using coinage metal atoms as excess electron acceptors and, on the other hand, attract more experimental interest and efforts to synthesize such stable compounds in the laboratory.

Hyperbranched rolling circle amplification (HRCA)-based fluorescence biosensor for ultrasensitive and specific detection of single-nucleotide polymorphism genotyping associated with the therapy of chronic hepatitis B virus infection.

Detection of specific genes related to drug action can provide scientific guidance for personalized medicine. Taking the detection of a single-nucleotide polymorphism (SNP) genotyping related to the chronic hepatitis B virus (HBV) therapy as an example, a novel biosensor with high sensitivity and selectivity was developed based on the hyperbranched rolling circle amplification (HRCA) in this work. The single-base mutant DNA (mutDNA) sequence can perfectly hybridize with the specially designed discrimination padlock probe and initiate the HRCA reaction. Subsequently, a great abundant of double-strand DNA sequences were released and a strong fluorescence signal can be detected after adding SYBR Green I. In particular, the enhanced fluorescence intensity exhibits a linear relationship with the logarithm of mutDNA concentration ranging from 0.1 nM to 40 nM with a low detection limit of 0.05 nM. However, when there was even a single base mismatch in the target DNA, the HRCA was suppressed and fluorescence response process could not occur, resulting in a high selectivity of this biosensor. Moreover, this detection strategy also performs well in human serums, demonstrating its potential application in detecting SNPs in real biological samples.

Can Coinage Metal Atoms Be Capable of Serving as an Excess Electron Source of Alkalides with Considerable Nonlinear Optical Responses?

Alkalides, as a representative kind of excess electron compounds, have been demonstrated to be potential nonlinear optical (NLO) materials with large static first hyperpolarizabilities (ß0). The possibility of utilizing coinage metal atoms as a novel excess electron source to design a series of alkalides, i.e., (M@36adz)M' (M = Cu, Ag, and Au; M' = Li, Na, and K), was examined by density functional theory calculations. The alkalide characteristics of these compounds are guaranteed by their HOMOs and VIE values as well as NBO analysis. In particular, all proposed alkalides exhibit considerable first hyperpolarizabilities (ß0) up to 61 590 au, indicating that they can be considered as novel NLO molecules of high performance. Moreover, a larger cage-complexant has been considered, and the resulting (Ag+@TriPip222)K- alkalide possesses a remarkably large ß0 value of 180 068 au. We hope that this work will provide a new recipe for designing excess electron compounds and, on the other hand, attract more research interest and efforts in exploring new, unconventional alkalides.

On the feasibility of designing hyperalkali cations using superalkali clusters as ligands.

The possibility of using superalkali clusters instead of alkali atoms as ligands to design a class of cationic compounds, referred to as hyperalkali cations, has been examined by using gradient-corrected density functional theory. By taking typical superalkalis (FLi2, OLi3, and NLi4) as examples, a series of hyperalkali cations ML2+ [M = (super)halogen; L = superalkali] have been constructed and investigated. Calculational results show that all the superalkali moieties preserve their geometric and electronic integrity in these proposed cations. The stability of these studied cations is guaranteed by the strong ionic bonds between superalkali ligand and (super)halogen core, as well as their large highest occupied molecular orbital-lowest unoccupied molecular orbital gaps and positive dissociation energies. In particular, all these proposed cations possess lower vertical electron affinities (2.36-3.56 eV) than those of their corresponding cationic superalkali ligands, verifying their hyperalkali nature. We, therefore, hope that this study will provide an approach to obtain new species with excellent reducing capability by utilizing various superalkalis as building blocks.

Theoretical Study of the Substituent Effects on the Nonlinear Optical Properties of a Room-Temperature-Stable Organic Electride.

Excess-electron compounds can be considered as novel candidates for nonlinear optical (NLO) materials because of their large static first hyperpolarizabilities (ß0 ). A room-temperature-stable, excess-electron compound, that is, the organic electride Na@(TriPip222), was successfully synthesized by the Dye group (J. Am. Chem. Soc. 2005, 127, 12416). In this work, the ß0 of this electride was first evaluated to be 1.13×106  au, which revealed its potential as a high-performance NLO material. In particular, the substituent effects of different substituents on the structure, electride character, and NLO response of this electride were systemically studied for the first time by density functional theory calculations. The results revealed that the ß0 of Na@(TriPip222) could be further increased to 8.30×106  au by introducing a fluoro substituent, whereas its NLO response completely disappeared if one nitryl group was introduced because the nitro-group substitution deprived the material of its electride identity. Moreover, herein the dependence of the NLO properties on the number of substituents and their relative positions was also detected in multifluoro-substituted Na@(TriPip222) compounds.

ClpP-deletion impairs the virulence of Legionella pneumophila and the optimal translocation of effector proteins.

BACKGROUND: The opportunistic bacterial pathogen Legionella pneumophila uses substrate effectors of Dot/Icm type IVB secretion system (T4BSS) to accomplish survival and replication in amoebae cells and mammalian alveolar macrophages. During the conversion between its highly resistant, infectious dormant form and vigorously growing, uninfectious replicative form, L. pneumophila utilizes a complicated regulatory network in which proteolysis may play a significant role. As a highly conserved core protease, ClpP is involved in various cellular processes as well as virulence in bacteria, and has been proved to be required for the expression of transmission traits and cell division of L. pneumophila. RESULTS: The clpP-deficient L. pneumophila strain failed to replicate and was digested in the first 3 h post-infection in mammalian cells J774A.1. Further investigation demonstrates that the clpP deficient mutant strain was unable to escape the endosome-lysosomal pathway in host cells. We also found that the clpP deficient mutant strain still expresses T4BSS components, induces contact-dependent cytotoxicity and translocate effector proteins RalF and LegK2, indicating that its T4BSS was overall functional. Interestingly, we further found that the translocation of several effector proteins is significantly reduced without ClpP. CONCLUSIONS: The data indicate that ClpP plays an important role in regulating the virulence and effector translocation of Legionella pneumophila.

Stability and Nonlinear Optical Response of Alkalides that Contain a Completely Encapsulated Superalkali Cluster.

Guided by density functional theory (DFT) computations, a new series of superalkali-based alkalides, namely FLi2 (+) (aza222)K(-) , OLi3 (+) (aza222)K(-) , NLi4 (+) (aza222)K(-) , and Li3 (+) (aza222)K(-) were designed with various superalkali clusters embedded into an aza222 cage-complexant. These species possess diverse isomeric structures in which the encapsulated superalkalis preserve their identities and behave as alkali metal atoms. The results show that these novel alkalides possess larger complexation energies and enhanced hyperpolarizabilities (ß0 ) compared with alkali-metal-based and previous superalkali-based clusters. Especially, a prominent structural dependence of ß0 is observed for these studied compounds. Hence, the geometric factors that affect the nonlinear optical (NLO) response of such alkalides is elucidated in detail in this work. This study not only provides novel candidates for alkalides, it also offers an effective way to enhance the NLO response and stability of alkalides.

A theoretical study on superalkali-doped nanocages: unique inorganic electrides with high stability, deep-ultraviolet transparency, and a considerable nonlinear optical response.

By doping an Al12N12 nanocage with superalkali Li3O, a series of Li3O@Al12N12 compounds were theoretically designed and investigated for the first time. Computational results reveal that these species contain diffuse excess electrons, and thus can be regarded as inorganic electrides of a new type. As expected, these proposed electrides possess considerable first hyperpolarizabilities (ß0) up to 1.86 × 10(7) au. In particular, the lowest-energy Li3O@Al12N12 exhibits high stability and excellent deep-ultraviolet transparency. Moreover, the effects of superalkali and nanocage subunits on the NLO responses of M3O@Al12N12 (M = Li, Na, K) and Li3O@X12Y12 (X = B, Al; Y = N, P) are systemically investigated. Results show that the respective substitution of Na3O and B12P12 for Li3O and Al12N12 can bring a larger ß0 for such electrides. This study may be significant in terms of providing an effective strategy to design thermally stable inorganic electrides as potential high-performance NLO molecules.

Can Fluorinated Molecular Cages Be Utilized as Building Blocks of Hyperhalogens?

Based on the density functional theory for exchange-correlation potential, fluorocarbon molecular cages are investigated as building blocks of hyperhalogens. By utilizing C8 F7 as a ligand, a series of hyperhalogen anions, that is, M(C8 F7 )2 (-) (M=Li, Na, and K) and M(C8 F7 )3 (-) (M=Be, Mg, and Ca), are modeled. Calculations show that all the C8 F7 moieties preserve their geometric and electronic integrity in these anions. These anionic molecules possess larger vertical electron detachment energies (5.11-6.45 eV) than that of C8 F7 (-) , verifying their hyperhalogen nature. Moreover, it is also revealed that using larger fluorinated cage C10 F9 as ligands can bring about hyperhalogen anions with larger vertical electron detachment energies. The stability of these studied anions is determined by their large HOMO-LUMO gaps and positive dissociation energies of predetermined possible fragmentation pathways. It is hoped this study will provide an approach for the construction of new types of hyperhalogens and stimulate more research in superatom chemistry.

Theoretical characterization of a series of N5-based aromatic hyperhalogen anions.

Hyperhalogens are a class of highly electronegative molecules whose electron affinities even exceed those of their superhalogen ligands. Such species can serve as new oxidizing agents, biocatalysts, and building blocks of unusual salts, and hence are important to the chemical industry. Utilizing stable N5(-) as the ligand, a series of aromatic hyperhalogen anions, namely mononuclear M(N5)(k+1)(-) (M = Li, Be, B) and dinuclear M2(N5)(2k+1)(-) (M = Li, Be), have been reported here for the first time. Calculation results based on the density functional theory revealed that all the N5(-) subunits preserve their structural and electronic integrity as well as aromatic characteristics in these anions. Especially, these anionic molecules exhibit larger vertical electron detachment energies (6.76-7.86 eV) than that of the superhalogen ligand N5(-), confirming their hyperhalogen nature. The stability of these studied anions is guaranteed by their large HOMO-LUMO gaps, and positive dissociation energies of predetermined fragmentation pathways. We hope this work will not only provide evidence of a new type of hyperhalogen molecule but also stimulate more research interest and efforts in the amazing superatom realm.

Efficient post-disaster patient transportation and transfer: experiences and lessons learned in emergency medical rescue in Aceh after the 2004 Asian tsunami.

This descriptive study aimed to present experiences and lessons learned in emergency medical rescue after the 2004 Asian tsunami in terms of transportation and transfer of patients and coordination of medical rescue forces. After the tsunami, numerous rescue institutions and international organizations rushed to Aceh province to aid in the rescue work. To coordinate various aspects of medical rescue efforts, an airport-based joint patient transfer center was developed. Within the framework of the joint transport center, rescue teams, militaries, and international institutions worked together to jointly triage, rapidly treat, and transfer patients. As members of the Chinese International Search and Rescue team, we were involved in the rescue efforts in the joint patient transfer center, and treated and transferred a total of 217 injured patients, the majority of whom were triaged as level II, followed by level III, and level I. The top three diseases were trauma/wound infection, respiratory system disease, and digestive system disease. The airport-based joint patient transfer center provided an efficient mechanism for successfully coordinating various aspects of the medical rescue efforts to transfer patients. Large-scale air transport, available health resources, and effective triage criteria also played an essential role in patient transportation and transfer.

[Detection of plasticizers in edible essence by near-infrared spectrometry].

Based on the initial near-infrared spectrum of edible essence samples and its mixture with DEHP and DINP, we chose the wavelength ranges of 8,800 - 8,540 and 7,500 - 5,085 cm-1 to use the principal component analysis (PCA) method to distinguish these three types of samples. The correct rate of the identification is proved to be 100%. Meanwhile, we measured the content of DEHP and DINP (with the concentration ranging between 0 and 100 mg.kg-1) in the edible essence and established the quantitative analysis model by using partial least squares (PLS). It was found that the relative errors of the prediction results of DEHP and DINP are -1.23% - 3% and -1% - 3.6%, respectively, and the relative root-mean-square errors of prediction (RRMSEP) of them are 1.39 and 0.98, respectively. This study provides a simple, rapid and accurate method to detect the additive dosage of plasticizing agents in edible essence in the food industry.

Simultaneous determination of 143Nd/144Nd and 147Sm/144Nd ratios and Sm-Nd contents from the same filament loaded with purified Sm-Nd aliquot from geological samples by isotope dilution thermal ionization mass spectrometry.

Isotope dilution thermal ionization mass spectrometry (ID-TIMS) is the standard technique used to achieve precise (143)Nd/(144)Nd and (147)Sm/(144)Nd isotope ratios and accurate elemental concentrations of Sm-Nd. However, in previous studies, purified Sm and Nd fractions must be individually loaded onto different filaments for their accurate determination using TIMS because of severe isobaric interferences. Thus, the classical ID-TIMS technique is time consuming and laborious. In this study, a new method is proposed, which is able to acquire both ratios of (143)Nd/(144)Nd and (147)Sm/(144)Nd and concentrations of Sm-Nd simultaneously on the same filament arrangement. The measurement time and filament consumption are reduced by 50% with the current method, and therefore, the operation cost of TIMS is significantly reduced. A mixed (152)Sm-(148)Nd spike was employed to achieve accurate results after spike subtraction and isobaric interference corrections. Results obtained from a series of standard rock samples are in good agreement with recommended values, within ±0.003% for the (143)Nd/(144)Nd ratio and ±1% for the (147)Sm/(144)Nd ratio.

Rapid and precise determination of Sr and Nd isotopic ratios in geological samples from the same filament loading by thermal ionization mass spectrometry employing a single-step separation scheme.

Thermal ionization mass spectrometry (TIMS) offers the excellent precision and accuracy of the Sr and Nd isotopic ratio analysis for geological samples, but this method is labour intensive, expensive and time-consuming. In this study, a new analytical protocol by TIMS is presented that aims at improving analytical efficiency and cutting down experimental cost. Using the single-step cation exchange resin technique, mixed Sr and rare earth elements (REEs) fractions were separated from matrix and evaporated to dryness. Afterwards, mixed Sr+REEs fractions were dissolved and loaded onto the same Re filament using 1 µL of 2 M HCl. Then, Sr and Nd were sequentially measured without venting using TIMS. In contrast to conventional TIMS methods, the merits of this analytical protocol are its cost- and time-saving adaptations. The applicability of our method is evaluated by replicated measurements of (87)Sr/(86)Sr and (143)Nd/(144)Nd for nine international silicate rock reference materials, spanning a wide range of bulk compositions. The typical internal precision in this study is ca. 0.001% (RSE) for (87)Sr/(86)Sr and (143)Nd/(144)Nd; the analytical results obtained for these standard rocks show a good agreement with reported values, indicating the effectiveness of the proposed method.