Prognostic significance of serum globulin in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: We investigated the association between serum globulin levels upon hospital admission and in-hospital short-term outcomes in acute ischemic stroke (AIS) patients. METHODS: A total of 3,127 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included in the present study. We divided patients into 4 groups according to their level of admission serum globulin: Q1 (<23.5 g/L), Q2 (23.5-26.4 g/L), Q3 (26.4-29.9 g/L), and Q4 (≥29.9 g/L). Logistic regression models were used to estimate the effect of serum globulin on the short-term outcomes, including all cause in-hospital mortality, poor outcome upon discharge (modified Rankin Scale score ≥3) and in-hospital pneumonia in AIS patients. RESULTS: The median National Institutes of Health Stroke Scale (NIHSS) score was 4.0 (IQR, 2.0-7.0). The risk of in-hospital mortality was significantly higher in patients with highest serum globulin level (Q4) compared to those with lowest (Q1) (adjusted odds ratio [OR] 2.30; 95% confidence interval [CI], 1.12-4.70; P-trend =0.026). The highest serum globulin level (Q4) was associated with a 1.32-fold and 1.62-fold increase in the risk of poor outcome upon discharge (adjusted OR 1.32; 95% CI, 1.00-1.75; P-trend = 0.070) and in-hospital pneumonia (adjusted OR 1.62; 95% CI, 1.18-2.23; P-trend = 0.001) in comparison to Q1 after adjustment for potential covariates. CONCLUSIONS: A high level of serum globulin upon hospital admission was independently associated with all cause in-hospital mortality, poor outcome upon discharge and in-hospital pneumonia in relative mild AIS patients.

Atomically precise gold nanocrystal molecules with surface plasmon resonance.

Since Faraday's pioneering work on gold colloids, tremendous scientific research on plasmonic gold nanoparticles has been carried out, but no atomically precise Au nanocrystals have been achieved. This work reports the first example of gold nanocrystal molecules. Mass spectrometry analysis has determined its formula to be Au(333)(SR)(79) (R = CH(2)CH(2)Ph). This magic sized nanocrystal molecule exhibits fcc-crystallinity and surface plasmon resonance at approximately 520 nm, hence, a metallic nanomolecule. Simulations have revealed that atomic shell closing largely contributes to the particular robustness of Au(333)(SR)(79), albeit the number of free electrons (i.e., 333 - 79 = 254) is also consistent with electron shell closing based on calculations using a confined free electron model. Guided by the atomic shell closing growth mode, we have also found the next larger size of extraordinarily stability to be Au(~530)(SR)(~100) after a size-focusing selection--which selects the robust size available in the starting polydisperse nanoparticles. This work clearly demonstrates that atomically precise nanocrystal molecules are achievable and that the factor of atomic shell closing contributes to their extraordinary stability compared to other sizes. Overall, this work opens up new opportunities for investigating many fundamental issues of nanocrystals, such as the formation of metallic state, and will have potential impact on condensed matter physics, nanochemistry, and catalysis as well.

Chiral 38-gold-atom nanoclusters: synthesis and chiroptical properties.

Enantioselective synthesis of chiral Au38 nanoclusters is achieved with chiral 2-phenylpropane-1-thiol (abbreviated as R/S-PET, organic soluble), captopril and glutathione (water soluble) as the respective ligand. The circular dichroism (CD) spectra of Au38 (R-PET)24 and Au38 (S-PET)24 show multiple bands which are precisely mirror-imaged, while their normal optical absorption spectra are identical with each other and also superimposable with that of the racemic Au38 (SCH2 CH2 Ph)24 nanoclusters. The observed CD signals are not from the chiral ligands themselves (which only give rise to CD signals in the UV (<250 nm), rather than in the visible wavelength region). Chiral Au38 nanoclusters with different types of ligands are further compared. Although the Au38 core is intrinsically chiral, different chiral ligands are found to largely influence the chiroptical response of the overall nanocluster. Thus, the chiral response of ligand-protected nanoclusters has both contributions from the metal core and the ligand shell around it. These optically active nanoclusters hold promise in future applications such as chiral sensing and catalysis.

Multifaceted role of SARS-CoV-2 structural proteins in lung injury.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third human coronavirus to cause acute respiratory distress syndrome (ARDS) and contains four structural proteins: spike, envelope, membrane, and nucleocapsid. An increasing number of studies have demonstrated that all four structural proteins of SARS-CoV-2 are capable of causing lung injury, even without the presence of intact virus. Therefore, the topic of SARS-CoV-2 structural protein-evoked lung injury warrants more attention. In the current article, we first synopsize the structural features of SARS-CoV-2 structural proteins. Second, we discuss the mechanisms for structural protein-induced inflammatory responses in vitro. Finally, we list the findings that indicate structural proteins themselves are toxic and sufficient to induce lung injury in vivo. Recognizing mechanisms of lung injury triggered by SARS-CoV-2 structural proteins may facilitate the development of targeted modalities in treating COVID-19.

Quantum sized gold nanoclusters with atomic precision.

Gold nanoparticles typically have a metallic core, and the electronic conduction band consists of quasicontinuous energy levels (i.e. spacing δ ≪ k(B)T, where k(B)T is the thermal energy at temperature T (typically room temperature) and k(B) is the Boltzmann constant). Electrons in the conduction band roam throughout the metal core, and light can collectively excite these electrons to give rise to plasmonic responses. This plasmon resonance accounts for the beautiful ruby-red color of colloidal gold first observed by Faraday back in 1857. On the other hand, when gold nanoparticles become extremely small (<2 nm in diameter), significant quantization occurs to the conduction band. These quantum-sized nanoparticles constitute a new class of nanomaterial and have received much attention in recent years. To differentiate quantum-sized nanoparticles from conventional plasmonic gold nanoparticles, researchers often refer to the ultrasmall nanoparticles as nanoclusters. In this Account, we chose several typical sizes of gold nanoclusters, including Au(25)(SR)(18), Au(38)(SR)(24), Au(102)(SR)(44), and Au(144)(SR)(60), to illustrate the novel properties of metal nanoclusters imparted by quantum size effects. In the nanocluster size regime, many of the physical and chemical properties of gold nanoparticles are fundamentally altered. Gold nanoclusters have discrete electronic energy levels as opposed to the continuous band in plasmonic nanoparticles. Quantum-sized nanoparticles also show multiple optical absorption peaks in the optical spectrum versus a single surface plasmon resonance (SPR) peak at 520 nm for spherical gold nanocrystals. Although larger nanocrystals show an fcc structure, nanoclusters often have non-fcc atomic packing structures. Nanoclusters also have unique fluorescent, chiral, and magnetic properties. Due to the strong quantum confinement effect, adding or removing one gold atom significantly changes the structure and the electronic and optical properties of the nanocluster. Therefore, precise atomic control of nanoclusters is critically important: the nanometer precision typical of conventional nanoparticles is not sufficient. Atomically precise nanoclusters are represented by molecular formulas (e.g. Au(n)(SR)(m) for thiolate-protected ones, where n and m denote the respective number of gold atoms and ligands). Recently, major advances in the synthesis and structural characterization of molecular purity gold nanoclusters have made in-depth investigations of the size evolution of metal nanoclusters possible. Metal nanoclusters lie in the intermediate regime between localized atomic states and delocalized band structure in terms of electronic properties. We anticipate that future research on quantum-sized nanoclusters will stimulate broad scientific and technological interests in this special type of metal nanomaterial.

Atomic-level alloying and de-alloying in doped gold nanoparticles.

Atomically precise alloying and de-alloying processes for the formation of Ag-Au and Cu-Au nanoparticles of 25-metal-atom composition (referred to as Ag(x)Au(25-x)(SR)18 and Cu(x)Au(25-x)(SR)18 , in which R = CH2CH2Ph) are reported. The identities of the particles were determined by matrix-assisted laser desorption ionization mass spectroscopy (MALDI-MS). Their structures were probed by fragmentation analysis in MALDI-MS and comparison with the icosahedral structure of the homogold Au25(SR)18 nanoparticles (an icosahedral Au13 core protected by a shell of Au12(SR)18). The Cu and Ag atoms were found to preferentially occupy the 13-atom icosahedral sites, instead of the exterior shell. The number of Ag atoms in Ag(x)Au(25-x)(SR)18 (x = 0-8) was dependent on the molar ratio of Ag(I)/Au(III) precursors in the synthesis, whereas the number of Cu atoms in Cu(x)Au(25-x)(SR)18 (x = 0-4) was independent of the molar ratio of Cu(II)/Au(III) precursors applied. Interestingly, the Cu(x)Au(25-x)(SR)18 nanoparticles show a spontaneous de-alloying process over time, and the initially formed Cu(x)Au(25-x)(SR)18 nanoparticles were converted to pure Au25(SR)18. This de-alloying process was not observed in the case of alloyed Ag(x)Au(25-x)(SR)18 nanoparticles. This contrast can be attributed to the stability difference between Cu(x)Au(25-x)(SR)18 and Ag(x)Au(25-x)(SR)18 nanoparticles. These alloyed nanoparticles are promising candidates for applications such as catalysis.

Evolution of nonlinear optical properties: from gold atomic clusters to plasmonic nanocrystals.

Atomic clusters of metals are an emerging class of extremely interesting materials occupying the intermediate size regime between atoms and nanoparticles. Here we report the nonlinear optical (NLO) characteristics of ultrasmall, atomically precise clusters of gold, which are smaller than the critical size for electronic energy quantization (∼2 nm). Our studies reveal remarkable features of the distinct evolution of the optical nonlinearity as the clusters progress in size from the nonplasmonic regime to the plasmonic regime. We ascertain that the smallest atomic clusters do not show saturable absorption at the surface plasmon wavelength of larger gold nanocrystals (>2 nm). Consequently, the third-order optical nonlinearity in these ultrasmall gold clusters exhibits a significantly lower threshold for optical power limiting. This limiting efficiency, which is superior to that of plasmonic nanocrystals, is highly beneficial for optical limiting applications.

Experimental and computational investigation of Au25 clusters and CO2: a unique interaction and enhanced electrocatalytic activity.

Atomically precise, inherently charged Au(25) clusters are an exciting prospect for promoting catalytically challenging reactions, and we have studied the interaction between CO(2) and Au(25). Experimental results indicate a reversible Au(25)-CO(2) interaction that produced spectroscopic and electrochemical changes similar to those seen with cluster oxidation. Density functional theory (DFT) modeling indicates these changes stem from a CO(2)-induced redistribution of charge within the cluster. Identification of this spontaneous coupling led to the application of Au(25) as a catalyst for the electrochemical reduction of CO(2) in aqueous media. Au(25) promoted the CO(2) → CO reaction within 90 mV of the formal potential (thermodynamic limit), representing an approximate 200-300 mV improvement over larger Au nanoparticles and bulk Au. Peak CO(2) conversion occurred at -1 V (vs RHE) with approximately 100% efficiency and a rate 7-700 times higher than that for larger Au catalysts and 10-100 times higher than those for current state-of-the-art processes.

Monoplatinum doping of gold nanoclusters and catalytic application.

We report single-atom doping of gold nanoclusters (NCs), and its drastic effects on the optical, electronic, and catalytic properties, using the 25-atom system as a model. In our synthetic approach, a mixture of Pt(1)Au(24)(SC(2)H(4)Ph)(18) and Au(25)(SC(2)H(4)Ph)(18) was produced via a size-focusing process, and then Pt(1)Au(24)(SC(2)H(4)Ph)(18) NCs were obtained by selective decomposition of Au(25)(SC(2)H(4)Ph)(18) in the mixture with concentrated H(2)O(2) followed by purification via size-exclusion chromatography. Experimental and theoretical analyses confirmed that Pt(1)Au(24)(SC(2)H(4)Ph)(18) possesses a Pt-centered icosahedral core capped by six Au(2)(SC(2)H(4)Ph)(3) staples. The Pt(1)Au(24)(SC(2)H(4)Ph)(18) cluster exhibits greatly enhanced stability and catalytic activity relative to Au(25)(SC(2)H(4)Ph)(18) but a smaller energy gap (E(g) ≈ 0.8 eV vs 1.3 eV for the homogold cluster).

Well-defined nanoclusters as fluorescent nanosensors: a case study on Au(25) (SG)(18).

The fluorescence of nanoparticles has attracted much attention in recent research, but in many cases the underlying mechanisms are difficult to evaluate due to the polydispersity of nanoparticles and their unknown structures, in particular the surface structures. Recent breakthroughs in the syntheses and structure determinations of well-defined gold nanoclusters provide opportunities to conduct in-depth investigations. Devising well-defined nanocluster sensors based on fluorescence change is of particular interest not only for scientific studies but also for practical applications. Herein, the potential of the glutathionate (SG)-capped Au(25) nanocluster as a silver ion sensor is evaluated. The Ag(+) detection limit of approximately 200 nM, based on the fluorescence enhancement and good linear fluorescence response in the silver ion concentration range from 20 nM to 11 µM, in combination with the good selectivity among 20 types of metal cations, makes Au(25) (SG)(18) a good candidate for fluorescent sensors for silver ions. Further experiments reveal three important factors responsible for the unique fluorescence enhancement caused by silver ions: 1) the oxidation state change of Au(25) (SG)(18) ; 2) the interaction of neutral silver species (Ag(0) , reduced by Au(25) (SG)(18) (-) ) with Au(25) (SG)(18) ; and 3) the interaction of Ag(+) with Au(25) (SG)(18.) Experiments demonstrate the very different chemistry of hydrophobic Au(25) (SC(2) H(4) Ph)(18) and hydrophilic Au(25) (SG)(18) in the reaction with silver ions. This work indicates another potential application of gold nanoclusters, offers new strategies for nanocluster-based chemical sensing, and reveals a new way to influence nanocluster chemistry for potential applications.

Chiral Au25 nanospheres and nanorods: synthesis and insight into the origin of chirality.

Chirality in nanoparticles is an intriguing phenomenon. Herein, we have devised a well-defined gold nanoparticle system for investigating the origin of chirality in nanoparticles. We have designed chiral thiols (R- and S-isomers) and synthesized chiral gold nanoparticles composed of 25 gold atoms and 18 ligands, referred to as Au(25)(pet)(18), where pet represents chirally modified phenylethylthiolate -SCH(2)CH(CH(3))Ph at the 2-position. These optically active nanoparticles are close analogues of the optically nonactive phenylethylthioalte-capped Au(25)(pet)(18) nanoparticles, and the latter's crystal structure is known. On the basis of the atomic and electronic structures of these well-defined Au(25) nanoparticles, we have explicitly revealed that the ligands and surface gold atoms of Au(25)(pet)(18) play a critical role in effecting the circular dichroism responses from the nanoparticles. Similar effects are also observed in chiral Au(25) rods. The mixing of electronic states of ligands with those of surface gold atoms constitutes the fundamental origin of chirality in such nanoparticles.

Total structure and electronic properties of the gold nanocrystal Au36(SR)24.

A golden opportunity: the total structure of a Au(36)(SR)(24) nanocluster reveals an unexpected face-centered-cubic tetrahedral Au(28) kernel (magenta). The protecting layer exhibits an intriguing combination of binding modes, consisting of four regular arch-like staples and the unprecedented appearance of twelve bridging thiolates (yellow). This unique protecting network and superatom electronic shell structure confer extreme stability and robustness.

Quantum-sized gold nanoclusters: bridging the gap between organometallics and nanocrystals.

This Concept article provides an elementary discussion of a special class of large-sized gold compounds, so-called Au nanoclusters, which lies in between traditional organogold compounds (e.g., few-atom complexes, <1 nm) and face-centered cubic (fcc) crystalline Au nanoparticles (typically >2 nm). The discussion is focused on the relationship between them, including the evolution from the Au⋅⋅⋅Au aurophilic interaction in Au(I) complexes to the direct Au-Au bond in clusters, and the structural transformation from the fcc structure in nanocrystals to non-fcc structures in nanoclusters. Thiolate-protected Au(n)(SR)(m) nanoclusters are used as a paradigm system. Research on such nanoclusters has achieved considerable advances in recent years and is expected to flourish in the near future, which will bring about exciting progress in both fundamental scientific research and technological applications of nanoclusters of gold and other metals.

Crystal structures of Au2 complex and Au25 nanocluster and mechanistic insight into the conversion of polydisperse nanoparticles into monodisperse Au25 nanoclusters.

We previously reported a size-focusing conversion of polydisperse gold nanoparticles capped by phosphine into monodisperse [Au(25)(PPh(3))(10)(SC(2)H(4)Ph)(5)Cl(2)](2+) nanoclusters in the presence of phenylethylthiol. Herein, we have determined the crystal structure of [Au(25)(PPh(3))(10)(SC(2)H(4)Ph)(5)Cl(2)](2+) nanoclusters and also identified an important side-product-a Au(I) complex formed in the size focusing process. The [Au(25)(PPh(3))(10)(SC(2)H(4)Ph)(5)Cl(2)](2+) cluster features a vertex-sharing bi-icosahedral core, resembling a rod. The formula of the Au(I) complex is determined to be [Au(2)(PPh(3))(2)(SC(2)H(4)Ph)](+) by electrospray ionization (ESI) mass spectrometry, and its crystal structure (with SbF(6)(-) counterion) reveals Au-Au bridged by -SC(2)H(4)Ph and with terminal bonds to two PPh(3) ligands. Unlike previously reported [Au(2)(PR(3))(2)(SC(2)H(4)Ph)](+) complexes in the solid state, which exist as tetranuclear complexes (i.e., dimers of [Au(2)(PR(3))(2)(SC(2)H(4)Ph)](+) units) through a Au···Au aurophilic interaction, in our case we found that the [Au(2)(PPh(3))(2)(SC(2)H(4)Ph)](+) complex exists as a single entity, rather than being dimerized to form a tetranuclear complex. The observation of this Au(I) complex allows us to gain insight into the intriguing conversion process from polydisperse Au nanoparticles to monodisperse Au(25) nanoclusters.

Isolation of ubiquitous Au(40)(SR)(24) clusters from the 8 kDa gold clusters.

We report chromatographic isolation of a new thiolate-protected gold cluster species from the approximately 8 kDa Au(n)(SR)(m) clusters. This new cluster is separated by size-exclusion chromatography from Au(38)(SC(2)H(4)Ph)(24) (a previously reported main component in the approximately 8 kDa gold-thiolate species). Based on detailed MALDI and ESI mass spectrometry analyses, the new cluster possesses a core mass of approximately 8.6 kDa and its formula is determined to be Au(40)(SC(2)H(4)Ph)(24). The Au(40)(SR)(24) species is also found to exist in other thiolate systems, including -SR=SC(6)H(13) and SC(5)H(11), indicating that Au(40)(SR)(24) is a ubiquitous cluster as is Au(38)(SR)(24).

Total structure determination of thiolate-protected Au38 nanoparticles.

We report the total structure of Au(38)(SC(2)H(4)Ph)(24) nanoparticles determined by single crystal X-ray crystallography. This nanoparticle is based upon a face-fused Au(23) biicosahedral core, which is further capped by three monomeric Au(SR)(2) staples at the waist of the Au(23) rod and six dimeric staples with three on the top icosahedron and other three on the bottom icosahedron. The six Au(2)(SR)(3) staples are arranged in a staggered configuration, and the Au(38)S(24) framework has a C(3) rotation axis.

An atomic-level strategy for unraveling gold nanocatalysis from the perspective of Au(n)(SR)m nanoclusters.

An atomic-level strategy is devised to gain insight into the origin of nanogold catalysis by using atomically monodisperse Au(n)(SR)(m) nanoclusters as well-defined catalysts for styrene oxidation. The Au(n)(SR)(m) nanoclusters are emerging as a new class of gold nanocatalyst to overcome the polydispersity of conventional nanoparticle catalysts. The unique atom-packing structure and electronic properties of Au(n)(SR)(m) nanoclusters (<2 nm) are rationalized to be responsible for their extraordinary catalytic activity observed in styrene oxidation. An interesting finding is that quantum size effects of Au(n)(SR)(m) nanoclusters, rather than the higher specific surface area, play a major role in gold-catalyzed selective oxidation of styrene. For example, Au(25)(SR)(18) nanoclusters (≈1 nm) are found to be particularly efficient in activating O(2), which is a key step in styrene oxidation, and hence, the ultrasmall Au(25) catalyst exhibits higher activity than do larger sizes. This atomic-level strategy has allowed us to obtain an important insight into some fundamental aspects of nanogold catalysis in styrene oxidation. The ultrasmall yet robust Au(n)(SR)(m) nanoclusters are particularly promising for studying the mechanistic aspects of nanogold catalysis and for future design of better catalysts with high activity and selectivity for certain chemical processes.

Controlling nanoparticles with atomic precision: the case of Au144(SCH2CH2Ph)60.

We report a facile, two-step synthetic method for preparing truly monodiserse Au(144)(SCH(2)CH(2)Ph)(60) nanoparticles with their formula determined by electrospray mass spectrometry in conjunction with other characterization. A remarkable advantage of our synthetic approach lies in that it solely produces Au(144)(SCH(2)CH(2)Ph)(60) nanoparticles, hence, eliminating nontrivial, postsynthetic steps of size separation, which has proven to be very difficult. This advantage makes the approach and the type of nanoparticles generated by it of broad utility for practical applications. Unlike their larger counterparts, Au nanocrystals (typically >2 nm) that are crystalline and show a prominent surface plasmon resonance band at approximately 520 nm (for spherical particles), the Au(144)(SCH(2)CH(2)Ph)(60) nanoparticles instead exhibit a stepwise, multiple-band absorption spectrum, indicating quantum confinement of electrons in the particle. In addition, these ultrasmall nanoparticles do not adopt face-centered cubic structure as in Au nanocrystals or bulk gold.

Thiolate-protected Au(20) clusters with a large energy gap of 2.1 eV.

We report a kinetically controlled approach to synthesizing thiolate-capped 20-atom gold clusters. ESI mass spectrometry analysis in combination with other methods, including elemental analysis, XPS, NMR, and thermogravimetric analysis, determines the cluster composition to be Au(20)(SCH(2)CH(2)Ph)(16). The Au(20)(SCH(2)CH(2)Ph)(16) clusters exhibit a stepwise, multiple-band optical absorption spectrum, reminiscent of quantum confinement behavior. The optical energy gap is determined to be E(g) approximately 2.15 eV; this HOMO-LUMO gap is remarkably larger than that of Au(25)(SR)(18) (1.3 eV). The Au(20)(SCH(2)CH(2)Ph)(16) clusters were also found to be particularly robust again excess thiol etching, in contrast to the previous report on the thiol etching stability of a series of glutathione-capped Au(n)(SG)(m) (n < 25) clusters. This stability difference might indicate some structural differences between Au(20)(SCH(2)CH(2)Ph)(16) and Au(n)(SG)(m) (n < 25). The crystal structure of the Au(20)(SCH(2)CH(2)Ph)(16) cluster remains to be unraveled in future work.

Reversible switching of magnetism in thiolate-protected Au25 superatoms.

We report reversible switching of paramagnetism in a well-defined gold nanoparticle system consisting of atomically monodisperse nanoparticles containing 25 gold atoms protected by 18 thiolates [abbreviated as Au(25)(SR)(18)]. The magnetism in these nanoparticles can be switched on or off by precisely controlling the charge state of the nanoparticle, that is, the magnetic state of the Au(25)(SR)(18) nanoparticles is charge-neutral while the nonmagnetic state is an anionic form of the particle. Electron paramagnetic resonance (EPR) spectroscopy measurements establish that the magnetic state of the Au(25)(SR)(18) nanoparticles possess one unpaired spin per particle. EPR studies also imply an unusual electronic structure of the Au(25)(SR)(18) nanoparticle. Density functional theory calculations coupled with the experiments successfully explain the origin of the observed magnetism in a Au(25)(SR)(18) nanoparticle as arising from one unpaired spin having distinct P-like character and delocalized among the icosahedral Au(13) core of the particle in the highest occupied molecular orbital. The results suggest that the Au(25)(SR)(18) nanoparticles are best considered as ligand-protected superatoms.