Strong Ligand Control for Noble Metal Nanostructures.

ConspectusNanosynthesis is the art of creating nanostructures, with on-demand synthesis as the ultimate goal. Noble metal nanoparticles have wide applications, but the available synthetic methods are still limited, often giving nanospheres and symmetrical nanocrystals. The fundamental reason is that the conventional weak ligands are too labile to influence the materials deposition, so the equivalent facets always grow equivalently. Considering that the ligands are the main synthetic handles in colloidal synthesis, our group has been exploring strong ligands for new growth modes, giving a variety of sophisticated nanostructures. The model studies often involve metal deposition on seeds functionalized with a certain strong ligand, so that the uneven distribution of the surface ligands could guide the subsequent deposition.In this Account, we focus on the design principles underlying the new growth modes, summarizing our efforts in this area along with relevant literature works. The basics of ligand control are first revisited. Then, the four major growth modes are summarized as follows: (1) The curvature effects would divert the materials deposition away from the high-curvature tips when the ligands are insufficient. With ligands fully covering the seeds, the sparser ligand packing at the tips would then promote the initial nucleation thereon. (2) The strong ligands may get trapped under the incoming metal layer, thus modulating the interfacial energy of the core-shell interface. The evidence for embedded ligands is discussed, along with examples of Janus nanostructures arising from the synthetic control, including metal-metal, metal-semiconductor, and metal-C60 systems using a variety of ligands. (3) Active surface growth is an unusual mode with divergent growth rates, so that part of the emerging surface is inhibited, and the growth is focused onto a few active sites. With seeds attached to oxide substrates, the selective deposition at the metal-substrate interface produces ultrathin nanowires. The synthesis can be generally applied to grow Au, Ag, Pd, Pt, and hybrid nanowires, with straight, spiral, or helical structures, and even rapid alteration of segments via electrochemical methods. In contrast, active surface growth for colloidal nanoparticles has to be more carefully controlled. The rich growth phenomena are discussed, highlighting the role of strong ligands, the control of deposition rates, the chiral induction, and the evidence for the active sites. (4) An active site with sparse ligands could also be exploited in etching, where the freshly exposed surface would promote further etching. The result is an unusual sharpening etching mode, in contrast to the conventional rounding mode for minimized surface energy.Colloidal nanosynthesis holds great promise for scalable on-demand synthesis, providing the crucial nanomaterials for future explorations. The strong ligands have delivered powerful synthetic controls, which could be further enhanced with in-depth studies on growth mechanisms and synthetic strategies, as well as functions and properties.

Modulating the Charge Transfer Plasmon in Bridged Au Core-Satellite Homometallic Nanostructures.

The localized surface plasmon resonance (LSPR) is one of the important properties for noble metal nanoparticles. Tuning the LSPR on demand thus has attracted tremendous interest. Beyond the size and shape control, manipulating intraparticle coupling is an effective way to tailor their LSPR. The charge transfer plasmon (CTP) is the most important mode of conductive coupling between subunits linked by conductive bridges that are well studied for structures prepared on substrates by lithography method. However, the colloidal synthesis of CTP structure remains a great challenge. This work reports the colloidal synthesis of extraordinary bridged Au core-satellite structures by exploiting the buffer effect of polydopamine shell on Au core for Au atom diffusion, in which the Au bridge is well controlled in terms of width and length. Benefiting from the tunable Au bridges, the resonance energy of the CTP can be readily controlled. As a result, the LSPR absorptions of the core-satellite structures are continuously tuned within the NIR spectral range (from 900 to >1300 nm), demonstrating their great potentials for ultrafast nano-optics and biomedical applications.

Engineering the Au-Cu2 O Crystalline Interfaces for Structural and Catalytic Integration.

Precise structural control has attracted tremendous interest in pursuit of the tailoring of physical properties. Here, this work shows that through strong ligand-mediated interfacial energy control, Au-Cu2 O dumbbell structures where both the Au nanorod (AuNR) and the partially encapsulating Cu2 O domains are highly crystalline. The synthetic advance allows physical separation of the Au and Cu2 O domains, in addition to the use of long nanorods with tunable absorption wavelength, and the crystalline Cu2 O domain with well-defined facets. The interplay of plasmon and Schottky effects boosts the photocatalytic performance in the model photodegradation of methyl orange, showing superior catalytic efficiency than the AuNR@Cu2 O core-shell structures. In addition, compared to the typical core-shell structures, the AuNR-Cu2 O dumbbells can effectively electrochemically catalyze the CO2 to C2+ products (ethanol and ethylene) via a cascade reaction pathway. The excellent dual function of both photo- and electrocatalysis can be attributed to the fine physical separation of the crystalline Au and Cu2 O domains.

Facile Synthesis of Pd and PdPtNi Trimetallic Nanosheets as Enhanced Oxygen Reduction Electrocatalysts.

While bimetallic 2D metallic nanomaterials are widely synthesized and used as electrocatalysts with enhanced performance, trimetallic 2D structures are less commonly reported. In this work, a facile wet chemical method for synthesizing Pd nanosheets and PdPtNi trimetallic alloy nanosheets is developed. Without the introduction of gaseous CO and pressurized equipment, Pd nanosheets with a thickness of ≈2.85 nm and sizes in the range of 1-2 µm can be obtained. The facile synthesis conditions allow for a comprehensive study of the nanosheet growth mechanism. It is found that 2D growth is closely related to the product of solvent decomposition and the additive ligand diethylenetriamine. Further, by depositing Pt and Ni onto the Pd nanosheets, trimetallic nanosheets with tunable compositions can be obtained and applied as oxygen reduction reaction electrocatalysts. Typically, the Pd9 Pt1 Ni1 nanosheets have the highest half-wave potential of 0.928 V (vs reversible hydrogen electrode), which is 34 mV higher than that of commercial Pt/C and 28 mV higher than that of Pd/C, and also have high durability.

High fibrinogen-albumin ratio index (FARI) predicts poor survival in head and neck squamous cell carcinoma patients treated with surgical resection.

PURPOSE: The aim of the present study was to investigate the predictive value of the fibrinogen/albumin ratio index (FARI), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) on the prognosis of patients with operable head and neck squamous cell carcinoma (HNSCC). METHODS: A cohort of 155 operable HNSCC patients were enrolled. Laboratory and clinical data were extracted from the patients' electronic medical record. The optimal cut-off values were determined by receiver operating characteristic (ROC) curves analysis. Clinicopathological characteristics of patients were compared via Chi-square test. Survival curves were analyzed by Kaplan-Meier method. The prognostic factors were evaluated by univariate and multivariate analyses via the Cox hazards regression analysis. RESULTS: The median follow-up time was 31.7 months. An increased level of NLR was associated with later T stages, later N stages, and more advanced clinical stages(all P < 0.05). On univariate analyses, FARI, NLR, PLR, and N stage were correlated with progression-free survival (PFS) (all P < 0.05) as well as overall survival (OS) (all P < 0.05). And the clinical stage was only relevant to OS (P = 0.007). Multivariate Cox regression analysis revealed that FARI (HR 3.486, 95% CI 2.086-5.825, P < 0.001; HR 4.474, 95% CI 2.442-8.199, P < 0.001), NLR (HR 3.163, 95% CI 1.810-5.528, P < 0.001; HR 3.690, 95% CI 1.955-6.963, P < 0.001), and N stage (HR 1.718, 95% CI 1.058-2.789, P = 0.029; HR 1.777, 95% CI 1.024-3.084, P = 0.041) were independent prognostic factors for PFS and OS. CONCLUSION: Our findings indicate that FARI and NLR are effective and convenient markers for predicting prognosis in operable HNSCC patients.

Extracellular vesicles-encapsulated let-7i shed from bone mesenchymal stem cells suppress lung cancer via KDM3A/DCLK1/FXYD3 axis.

Accumulating evidence has suggested that extracellular vesicles (EVs) play a crucial role in lung cancer treatment. Thus, we aimed to investigate the modulatory role of bone marrow mesenchymal stem cell (BMSC)-EV-derived let-7i and their molecular mechanism in lung cancer progression. Microarray-based analysis was applied to predict lung cancer-related miRNAs and their downstream genes. RT-qPCR and Western blot analyses were conducted to determine Let-7i, lysine demethylase 3A (KDM3A), doublecortin-like kinase 1 (DCLK1) and FXYD domain-containing ion transport regulator 3 (FXYD3) expressions, after which dual-luciferase reporter gene assay and ChIP assay were used to identify the relationship among them. After loss- and gain-of-function assays, the effects of let-7i, KDM3A, DCLK1 and FXYD3 on the biological characteristics of lung cancer cells were assessed. Finally, tumour growth in nude mice was assessed by xenograft tumours in nude mice. Bioinformatics analysis screened out the let-7i and its downstream gene, that is KDM3A. The findings showed the presence of a high expression of KDM3A and DCLK1 and reduced expression of let-7i and FXYD3 in lung cancer. KDM3A elevated DCLK1 by removing the methylation of H3K9me2. Moreover, DCLK1 suppressed the FXYD3 expression. BMSC-EV-derived let-7i resulted in the down-regulation of KDM3A expression and reversed its promoting role in lung cancer development. Consistently, in vivo experiments in nude mice also confirmed that tumour growth was suppressed by the BMSC-EV-derived let-7i. In conclusion, our findings demonstrated that the BMSC-EV-derived let-7i possesses an inhibitory role in lung cancer progression through the KDM3A/DCLK1/FXYD3 axis, suggesting a new molecular target for lung cancer treatment.

Precise Dimerization of Hollow Fullerene Compartments.

Controlled docking, merging, and welding of hollow structures at the nanoscale are essential in constructing sophisticated hollow systems in ways similar to plumbing and biosystems. To this end, regioselectivity is an important milestone demanding new tools. We bring the steric effect, a powerful regioselective method in organic reactions, to the nanoscale. By tuning the exposed liquid area of Janus nanobowls, the sterics of the merging m-xylene liquid template can be precisely modulated, giving high-purity dimers (93.6%) and tetramers (80.6%) in one step. The shape uniformity of the nanobowls, the precise percentage of the exposed liquid, and, most importantly, the error correction in merging liquid domains are the critical factors leading to the precise regioselectivity. We believe that the development of a new regioselective tool and the understanding in docking and welding hollow structures would expand the horizon of nanoscience, opening new possibilities for designing sophisticated nanosystems.

Ultrafast acoustic vibrations of Au-Ag nanoparticles with varying elongated structures.

Acoustic vibrations of Au and Ag elongated nano-objects with original morphologies, from Ag-Ag homodimers to Au@Ag-Ag heterodimers and Au@Ag eccentric core-shell spheroids, have been experimentally investigated by ultrafast time-resolved optical spectroscopy. Their frequencies, obtained by the analysis of time-dependent transient absorption changes, are compared with the results obtained from finite element modeling (FEM) numerical computations, which allow assignment of the detected oscillating signals to fundamental radial and extensional modes. FEM was further used to analyze the effects of morphology and composition on the vibrational dynamics. FEM computations indicate that (1) the central distance between particles forming the nanodimers has profound effects on the extensional mode frequencies and a negligible influence on the radial mode ones, in analogy with the case of monometallic nanorods, (2) coating Au with Ag also has a strong mass-loading-like effect on the dimer and core-shell stretching mode frequency, while (3) its influence on the radial breathing mode is smaller and analogous to the non-monotonic frequency dependence on the Au fraction previously observed in isotropic bimetallic spheres. These findings are significant for developing a predictive understanding of nanostructure mechanical properties and for designing new mechanical nanoresonators.

Fine-Tuning the Homometallic Interface of Au-on-Au Nanorods and Their Photothermal Therapy in the NIR-II Window.

The localized surface plasmon resonance (LSPR) of plasmonic nanomaterials is highly dependent on their structures. Going beyond simple shape and size, further structural diversification demands the growth of non-wetting domains. Now, two new dimensions of synthetic controls in Au-on-Au homometallic nanohybrids are presented: the number of the Au islands and the emerging shapes. By controlling the interfacial energy and growth kinetics, a series of Au-on-AuNR hybrid structures are successfully obtained, with the newly grown Au domains being sphere and branched wire (nanocoral). The structural variety allowed the LSPR to be fine-tuned in full spectrum range, making them excellent candidates for plasmonic applications. The nanocorals exhibit black-body absorption and outstanding photothermal conversion capability in NIR-II window. In vitro and in vivo experiments verified them as excellent photothermal therapy and photoacoustic imaging agents.

Continuous Tuning of Au-Cu2 O Janus Nanostructures for Efficient Charge Separation.

In photocatalysis, the Schottky barrier in metal-semiconductor hybrids is known to promote charge separation, but a core-shell structure always leads to a charge build-up and eventually shuts off the photocurrent. Here, we show that Au-Cu2 O hybrid nanostructures can be continuously tuned, particularly when the Cu2 O domains are single-crystalline. This is in contrast to the conventional systems, where the hybrid configuration is mainly determined by the choice of materials. The distal separation of the Au-Cu2 O domains in Janus nanostructures leads to enhanced charge separation and a large improvement of the photocurrent. The activity of the Au-Cu2 O Janus structures is 5 times higher than that of the core-shell structure, and 10 times higher than that of the neat Cu2 O nanocubes. The continuous structural tuning allows to study the structure-property relationship and an optimization of the photocatalytic performance.

Investigation of expressions of PDK1, PLK1 and c-Myc in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Because the prognosis of DLBCL patients varies considerably, there is an urgent need to identify novel prognostic factors. In this study, we investigated the expression levels of the signalling enzyme 3-phosphoinositide-dependent protein kinase-1 (PDK1), the cell cycle regulatory enzyme Polo-like kinase 1 (PLK1) and the transcription factor (c-Myc) in DLBCL tissues and evaluated their clinical and prognostic significance. PDK1, PLK1 and c-Myc were detected by immunohistochemical staining of paraffin-embedded specimens from 152 DLBCL and 48 lymphadenitis patients. Expression levels were correlated with clinicopathological factors. PDK1, PLK1 and c-Myc were more commonly expressed in DLBCL specimens than in lymphadenitis specimens, and the expression of each protein correlated positively with that of the other two molecules. High PDK1, PLK1 and c-Myc expression, high international prognostic index score, high lactate dehydrogenase levels and late Ann Arbor stage were shown to correlate with shorter overall survival time. A multivariate Cox regression model showed that high expression levels of PLK1 and c-Myc were independent prognostic factors for DLBCL. Our findings indicate that PLK1 and c-Myc expression might be promising predictive biomarkers for DLBCL patients.

Construction of Long Narrow Gaps in Ag Nanoplates.

Hexagonal Ag nanoplates with long and ultranarrow gaps (about 90 nm in length, 2 nm in width) are synthesized via seed-mediated growth method. By growing around the polymer shell on the seed, the Ag domain cannot merge at the meet-up point, leaving a long narrow gap in the resulting plate. These gapped nanoplates exhibit high sensitivity in SERS detection, with limitation of 10-9 M for 2-naphthalenethiol.

STAT3 mediates multidrug resistance of Burkitt lymphoma cells by promoting antioxidant feedback.

Burkitt lymphoma (BL) is a highly aggressive B-cell neoplasm. Although BL is relatively sensitive to chemotherapy, some patients do not respond to initial therapy or relapse after standard therapy, which leads to poor prognosis. The mechanisms underlying BL chemoresistance remain poorly defined. Here, we report a mechanism for the relationship between the phosphorylation of STAT3 on Tyr705 and BL chemoresistance. In chemoresistant BL cells, STAT3 was activated and phosphorylated on Tyr705 in response to the generation of the reactive oxygen species (ROS), which induced Src Tyr416 phosphorylation after multi-chemotherapeutics treatment. As a transcription factor, the elevated phosphorylation level of STAT3Y705 increased the expression of GPx1 and SOD2, both of which protected cells against oxidative damage. Our findings revealed that the ROS-Src-STAT3-antioxidation pathway mediated negative feedback inhibition of apoptosis induced by chemotherapy. Thus, the phosphorylation of STAT3 on Tyr705 might be a target for the chemo-sensitization of BL.

Nanoscrews: Asymmetrical Etching of Silver Nanowires.

World's smallest screws with helical threads are synthesized via mild etching of Ag nanowires. With detailed characterization, we show that this nanostructure arises not from the transformation of the initial lattice, but the result of a unique etching mode. Three-dimensional printed models are used to illustrate the evolution of etch pits, from which a possible mechanism is postulated.

Achieving Site-Specificity in Multistep Colloidal Synthesis.

We show that partial inhibition of the emerging Ag domain can be achieved by controlling the growth dynamics. With the symmetry broken by the "fresh" surface, sequentially growth gives (Au sphere)-(Ag wire)-(Ag plate) triblock nanostructures. This new understanding opens doors to sophisticated synthetic designs, broadening the horizon of our search for functional architectures.

Exploiting core-shell synergy for nanosynthesis and mechanistic investigation.

The core-shell nanoparticle structure, which consists of an inner layer "guest" nanoparticle encapsulated inside another of a different material, is the simplest motif in two-component systems. In comparison to the conventional single-component systems, complex systems pose both challenges and opportunities. In this Account, we describe our recent progresses in using core-shell motif for exploring new and sophisticated nanostructures. Our discussion is focused on the mechanistic details, in order to facilitate rational design in future studies. We believe that systematic development of synthetic capability, particularly in complex and multifunctional systems, is of great importance for future applications. A key issue in obtaining core-shell nanostructures is minimizing the core-shell interfacial tension. Typically, one can coat the core with a ligand for better interaction with the shell. By selecting suitable ligands, we have developed general encapsulation methods in three systems. A variety of nanoparticles and nanowires were encapsulated using either amphiphilic block copolymer (polystyrene-block-poly(acrylic acid)), conductive polymer (polyaniline, polypyrrole, or polythiophene), or silica as the shell material. Obvious uses of shells are to stabilize colloidal objects, retain their surface ligands, prevent particle aggregation, or preserve the assembled superstructures. These simple capabilities are essential in our synthesis of surface-enhanced Raman scattering nanoprobes, in assigning the solution state of nanostructures before drying, and in developing purification methods for nano-objects. When it is applied in situ during nanocrystal growth or nanoparticle assembly, the intermediates trapped by shell encapsulation can offer great insights into the mechanistic details. On the other hand, having a shell as a second component provides a window for exploring the core-shell synergistic effects. Hybrid core-shell nanocrystals have interesting effects, for example, in causing the untwisting of nanowires to give double helices. In addition, partial polymer shells can bias nanocrystal growth towards one direction or promote the random growth of Au dendritic structures; contracting polymer shells can compress the embedded nanofilaments (Au nanowires or carbon nanotubes), forcing them to coil into rings. Also, by exploiting the sphere-to-cylinder conversion of block copolymer micelles, the Au nanoparticles pre-embedded in the polymer micelles can be assembled into long chains. Lastly, shells are also very useful for mechanistic studies. We have demonstrated such applications in studying the controlled aggregation of nanoparticles, in probing the diffusion kinetics of model drug molecules from nanocarriers to nanoacceptors, and in measuring the ionic diffusion through polyaniline shells.

Comparison of the efficacy of Oxford unicondylar replacement for the treatment of spontaneous osteonecrosis of the knee versus medial knee osteoarthritis: a meta-analysis.

OBJECTIVE: Meta-analysis of the comparative efficacy of Oxford unicompartmental knee arthroplasty (OUKA) for the treatment of spontaneous osteonecrosis of the knee (SONK) and medial knee osteoarthritis (MKOA). METHODS: A computerized search was conducted for literature related to OUKA treatments of SONK and MKOA across various databases, including the China National Knowledge Infrastructure, WAN FANG, VIP, SinoMed, Cochrane Library, PubMed, Embase, and Web of Science, covering the period from each database's inception to September 2023. Literature screening, quality assessment and data extraction were performed according to the inclusion and exclusion criteria. After extracting the literature data, RevMan 5.4 software was applied to analyse the postoperative knee function score, postoperative knee mobility, postoperative pain, bearing dislocation rate, aseptic loosening, postoperative progression of posterolateral arthritis, and revision rate. RESULT: A total of 9 studies were included, including 6 cohort studies and 3 matched case‒control studies. A total of 1544 knees were included, including 183 in the SONK group and 1361 in the MKOA group. The meta-analysis results showed that the SONK and MKOA groups showed a significant difference in postoperative knee function scores [MD = 0.16, 95% CI (- 1.20, 1.51), P = 0.82], postoperative knee mobility [MD = - 0.05, 95% CI (- 1.99. 1.89), P = 0.96], postoperative pain [OR = 0.89, 95% CI (0.23, 3.45), P = 0.87], rate of bearing dislocation [OR = 1.28, 95% CI (0.34, 4.81), P = 0.71], aseptic loosening [OR = 2.22, 95% CI (0.56, 8.82), P = 0.26], postoperative posterolateral arthritis progression [OR = 2.14, 95% CI (0.47, 9.86), P = 0.33], and revision rate [OR = 1.28, 95% CI (0.53, 3.04), P = 0.58] were not statistically significant. CONCLUSION: OUKA treatment with SONK and MKOA can achieve similar satisfactory clinical results.

Nomograms based on the lymphocyte-albumin-neutrophil ratio (LANR) for predicting the prognosis of nasopharyngeal carcinoma patients after definitive radiotherapy.

Much evidence has accumulated to show that inflammation and nutritional status are associated with the prognosis of patients with various cancers. The present study was designed to explore the prognostic role of the LANR in NPC patients receiving definitive radiotherapy and to construct a nomogram for predicting patient survival. This study retrospectively reviewed 805 NPC patients (604 in the training cohort and 201 in the validation cohort) who received definitive radiotherapy between January 2013 and December 2019. The clinical data and pretreatment laboratory test data, including lymphocyte count, neutrophil count, and serum ALB concentration, were collected for all patients. The LANR was calculated as the albumin × lymphocyte/neutrophil ratio. Patients in the training cohort and validation cohort were categorized into high-LANR and low-LANR groups according to the corresponding cutoff values. The independent prognostic factors for overall survival (OS), progression-free survival (PFS), relapse-free survival (RFS), and metastasis-free survival (MFS) were evaluated by univariate and multivariate Cox regression analyses, and a nomogram was subsequently constructed. The performance of the nomogram was evaluated by the concordance index (C-index) and calibration curve. A low LANR (< 14.3) was independently associated with worse OS, PFS and MFS in NPC patients. A prognostic prediction nomogram was established based on T stage, N stage, Eastern Cooperative Oncology Group (ECOG) score, treatment modality, and LANR and was validated. The C-indices of the nomograms for OS and PFS in the training cohort were 0.729 and 0.72, respectively. The C-indices of the nomograms for OS and PFS in the validation cohort were 0.694 and 0.695, respectively. The calibration curve revealed good consistency between the actual survival and the nomogram prediction. Patients with NPC with low pretreatment LANR had a poor prognosis. The nomogram established on the basis of the LANR was efficient and clinically useful for predicting survival in NPC patients who underwent definitive radiotherapy.

Predicting the overall survival and progression-free survival of nasopharyngeal carcinoma patients based on hemoglobin, albumin, and globulin ratio and classical clinicopathological parameters.

BACKGROUND: Serum biomarkers have a significant impact on the prediction of treatment outcomes in patients diagnosed with nasopharyngeal carcinoma (NPC). The primary aim of this study was to develop and validate a nomogram that incorporates hemoglobin, albumin, and globulin ratio (HAGR) and clinical data to accurately forecast treatment outcomes in patients with NPC. METHODS: A total of 796 patients diagnosed with NPC were included in the study. RESULTS: The results of the multivariate Cox analysis revealed that TNM stage and HAGR were found to be significant independent prognostic factors for OS and PFS. Furthermore, the utilization of the nomogram demonstrated a significant improvement in the evaluation of OS, PFS compared with the eighth TNM staging system. Additionally, the implementation of Kaplan-Meier curves and decision curve analysis curves further confirmed the discriminability and clinical effectiveness of the nomogram. CONCLUSIONS: The HAGR, an innovative prognostic factor grounded in the realm of immunonutrition, has emerged as a promising prognostic marker for both OS and PFS in individuals afflicted with NPC.