Innovative ochre processing and tool use in China 40,000 years ago.

Homo sapiens was present in northern Asia by around 40,000 years ago, having replaced archaic populations across Eurasia after episodes of earlier population expansions and interbreeding1-4. Cultural adaptations of the last Neanderthals, the Denisovans and the incoming populations of H. sapiens into Asia remain unknown1,5-7. Here we describe Xiamabei, a well-preserved, approximately 40,000-year-old archaeological site in northern China, which includes the earliest known ochre-processing feature in east Asia, a distinctive miniaturized lithic assemblage with bladelet-like tools bearing traces of hafting, and a bone tool. The cultural assembly of traits at Xiamabei is unique for Eastern Asia and does not correspond with those found at other archaeological site assemblages inhabited by archaic populations or those generally associated with the expansion of H. sapiens, such as the Initial Upper Palaeolithic8-10. The record of northern Asia supports a process of technological innovations and cultural diversification emerging in a period of hominin hybridization and admixture2,3,6,11.

Earliest Prepared core technology in Eurasia from Nihewan (China): Implications for early human abilities and dispersals in East Asia.

Organized flaking techniques to obtain predetermined stone tools have been traced back to the early Acheulean (also known as mode 2) in Africa and are seen as indicative of the emergence of advanced technical abilities and in-depth planning skills among early humans. Here, we report one of the earliest known examples of prepared core technology in the archaeological record, at the Cenjiawan (CJW) site in the Nihewan basin of China, dated 1.1 Mya. The operational schemes reconstructed from the CJW refit sets, together with shaping patterns observed in the retouched tools, suggest that Nihewan basin toolmakers had the technical abilities of mode 2 hominins, and developed different survival strategies to adapt to local raw materials and environments. This finding predates the previously earliest known prepared core technology from Eurasia by 0.3 My, and the earliest known mode 2 sites in East Asia by a similar amount of time, thus suggesting that hominins with advanced technologies may have migrated into high latitude East Asia as early as 1.1 Mya.

Application scenario-oriented molecule generation platform developed for drug discovery.

Design of molecules for candidate compound selection is one of the central challenges in drug discovery due to the complexity of chemical space and requirement of multi-parameter optimization. Here we present an application scenario-oriented platform (ID4Idea) for molecule generation in different scenarios of drug discovery. This platform utilizes both library or rule based and generative based algorithms (VAE, RNN, GAN, etc.), in combination with various AI learning types (pre-training, transfer learning, reinforcement learning, active learning, etc.) and input representations (1D SMILES, 2D graph, 3D shape, binding site, pharmacophore, etc.), to enable customized solutions for a given molecular design scenario. Besides the usual generation followed screening protocol, goal-directed molecule generation can also be conducted towards predefined goals, enhancing the efficiency of hit identification, lead finding, and lead optimization. We demonstrate the effectiveness of ID4Idea platform through case studies, showcasing customized solutions for different design tasks using various input information, such as binding pockets, pharmacophores, and compound representations. In addition, remaining challenges are discussed to unlock the full potential of AI models in drug discovery and pave the way for the development of novel therapeutics.

Low dinosaur biodiversity in central China 2 million years prior to the end-Cretaceous mass extinction.

Whether or not nonavian dinosaur biodiversity declined prior to the end-Cretaceous mass extinction remains controversial as the result of sampling biases in the fossil record, differences in the analytical approaches used, and the rarity of high-precision geochronological dating of dinosaur fossils. Using magnetostratigraphy, cyclostratigraphy, and biostratigraphy, we establish a high-resolution geochronological framework for the fossil-rich Late Cretaceous sedimentary sequence in the Shanyang Basin of central China. We have found only three dinosaurian eggshell taxa (Macroolithus yaotunensis, Elongatoolithus elongatus, and Stromatoolithus pinglingensis) representing two clades (Oviraptoridae and Hadrosauridae) in sediments deposited between ∼68.2 and ∼66.4 million y ago, indicating sustained low dinosaur biodiversity, and that assessment is consistent with the known skeletal remains in the Shanyang and surrounding basins of central China. Along with the dinosaur eggshell records from eastern and southern China, we find a decline in dinosaur biodiversity from the Campanian to the Maastrichtian. Our results support a long-term decline in global dinosaur biodiversity prior to 66 million y ago, which likely set the stage for the end-Cretaceous nonavian dinosaur mass extinction.

LiPF6 Induces Phosphorization of Garnet-Type Solid-State Electrolyte for Stable Lithium Metal Batteries.

Garnet solid electrolyte Li6.4 La3 Zr1.4 Ta0.6 O12 (LLZTO) is an excellent inorganic ceramic-type solid electrolyte; however, the presence of Li2 CO3 impurities on its surface hinders Li-ion transport and increases the interface impedance. In contrast to traditional methods of mechanical polishing, acid corrosion, and high-temperature reduction for removing Li2 CO3 , herein, a straightforward "waste-to-treasure" strategy is proposed to transform Li2 CO3 into Li3 PO4 and LiF in LiPF6 solution under 60 °C. It is found that the formation of Li3 PO4 during LLZTO pretreatment facilitates rapid Li-ion transport and enhances ionic conductivity, and the LLZTO/PAN composite polymer electrolyte shows the highest Li-ion transference number of 0.63. Additionally, the dense LiF layer serves to safeguard the internal garnet solid electrolyte against solvent decomposition-induced chemical adsorption. Symmetric Li/Li cells assembled with treated LLZTO/PAN composite electrolyte exhibit a critical current density of 1.1 mA cm-2 and a long lifespan of up to 700 h at a current density of 0.2 mA cm-2 . The Li/LiFePO4 solid-state cells demonstrate stable cycling performances for 141 mAh g-1 at 0.5 C, with capacity retention of 93.6% after 190 cycles. This work presents a novel approach to converting waste into valuable resources, offering the advantages of simple processes, and minimal side reactions.

Bipolar Polymeric Protective Layer for Dendrite-Free and Corrosion-Resistant Lithium Metal Anode in Ethylene Carbonate Electrolyte.

The unstable interface between Li metal and ethylene carbonate (EC)-based electrolytes triggers continuous side reactions and uncontrolled dendrite growth, significantly impacting the lifespan of Li metal batteries (LMBs). Herein, a bipolar polymeric protective layer (BPPL) is developed using cyanoethyl (-CH2CH2C≡N) and hydroxyl (-OH) polar groups, aiming to prevent EC-induced corrosion and facilitating rapid, uniform Li+ ion transport. Hydrogen-bonding interactions between -OH and EC facilitates the Li+ desolvation process and effectively traps free EC molecules, thereby eliminating parasitic reactions. Meanwhile, the -CH2CH2C≡N group anchors TFSI- anions through ion-dipole interactions, enhancing Li+ transport and eliminating concentration polarization, ultimately suppressing the growth of Li dendrite. This BPPL enabling Li|Li cell stable cycling over 750 cycles at 10 mA cm-2 for 2 mAh cm-2. The Li|LiNi0.8Mn0.1Co0.1O2 and Li|LiFePO4 full cells display superior electrochemical performance. The BPPL provides a practical strategy to enhanced stability and performance in LMBs application.

Multi-channel GCN ensembled machine learning model for molecular aqueous solubility prediction on a clean dataset.

This study constructed a new aqueous solubility dataset and a solubility regression model which was ensembled by GCN and machine learning models. Aqueous solubility is a key physiochemical property of small molecules in drug discovery. In the past few decades, there have been many studies about solubility prediction. However, many of these studies have high root mean squared error (RMSE). Meanwhile, their dataset always contains salt compounds and solubility data obtained from different experimental conditions. In this paper, we constructed a clean dataset with 2609 compounds, which was small but contains only solubility records without salts at the same temperatures (25 °C). Here, we applied graph convolutional neural network (GCN) to construct an aqueous solubility prediction model. To enhance the performance of the model, the molecular MACCS key fingerprints and physiochemical descriptors were also combined with the GCN model to build a multi-channel model. Additionally, the authors also built two machine learning models (support vector regression and gradient boost decision tree) and assembled them to the GCN model to improve the root mean squared error (RMSE = 0.665). Finally, comparative experiments have shown that our framework achieved the best performance on ESOL dataset (RMSEval = 0.56, RMSEtest = 0.44) and surpassed four established software on aqueous solubility prediction of new compounds.

The appearance and duration of the Jehol Biota: Constraint from SIMS U-Pb zircon dating for the Huajiying Formation in northern China.

The Lower Cretaceous Huajiying Formation of the Sichakou Basin in northern Hebei Province, northern China contains key vertebrate taxa of the early Jehol Biota, e.g., Protopteryx fengningensis, Archaeornithura meemannae, Peipiaosteus fengningensis, and Eoconfuciusornis zhengi This formation arguably documents the second-oldest bird-bearing horizon, producing the oldest fossil records of the two major Mesozoic avian groups Enantiornithes and Ornithuromorpha. Hence, precisely determining the depositional ages of the Huajiying Formation would advance our understanding of the evolutionary history of the Jehol Biota. Here we present secondary ion mass spectrometry (SIMS) U-Pb zircon analysis results of eight interbedded tuff/tuffaceous sandstone samples from the Huajiying Formation. Our findings, combined with previous radiometric dates, suggest that the oldest enantiornithine and ornithuromorph birds in the Jehol Biota are ∼129-131 Ma, and that the Jehol Biota most likely first appeared at ∼135 Ma. This expands the biota's temporal distribution from late Valanginian to middle Aptian with a time span of about 15 My.

Total Structure, Electronic Structure and Catalytic Hydrogenation Activity of Metal-Deficient Chiral Polyhydride Cu57 Nanoclusters.

Accurate identifying and in-depth understanding of the defect sites in a working nanomaterial could hinge on establishing specific defect-activity relationships. Yet, atomically precise coinage-metal nanoclusters (NCs) possessing surface vacancy defects are scarce primarily owing to challenges in the synthesis and isolation of such defective NCs. Herein we report a mixed-ligand strategy to synthesizing an intrinsically chiral and metal-deficient copper hydride-rich NC [Cu57 H20 (PET)36 (TPP)4 ]+ (Cu57 H20 ). Its total structure (including hydrides) and electronic structure are well established by combined experimental and computational results. Crystal structure reveals Cu57 H20 features a cube-like Cu8 kernel embedded in a corner-missing metal-ligand shell of Cu49 (PET)36 (TPP)4 . Single Cu vacancy defect site occurs at one corner of the shell, evocative of mono-lacunary polyoxometalates. Theoretical calculations demonstrate that the above-mentioned point vacancy causes one surface hydride exposed as an interfacial capping µ3 -H- , which is accessible in chemical reaction, as proved by deuterated experiment. Moreover, Cu57 H20 shows catalytic activity in the hydrogenation of nitroarene. The success of this work opens the way for the research on well-defined chiral metal-deficient Cu and other metal NCs, including exploring their application in asymmetrical catalysis.

Effective Reaction-Based De Novo Strategy for Kinase Targets: A Case Study on MERTK Inhibitors.

Reaction-based de novo design is the computational generation of novel molecular structures by linking building blocks using reaction vectors derived from chemistry knowledge. In this work, we first adopted a recurrent neural network (RNN) model to generate three groups of building blocks with different functional groups and then constructed an in silico target-focused combinatorial library based on chemical reaction rules. Mer tyrosine kinase (MERTK) was used as a study case. Combined with a scaffold enrichment analysis, 15 novel MERTK inhibitors covering four scaffolds were achieved. Among them, compound 5a obtained an IC50 value of 53.4 nM against MERTK without any further optimization. The efficiency of hit identification could be significantly improved by shrinking the compound library with the fragment iterative optimization strategy and enriching the dominant scaffold in the hinge region. We hope that this strategy can provide new insights for accelerating the drug discovery process.

Accurate calculation of absolute free energy of binding for SHP2 allosteric inhibitors using free energy perturbation.

Accurate prediction of binding affinity is a primary objective in structure-based drug discovery. A free energy perturbation (FEP) method based on molecular dynamics simulation shows great promise for protein-ligand binding affinity predictions. However, accurate calculation of binding affinity for allosteric inhibitors remains unknown and elusive, which hampers the discovery of allosteric inhibitors. Allosteric inhibitors exhibit several significant advantages over orthosteric inhibitors including higher specificity and lower side effects. Allosteric inhibitors against SHP2 are thought to be beneficial not only for diseases related to metabolism, but also for cancer, which make SHP2 a potential drug target. However, high structural sensitivity makes structural optimization of SHP2 allosteric inhibitors face challenges. Herein, we calculated the absolute binding free energy of SHP2 allosteric inhibitors using the FEP method by employing different λ-windows/simulation time sampling strategies. A simulation run with 32 λ-windows/64 ps sampling strategy delivered an excellent correlation (r = 0.96) and an unprecedented low mean absolute error of 0.5 kcal mol-1 between predicted binding free energies and experimental ones, outperforming the MM/PBSA method. Our study demonstrates the possibility to accurately calculate the absolute binding free energy of allosteric inhibitors using FEP, which offers exciting prospects for the discovery of more effective allosteric inhibitors.

Enhancing Interfacial Contact in Solid-State Batteries with a Gradient Composite Solid Electrolyte.

Solid-state batteries promise to meet the challenges of high energy density and high safety for future energy storage. However, poor interfacial contact and complex manufacturing processes limit their practical applications. Herein, a simple strategy is proposed to enhance interfacial contact by introducing a gradient composite polymer solid electrolyte (GCPE), which is prepared by a facile UV-curing polymerization technique. The high-Li6.4 La3 Zr1.4 Ta0.6 O12 (LLZTO)-content side of the electrolyte exhibits high oxidation resistance (5.4 V versus Li+ /Li), making it compatible with a high-voltage cathode material, whereas the LLZTO-deficient side achieves excellent interfacial contact with the Li metal anode, facilitating uniform Li deposition. Benefiting from the elaborate composition and structure of GCPE films, the symmetric Li//Li cell exhibits a low-voltage hysteresis potential of 42 mV and a long cycle life of >1900 h without short-circuiting. The Li//LiFePO4 solid-state batteries deliver a capacity of 161.0 mA h g-1 at 60 °C and 0.1 C (82.4% capacity is retained after 200 cycles). Even at 80 °C, the cell still shows an outstanding capacity of 132.9 mAh g-1 at 0.2 C after 100 cycles. The design principle of gradient electrolytes provides a new path for achieving enhanced interfacial contact in high-performance solid-state batteries.

Early Pleistocene hominin teeth from Meipu, southern China.

The rarity and poor preservation of hominin fossils from the East Asian Early Pleistocene hamper our understanding of their taxonomy and possible phylogenetic relationship with other members of the genus Homo. In the 1970s, four isolated hominin teeth were recovered from the Meipu site, southern China, which biostratigraphic analysis placed in the late Early Pleistocene. Early reports assigned the teeth to late Homo erectus. Since then, the teeth have not been re-evaluated, nor has reliable dating been performed at the Meipu site. Here, biostratigraphic and paleomagnetic dating allow for a more precise chronological constraint of the Meipu hominins in the late Early Pleistocene, between 780 ka and 990 ka, making them one of the few known hominins for this time in mainland Asia. The comparison of the morphology of the Meipu teeth with other members of the genus Homo reveals that the Meipu teeth preserve traits such as moderate shoveling of the I1, the square crown contour of M1, and a buccolingually wider lingual cusp in P4 that make them closer to early Homo specimens from Africa and Homo ergaster from Dmanisi (Georgia). In addition, the Meipu teeth exhibit features that are more typical for late mainland East Asian H. erectus, such as the moderately convex I1 labial surface and a pronouncedly convex I2 labial surface. In these features, the Meipu hominins are morphologically intermediate between African/Dmanisi early Homo and East Asian Middle Pleistocene hominins. This study contributes to a better understanding of the morphologies and the taxonomic status of East Asian Early Pleistocene hominins, a time period for which the hominin evidence with secure stratigraphic context is scarce.

Mesopithecus pentelicus from Zhaotong, China, the easternmost representative of a widespread Miocene cercopithecoid species.

A dentate mandible and proximal femur of Mesopithecus pentelicusWagner, 1839 are described from the Shuitangba lignite mine in Zhaotong Prefecture, northeastern Yunnan Province, China. The remains were retrieved from sediments just below those that yielded a juvenile Lufengpithecus cranium and are dated at about ∼6.4 Ma. The mandible and proximal femur were found in close proximity and are probably of the same individual. The lower teeth are metrically and morphologically closely comparable with those of confirmed M. pentelicus from Europe, and on this basis, the specimen is assigned to this species. The anatomy of the proximal femur indicates that the Shuitangba Mesopithecus was a semiterrestrial quadruped that engaged in a range of mostly arboreal activities, including walking, climbing, and occasional leaping, with an abducted hip joint. The Shuitangba Mesopithecus is dentally typical for the genus but may have been more arboreal than previously described for M. pentelicus. M. pentelicus is well known from late Miocene (MN 11-12) sites in Europe and southwest Asia. Its estimated average rate of dispersal eastward was relatively slow, although it could have been episodically more rapid. The presence of a colobine, only slightly lower in the same section at Shuitangba that produced Lufengpithecus, is one of the only two well-documented instances of the near or actual co-occurrence of a monkey and ape in the Miocene of Eurasia. At Shuitangba, M. pentelicus occupied a freshwater-margin habitat with beavers, giant otters, swamp rabbits, and many aquatic birds. The presence of M. pentelicus in southwest China near the end of the Miocene further attests to the ecological versatility of a species long recognized as widespread and adaptable. The modern colobines of Asia, some or all of which are probable descendants of Mesopithecus, have gone on to inhabit some of the most highly seasonal and extreme habitats occupied by nonhuman primates.

Oldest colobine calcaneus from East Asia (Zhaotong, Yunnan, China).

Apart from a juvenile hominoid, the locality of Shuitangba (southwestern China, 6.5-6.0 Ma) has yielded a mandible and proximal femur attributed to the colobine genus Mesopithecus. A complete colobine calcaneus also accompanies this material, but its association with the other Mesopithecus material remains to be confirmed. These fossil elements are very important as they represent the oldest known colobines from East Asia, extend the dispersal of Mesopithecus to southwestern China, and underscore its close affinities and potential ancestry to the odd-nosed colobines. The present article focuses on the functional morphology of this complete calcaneus to reconstruct the positional habits, infer the paleocology, and understand the dispersal patterns of this fossil colobine. The studied characters corroborate the attribution of this element to colobines and support potential affinities with the Mesopithecus remains of the same locality. Functionally, characters such as the long and narrow tuber calcanei, the short proximal calcaneal region, and the relatively extended and long and narrow proximal calcaneoastragalar facet appear to enable habitual pedal flexion with conjunct inversion that accommodate the foot on diversely oriented and differently sized arboreal substrates. On the other hand, the relatively short distal calcaneal region is functionally related to (mainly terrestrial) quadrupedal activities, wherein thrust and rapid flexion are required. This combination of characters suggests that the Shuitangba colobine could move at ease on arboreal substrates and was also able to occasionally use terrestrial substrates. The potential affinities of this calcaneus to Mesopithecus and its positional profile most likely imply an eastward migration via forested corridors. In Shuitangba, this fossil colobine could trophically and positionally exploit a wide range of habitats successfully coexisting with resident hominoids.

Discovery of Dual FGFR4 and EGFR Inhibitors by Machine Learning and Biological Evaluation.

Kinase inhibitors are widely used in antitumor research, but there are still many problems such as drug resistance and off-target toxicity. A more suitable solution is to design a multitarget inhibitor with certain selectivity. Herein, computational and experimental studies were applied to the discovery of dual inhibitors against FGFR4 and EGFR. A quantitative structure-property relationship (QSPR) study was carried out to predict the FGFR4 and EGFR activity of a data set consisting of 843 and 5088 compounds, respectively. Four different machine learning methods including support vector machine (SVM), random forest (RF), gradient boost regression tree (GBRT), and XGBoost (XGB) were built using the most suitable features selected by the mutual information algorithm. As for FGFR4 and EGFR, SVM showed the best performance with R2test-FGFR4 = 0.80 and R2test-EGFR = 0.75, demonstrating excellent model stability, which was used to predict the activity of some compounds from an in-house database. Finally, compound 1 was selected, which exhibits inhibitory activity against FGFR4 (IC50 = 86.2 nM) and EGFR (IC50 = 83.9 nM) kinase, respectively. Furthermore, molecular docking and molecular dynamics simulations were performed to identify key amino acids for the interaction of compound 1 with FGFR4 and EGFR. In this paper, the machine-learning-based QSAR models were established and effectively applied to the discovery of dual-target inhibitors against FGFR4 and EGFR, demonstrating the great potential of machine learning strategies in dual inhibitor discovery.

In Silico Design and Analysis of a Kinase-Focused Combinatorial Library Considering Diversity and Quality.

A structurally diverse, high-quality, and kinase-focused database plays a critical role in finding hits or leads in kinase drug discovery. Here, we propose a workflow for designing a virtual kinase-focused combinatorial library using existing structures. Based on the analysis of known protein kinase inhibitors (PKIs), detailed fragment optimization, fragment selection, fragment linking, and a molecular filtering scheme were defined. Quick recognition of core fragments that can possibly form dual hydrogen bonds with the hinge region of the ATP-pocket was proposed. Furthermore, three diversity and four quality metrics were chosen for compound library analysis, which can be applied to databases with over 30 million structures. Compared with 13 commercial libraries, our protocol demonstrates a special advantage in terms of good skeleton diversity, acceptable fingerprint diversity, balanced scaffold distribution, and high quality, which can work well not only on existing PKIs, but also on four chosen commercial libraries. Overall, the strategy can greatly facilitate the expansion of a desirable chemical space for kinase drug discovery.

The Paleolithic in the Nihewan Basin, China: Evolutionary history of an Early to Late Pleistocene record in Eastern Asia.

The Nihewan Basin of China preserves one of the most important successions of Paleolithic archeological sites in Eurasia. Stratified archeological sites and mammalian fossils, first reported in the 1920s, continue to be recovered in large-scale excavation projects. Here, we review key findings from archeological excavations in the Nihewan Basin ranging from ~1.66 Ma to 11.7 ka. We place particular emphasis on changes in stone tool technology over the long term. Though Pleistocene lithic industries from East Asia are often described as simple in character, re-evaluation of the stone tool evidence from the Nihewan Basin demonstrates significant, though periodic, innovations and variability in manufacturing techniques through time, indicating adaptive and technological flexibility on the part of hominins. Synthesis of paleoenvironmental and archeological data indicate changes in hominin occupation frequency in the Nihewan Basin, with chronological gaps suggesting that continuous presence in high, seasonal latitudes was not possible prior to the Late Pleistocene.

Archaeointensity results spanning the past 6 kiloyears from eastern China and implications for extreme behaviors of the geomagnetic field.

Variations of the Earth's geomagnetic field during the Holocene are important for understanding centennial to millennial-scale processes of the Earth's deep interior and have enormous potential implications for chronological correlations (e.g., comparisons between different sedimentary recording sequences, archaeomagnetic dating). Here, we present 21 robust archaeointensity data points from eastern China spanning the past ∼6 kyr. These results add significantly to the published data both regionally and globally. Taking together, we establish an archaeointensity reference curve for Eastern Asia, which can be used for archaeomagnetic dating in this region. Virtual axial dipole moments (VADMs) of the data range from a Holocene-wide low of ∼27 to "spike" values of ∼166 ZAm2 (Z: 1021). The results, in conjunction with our recently published data, confirm the existence of a decrease in paleointensity (DIP) in China around ∼2200 BCE. These low intensities are the lowest ever found for the Holocene and have not been reported outside of China. We also report a spike intensity of 165.8 ± 6.0 ZAm2 at ∼1300 BCE (±300 y), which is either a prelude to or the same event (within age uncertainties) as spikes first reported in the Levant.

A Sodalite-Type Silver Orthophosphate Cluster in a Globular Silver Nanocluster.

The synthesis and structure of a giant 102-silver-atom nanocluster (NC) 1 is presented. X-ray structural analysis reveals that 1 features a multi-shelled metallic core of Ag6 @Ag24 @Ag60 @Ag12 . An octahedral Ag6 core is encaged by a truncated octahedral Ag24 shell. The Ag24 shell is composed of a hitherto unknown sodalite-type silver orthophosphate cluster (SOC) {(Ag3 PO4 )8 }, reminiscent of the Ag3 PO4 photocatalyst. The SOC is capped by six interstitial sulfur atoms, giving a unique anionic cluster [Ag6 @{(Ag3 PO4 )8 }S6 ]6- , which functions as an intricate polyhedral template with abundant surface O and S atoms guiding the formation of a rare rhombicosidodecahedral Ag60 shell. An array of 6 linear Ag2 staples further surround this Ag60 shell. [Ag6 @{(Ag3 PO4 )8 }S6 ]6- is an unusual Ag-based templating anion to induce the assembly of a SOC within silver NC. This finding provides molecular models for bulk Ag3 PO4 , and offers a fresh template strategy for the synthesis of silver NCs with high symmetry.