Integrated Anchored Stapling and Hierarchical Dynamics: MSICDA-Driven CREBBP Bromodomain Inhibition.

Despite recent success in the computational approaches of cyclic peptide design, current studies face challenges in modeling noncanonical amino acids and nonstandard cyclizations due to limited data. To address this challenge, we developed an integrated framework for the tailored design of stapled peptides (SPs) targeting the bromodomain of CREBBP (CREBBP-BrD). We introduce a powerful combination of anchored stapling and hierarchical molecular dynamics to design and optimize SPs by employing the MultiScale integrative conformational dynamics assessment (MSICDA) strategy, which involves an initial virtual screening of over 1.5 million SPs, followed by comprehensive simulations amounting to 154.54 µs across 5418 of instances. The MSICDA method provides a detailed and holistic stability view of peptide-protein interactions, systematically isolated optimized peptides and identified two leading candidates, DA#430 and DA#99409, characterized by their enhanced stability, optimized binding, and high affinity toward the CREBBP-BrD. In cell-free assays, DA#430 and DA#99409 exhibited 2- to 12-fold greater potency than inhibitor SGC-CBP30. Cell studies revealed higher peptide selectivity for cancerous versus normal cells over small molecules. DA#430 combined with (+)-JQ-1 showed promising synergistic effects. Our approach enables the identification of peptides with optimized binding, high affinity, and enhanced stability, leading to more precise and effective cyclic peptide design, thereby establishing MSICDA as a generalizable and transformative tool for uncovering novel targeted drug development in various therapeutic areas.

Identification of CRKL as an oncogenic biomarker for prognosis and immunotherapy in melanoma, and its potential molecular mechanism.

CRKL (CRK Like Proto-Oncogene) belongs to the Crk family and is a 39-kDa adapter protein that encodes SH2 and SH3 (src homologs) domains. To identify its oncogenic role in malignant melanoma, we investigated the association between CRKL and mutation, prognosis, tumor mutation burden, immune cell infiltration of melanoma, and explored the associations between CRKL and immunotherapy response. Our results showed that abnormal CRKL expression is associated with poor prognosis in melanoma and is significantly correlated with immune-activated pathways and processes, immune cell infiltrations, and expression of immunoregulators. Importantly, we found that CRKL expression is a predictive biomarker for anti-PD1 therapy response in melanoma patients. Furthermore, inhibiting CRKL expression in melanoma cell lines suppressed their proliferation and metastasis, as well as activated the pyroptosis-related pathway. Our study provides potential mechanisms of melanoma pathogenesis, which may suggest new avenues for targeted therapy in this disease.

Conservation Strategies for Aquilaria sinensis: Insights from DNA Barcoding and ISSR Markers.

The evergreen tree species Aquilaria sinensis holds significant economic importance due to its specific medicinal values and increasing market demand. However, the unrestricted illegal exploitation of its wild population poses a threat to its survival. This study aims to contribute to the conservation efforts of A. sinensis by constructing a library database of DNA barcodes, including two chloroplast genes (psbA-trnH and matK) and two nuclear genes (ITS and ITS2). Additionally, the genetic diversity and structure were estimated using inter-simple sequence repeats (ISSR) markers. Four barcodes of 57 collections gained 194 sequences, and 1371 polymorphic bands (98.63%) were observed using DNA ISSR fingerprinting. The Nei's gene diversity (H) of A. sinensis at the species level is 0.2132, while the Shannon information index (I) is 0.3128. The analysis of molecular variance revealed a large significant proportion of total genetic variations and differentiation among populations (Gst = 0.4219), despite a relatively gene flow (Nm = 0.6853) among populations, which were divided into two groups by cluster analysis. There was a close genetic relationship among populations with distances of 0.0845 to 0.5555. This study provides evidence of the efficacy and dependability of establishing a DNA barcode database and using ISSR markers to assess the extent of genetic diversity A. sinensis. Preserving the genetic resources through the conservation of existing populations offers a valuable proposition. The effective utilization of these resources will be further deliberated in subsequent breeding endeavors, with the potential to breed agarwood commercial lines.

Distinct functions of dimeric and monomeric scaffold protein Alix in regulating F-actin assembly and loading of exosomal cargo.

Alix is a ubiquitously expressed scaffold protein that participates in numerous cellular processes related to the remodeling/repair of membranes and the actin cytoskeleton. Alix exists in monomeric and dimeric/multimeric configurations, but how dimer formation occurs and what role the dimer has in Alix-mediated processes are still largely elusive. Here, we reveal a mechanism for Alix homodimerization mediated by disulfide bonds under physiological conditions and demonstrate that the Alix dimer is enriched in exosomes and F-actin cytoskeleton subcellular fractions. Proteomic analysis of exosomes derived from Alix-/- primary cells underlined the indispensable role of Alix in loading syntenin into exosomes, thereby regulating the cellular levels of this protein. Using a set of deletion mutants, we define the function of Alix Bro1 domain, which is solely required for its exosomal localization, and that of the V domain, which is needed for recruiting syntenin into exosomes. We reveal an essential role for Cys814 within the disordered proline-rich domain for Alix dimerization. By mutating this residue, we show that Alix remains exclusively monomeric and, in this configuration, is effective in loading syntenin into exosomes. In contrast, loss of dimerization affects the ability of Alix to associate with F-actin, thereby compromising Alix-mediated cytoskeleton remodeling. We propose that dimeric and monomeric forms of Alix selectively execute two of the protein's main functions: exosomal cargo loading and cytoskeleton remodeling.

Analysis of the chloroplast genome and phylogenetic evolution of Bidens pilosa.

Chloroplast genomes for 3 Bidens plants endemic to China (Bidens bipinnata Linn., Bidens pilosa Linn., and Bidens alba var. radiata) have been sequenced, assembled and annotated in this study to distinguish their molecular characterization and phylogenetic relationships. The chloroplast genomes are in typical quadripartite structure with two inverted repeat regions separating a large single copy region and a small single copy region, and ranged from 151,599 to 154,478 bp in length. Similar number of SSRs and long repeats were found in Bidens, wherein mononucleotide repeats (A/T), forward and palindromic repeats were the most in abundance. Gene loss of clpP and psbD, IR expansion and contraction were detected in these Bidens plants. It seems that ndhE, ndhF, ndhG, and rpl32 from the Bidens plants were under positive selection while the majority of chloroplast genes were under purifying selection. Phylogenetic analysis revealed that 3 Bidens plants clustered together and further formed molophyletic clade with other Bidens species, indicating Bidens plants might be under radiation adaptive selection to the changing environment world-widely. Moreover, mutation hotspot analysis and in silico PCR analysis indicated that inter-genic regions of ndhD-ccsA, ndhI-ndhG, ndhF-rpl32, trnL_UAG-rpl32, ndhE-psaC, matK-rps16, rps2-atpI, cemA-petA, petN-psbM were candidate markers of molecular identification for Bidens plants. This study may provide useful information for genetic diversity analysis and molecular identification for Bidens species.

Genome-wide characterization of regulator of chromosome condensation 1 (RCC1) gene family in Artemisia annua L. revealed a conservation evolutionary pattern.

BACKGROUND: Artemisia annua is the major source for artemisinin production. The artemisinin content in A. annua is affected by different types of light especially the UV light. UVR8, a member of RCC1 gene family was found to be the UV-B receptor in plants. The gene structures, evolutionary history and expression profile of UVR8 or RCC1 genes remain undiscovered in A. annua. RESULTS: Twenty-two RCC1 genes (AaRCC1) were identified in each haplotype genome of two diploid strains of A. annua, LQ-9 and HAN1. Varied gene structures and sequences among paralogs were observed. The divergence of most RCC1 genes occurred at 46.7 - 51 MYA which overlapped with species divergence of core Asteraceae during the Eocene, while no recent novel RCC1 members were found in A. annua genome. The number of RCC1 genes remained stable among eudicots and RCC1 genes underwent purifying selection. The expression profile of AaRCC1 is analogous to that of Arabidopsis thaliana (AtRCC1) when responding to environmental stress. CONCLUSIONS: This study provided a comprehensive characterization of the AaRCC1 gene family and suggested that RCC1 genes were conserved in gene number, structures, constitution of amino acids and expression profiles among eudicots.

Extra-High Mechanical and Phononic Anisotropy in Black Phosphorus Blisters.

Strain is an effective strategy to modulate the electrical, optical, and optoelectronic properties of 2D materials. Conventional circular blisters could generate a biaxial stretching of 2D membranes with notable strain gradients along the hoop direction. However, such a deformation mode cannot be utilized to investigate mechanical responses of in-plane anisotropic 2D materials, for example, black phosphorus (BP), due to its crystallographic orientation dependence. Here, a novel rectangular-shaped bulge device is developed to uniaxially stretch the membrane, and further provide a promising platform to detect orientation-dependent mechanical and optical properties of anisotropic 2D materials. Impressively, the derived anisotropic ratio of Young's modulus of BP flakes is much higher than the values obtained via the nanoindentation method. The extra-high strain-dependent phononic anisotropy in Raman modes along different crystalline orientations is also observed. The designed rectangular budge device expands the uniaxial deformation methods available, allowing to explore the mechanical, and strain-dependent physical properties of other anisotropic 2D materials more broadly.

The chain mediating roles of anxiety and depression in the relationship between the effects of the COVID-19 pandemic and procrastination in adolescents: a longitudinal study.

BACKGROUND: The relationship between the Coronavirus Disease 2019 (COVID-19) pandemic, which is a traumatic event for adolescents, and procrastination is not clear. Mental health may play an important role in this relationship; however, the underlying mechanisms remain unknown. This study aimed to construct chain mediation models to examine whether anxiety and depression symptoms mediate the effects of the COVID-19 pandemic on procrastination in adolescents. METHODS: A convenience sample of 12 middle and high schools in Harbin, China, with four follow-up online surveys was conducted during the COVID-19 pandemic. A total of 4,156 Chinese adolescents were enrolled in this study, of whom ages 11-18 (Mean = 13.55; SD = 1.18), 50.75% were male, and 93.24% were middle school students. Descriptive demographic analysis and Pearson's correlation analysis of the effects of the COVID-19 pandemic (T1), anxiety(T2), depression (T3), and procrastination (T4) were performed in SPSS 22.0. Chain mediation analysis performed with Mplus 8.3. RESULTS: The effects of the COVID-19 pandemic, anxiety symptoms, depression symptoms, and procrastination were positively correlated (P < 0.01). The effects of the COVID-19 pandemic have a direct link on adolescent procrastination (effect = 0.156; SE = 0.031; 95%CI: 0.092, 0.214), and have three indirect paths on procrastination: the independent mediating role of anxiety symptoms was 29.01% (effect = 0.047; SE = 0.012; 95%CI: 0.024, 0.072), the independent mediating role of depression symptoms was 29.01% (effect = 0.047; SE = 0.010; 95%CI: 0.030, 0.068), as well as the completely chain mediating role of anxiety and depression symptoms was 15.43% (effect = 0.025; SE = 0.005; 95%CI: 0.017, 0.036). CONCLUSIONS: Our results suggest that anxiety and depressive symptoms are part of a causal chain between the effects of the COVID-19 pandemic and procrastination among Chinese adolescents. To effectively reduce their procrastination, attention should be paid to the emotional distress caused to adolescents by major events such as the COVID-19 epidemic. All data were taken from self-reported measures and one city in China, which may bias the results and limit their generalizability.

Efficient Hot Electron Capture in CuPc/MoSe2 Heterostructure Assisted by Intersystem Crossing.

Efficient hot electron extraction is a promising approach to develop photovoltaic devices that exceed the Shockley-Queisser limit. However, experimental evidence of hot electron harvesting employing an organic-inorganic interface is still elusive. Here, we reveal the hot electron dynamics at a CuPc/MoSe2 interface using steady-state spectroscopy and transient absorption spectroscopy. A hot electron transfer efficiency of greater than 78% from MoSe2 to CuPc is observed, comparable to that achieved in quantum dot hybrid systems. The mechanism is proposed as follows: the photogenerated hot electrons in MoSe2 transfer to CuPc and form singlet charge transfer states, which subsequently transform into triplet charge transfer states assisted by the rapid intersystem crossing, inhibiting back-donation of electrons and facilitating exciton dissociation into CuPc polarons with a nanosecond lifetime. Our results demonstrate that the intersystem crossing of the hybrid electronic state at organic-inorganic interfaces may serve as a scheme to enable efficient hot electron extraction in photovoltaic devices.

Local Chiral Inversion of Thymine Dimers by Manipulating Single Water Molecules.

Water, as one of the most important and indispensable small molecules in vivo, plays a crucial role in driving biological self-assembly processes. Real-space detection and identification of water-induced organic structures and further capture of dynamic dehydration processes are important yet challenging, which would help to reveal the cooperation and competition mechanisms among water-involved noncovalent interactions. Herein, introduction of water molecules onto the self-assembled thymine (T) structures under ultrahigh vacuum (UHV) conditions results in the hydration of hydrogen-bonded T dimers forming a well-ordered water-involved T structure. Reversibly, a local dehydration process is achieved by in situ scanning tunneling microscopy (STM) manipulation on single water molecules, where the adjacent T dimers connected with water molecules undergo a local chiral inversion process with the hydrogen-bonding configuration preserved. Such a strategy enables real-space identification and detection of the interactions between water and organic molecules, which may also shed light on the understanding of biologically relevant self-assembly processes driven by water.

Comparative chloroplast genome analyses of Amomum: insights into evolutionary history and species identification.

BACKGROUND: Species in genus Amomum always have important medicinal and economic values. Classification of Amomum using morphological characters has long been a challenge because they exhibit high similarity. The main goals of this study were to mine genetic markers from cp genomes for Amomum species identification and discover their evolutionary history through comparative analysis. RESULTS: Three species Amomum villosum, Amomum maximum and Amomum longipetiolatum were sequenced and annotated for the complete chloroplast (cp) genomes, and the cp genomes of A. longipetiolatum and A. maximum were the first reported. Three cp genomes exhibited typical quadripartite structures with 163,269-163,591 bp in length. Each genome encodes 130 functional genes including 79 protein-coding, 26 tRNAs and 3 rRNAs genes. 113-152 SSRs and 99 long repeats were identified in the three cp genomes. By designing specific primers, we amplified the highly variable loci and the mined genetic marker ccsA exhibited a relatively high species identification resolution in Amomum. The nonsynonymous and synonymous substitution ratios (Ka/Ks) in Amomum and Alpinia showed that most genes were subjected to a purifying selection. Phylogenetic analysis revealed the evolutionary relationships of Amomum and Alpinia species and proved that Amomum is paraphyletic. In addition, the sequenced sample of A. villosum was found to be a hybrid, becoming the first report of natural hybridization of this genus. Meanwhile, the high-throughput sequencing-based ITS2 analysis was proved to be an efficient tool for interspecific hybrid identification and with the help of the chloroplast genome, the hybrid parents can be also be determined. CONCLUSION: The comparative analysis and mined genetic markers of cp genomes were conducive to species identification and evolutionary relationships of Amomum.

Performances of clinical characteristics and radiological findings in identifying COVID-19 from suspected cases.

BACKGROUND: To identify effective factors and establish a model to distinguish COVID-19 patients from suspected cases. METHODS: The clinical characteristics, laboratory results and initial chest CT findings of suspected COVID-19 patients in 3 institutions were retrospectively reviewed. Univariate and multivariate logistic regression were performed to identify significant features. A nomogram was constructed, with calibration validated internally and externally. RESULTS: 239 patients from 2 institutions were enrolled in the primary cohort including 157 COVID-19 and 82 non-COVID-19 patients. 11 features were selected by LASSO selection, and 8 features were found significant using multivariate logistic regression analysis. We found that the COVID-19 group are more likely to have fever (OR 4.22), contact history (OR 284.73), lower WBC count (OR 0.63), left lower lobe involvement (OR 9.42), multifocal lesions (OR 8.98), pleural thickening (OR 5.59), peripheral distribution (OR 0.09), and less mediastinal lymphadenopathy (OR 0.037). The nomogram developed accordingly for clinical practice showed satisfactory internal and external validation. CONCLUSIONS: In conclusion, fever, contact history, decreased WBC count, left lower lobe involvement, pleural thickening, multifocal lesions, peripheral distribution, and absence of mediastinal lymphadenopathy are able to distinguish COVID-19 patients from other suspected patients. The corresponding nomogram is a useful tool in clinical practice.

Assessment of an Artificial Intelligence Mandibular Osteotomy Design System: A Retrospective Study.

BACKGROUND: In this study, an AI osteotomy software was developed to design the presurgical plan of mandibular angle osteotomy, which is followed by the comparison between the software-designed presurgical plan and the traditional manual presurgical plan, thus assessing the practicability of applying the AI osteotomy software in clinical practices. METHODS: (1) Develop an AI osteotomy software: design an algorithm based on convolutional neural networks capable of learning feature point and processing clustering segmentation; then, select 2296 cases of successful 3D mandibular angle osteotomy presurgical plans, followed by using those 2296 cases to train the deep learning algorithm; (2) compare the osteotomy presurgical plan of AI osteotomy software and that of manual: first step: randomly selecting 80 cases of typical female head 3D CTs, and designing those 80 cases by means of AI osteotomy software designing (group A) and manually designing (group B), respectively; second step: comparing several indexes of group A and those of group B, including the efficiency index (time from input original CT data to osteotomy presurgical plan output), the safety index (the minimum distance from the osteotomy plane to the mandibular canal), the symmetry indexes (bilateral difference of mandibular angle, mandibular ramus height and mandibular valgus angle) and aesthetic indexes (width ratio between middle and lower faces (M/L), mandibular angle and mandibular valgus angle). RESULTS: The efficiency index: the design time of group A is 1.768 ± 0.768 min and that of group B is 26.108 ± 1.137 min, with P = 0.000; the safety index: The minimum distances from the osteotomy plane to the mandibular canal are 3.908 ± 0.361mm and 3.651 ± 0.437mm, p = 0.117 in groups A and B, respectively; The symmetry indexes: Bilateral differences of mandibular angle are 1.824 ± 1.834° and 1.567 ± 1.059° in groups A and B, respectively, with P = 0.278; bilateral differences of mandibular ramus height are 2.083 ± 1.263 and 2.965 ± 1.433, respectively, with P = 0.119 in groups A and B; Aesthetic indexes: M/L in groups A and B is 1.364 ± 0.074 and 1.371 ± 0.067, respectively, with P = 0.793; mandibular angles in groups A and B are 127.724 ± 5.800° and 127.242 ± 5.545°, respectively, with P = 0.681; Valgus angles in groups A and B are 11.474 ± 5.380 and 9.743 ± 4.620, respectively, with P = 0.273. CONCLUSIONS: With high efficiency, as well as safety, symmetry and aesthetics equivalent to those of a manual design, the AI osteotomy software designing can be used as an alternative method for manual osteotomy designing. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

On-Surface Synthesis of [3]Radialenes via [1+1+1] Cycloaddition.

[3]Radialenes are the smallest carbocyclic structures with unusual topologies and cross-conjugated π-electronic structures. Here, we report a novel [1+1+1] cycloaddition reaction for the synthesis of aza[3]radialenes on the Ag(111) surface, where the steric hindrance of the chlorine substituents guides the selective and orientational assembling of the isocyanide precursors. By combining scanning tunneling microscopy, non-contact atomic force microscopy, and time-of-flight secondary ion mass spectrometry, we determined the atomic structure of the produced aza[3]radialenes. Furthermore, two reaction pathways including synergistic and stepwise are proposed based on density functional theory calculations, which reveal the role of the chlorine substituents in the activation of the isocyano groups via electrostatic interaction.

Ladder Phenylenes Synthesized on Au(111) Surface via Selective [2+2] Cycloaddition.

Ladder phenylenes (LPs) composed of alternating fused benzene and cyclobutadiene rings have been synthesized in solution with a maximum length no longer than five units. Longer polymeric LPs have not been obtained so far because of their poor stability and insolubility. Here, we report the synthesis of linear LP chains on the Au(111) surface via dehalogenative [2+2] cycloaddition, in which the steric hindrance of the methyl groups in the 1,2,4,5-tetrabromo-3,6-dimethylbenzene precursor improves the chemoselectivity as well as the orientation orderliness. By combining scanning tunneling microscopy and noncontact atomic force microscopy, we determined the atomic structure and the electronic properties of the LP chains on the metallic substrate and NaCl/Au(111). The tunneling spectroscopy measurements revealed the charged state of chains on the NaCl layer, and this finding is supported by density functional theory calculations, which predict an indirect bandgap and antiferromagnetism in the polymeric LP chains.

Lower expression of Hsa_circRNA_102682 in diabetic hyperhomocysteinemia negatively related to creatinemia is associated with TGF-ß and CTGF.

BACKGROUND: Diabetic nephropathy is a kidney disease caused by long-term hyperglycemia. Hsa_circRNA_102682 is related to the pathogenesis of preeclampsia. Preeclampsia is related to hypertension and proteinuria, and diabetic nephropathy is mainly manifested by hypertension and proteinuria. The main pathological change in diabetic nephropathy is glomerular fibrosis. METHODS: This study used serum samples of patients treated at Li Huili Eastern Hospital, Ningbo, China, from July 10, 2018 to February 15, 2019. We included 73 patients with diabetes and divided them into a normal-homocysteine group and a high-homocysteine group. We selected used quantitative reverse transcriptase-polymerase chain reaction to measure Hsa_circRNA_102682 concentration in the serum. Serum transforming growth factor-beta and connective tissue growth factor levels were tested using ELISA. The Pearson correlation test was used to assess the correlations between Hsa_circRNA_102682, transforming growth factor-beta, connective tissue growth factor, homocysteine, and creatinine. RESULT: Hsa_circRNA_102682 was significantly lower in diabetic patients with high levels of homocysteine than in those with normal levels of homocysteine, whereas transforming growth factor-beta and connective tissue growth factor levels were higher in diabetic patients with hyperhomocysteinemia. Hsa_circRNA_102682 was negatively correlated with the levels of transforming growth factor-beta, connective tissue growth factor, homocysteine, and creatinine. Transforming growth factor-beta and connective tissue growth factor were both positively correlated with homocysteine and creatinine. CONCLUSION: Low Hsa_circRNA_102682 was associated with high levels of transforming growth factor-beta and connective tissue growth factor as well as homocysteine and creatinine. These results suggest that Hsa_circRNA_102682 might be related to the pathogenesis of hyperhomocysteinemia in diabetic nephropathy.

Negative emotions, self-care activities on glycemic control in adults with type 2 diabetes: a cross-sectional study.

Glycemic control has become a focus of concern among diabetic patients. However, only 26.71% of patients achieved better glycemic control in China. Given the complexity of glycemic control, it is worth investigating the potential mechanisms between negative emotions and glycemic control. A total of 428 participants were recruited from a tertiary hospital (the number of hospital beds>500). They completed questionnaires consisting of demographics, Zung Self-Assessed Anxiety Scale(SAS), Zung Self-Assessed Depression Scale(SDS), and the Summary of Diabetes Self-Care Activities (SDSCA). HbA1 c was used to measure glycemic control. Descriptive analysis, Pearson correlation analysis, and Bootstrap analysis were conducted to analyze data. A total of 428 questionnaires were distributed, with 28 invalid questionnaires (93.46% were valid). Depression and self-care activities (exercise, medication) were associated with glycemic control. At the same time, the Bootstrap analysis revealed that self-care activities (exercise: standardized coefficient ß = 0.0181, p < 0.05, medication: standardized coefficient ß = 0.0211, p < 0.05) mediated the relationship between depression and glycemic control.

Bond-Scission-Induced Structural Transformation from Cumulene to Diyne Moiety and Formation of Semiconducting Organometallic Polyyne.

The structural transformation from symmetric cumulene to broken-symmetry polyyne within a one-dimensional (1-D) atomic carbon chain is a signature of Peierls distortion. Direct observation of such a structural transformation with single-bond resolution is, however, still challenging. Herein, we design a molecule with a cumulene moiety (Br2C═C═C═CBr2) and employ STM tip manipulation to achieve the molecular skeleton rearrangement from a cumulene to a diyne moiety (Br-C≡C-C≡C-Br). Furthermore, by an on-surface reaction strategy, thermally induced entire debromination (:C═C═C═C:) leads to the formation of a 1-D organometallic polyyne (-C≡C-C≡C-Au-) with a semiconducting characteristic, which implies that a Peierls-like transition may occur in a rationally designed molecular system with limited length.

Lateral force calibration for atomic force microscope cantilevers using a suspended nanowire.

Friction measurement via atomic force microscope (AFM) relies on accurate calibration for the torsional spring constant of the AFM cantilever and its lateral deflection sensitivity. Here we describe a method that employs a suspended nanowire (SNW) as a reference beam to quantify the torsional spring constant of AFM cantilevers. Based on the fact that a uniform SNW with cylindrical symmetry has an identical spring constant when bent in any direction perpendicular to its axis, the spring constant of the SNW in a normal direction is determined by an AFM cantilever with a known normal spring constant, and is subsequently used as a force transfer standard to calibrate the torsional spring constant of the AFM cantilever. The lateral deflection sensitivity can be accurately measured by pushing the AFM tip laterally on the groove edge. The calibration result is compared to the well-known diamagnetic lateral force calibrator method and shows an uncertainty of 15% or better. The presented method is applicable for the lateral force calibration of AFM cantilevers in a wide range of instruments including inverted configurations and in an ultrahigh vacuum.

Bifacial Raman Enhancement on Monolayer Two-Dimensional Materials.

Understanding the charge interaction between molecules and two-dimensional (2D) materials is essential for the design of functional devices. Here, we report the bifacial Raman enhancement of molecules on monolayer graphene and hexagonal boron nitride ( h-BN). Taking advantage of the atomically thick layered structure, we show that both surfaces of 2D materials can interact with molecules and simultaneously enhance their Raman scattering. Different enhancement features were observed for monolayer graphene and h-BN. The intensity decrease of particular Raman modes of copper phthalocyanine (CuPc) on both surfaces of h-BN suggests that z-dipoles exist and are partially canceled out between the two interfaces, while the twice Raman intensities of the characteristic Raman modes of CuPc on both surfaces of graphene compared to that on one surface evidenced the charge transfer process. These results provide an approach to modify 2D materials by bifacial adsorption of molecules, and the findings can inspire the design of functional 2D material-based devices.