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Chiral molecule assignation is crucial for asymmetric catalysis, functional materials, and the drug industry. The conventional approach requires theoretical calculations of electronic circular dichroism (ECD) spectra, which is time-consuming and costly. To speed up this process, we have incorporated deep learning techniques for the ECD prediction. We first set up a large-scale dataset of Chiral Molecular ECD spectra (CMCDS) with calculated ECD spectra. We further develop the ECDFormer model, a Transformer-based model to learn the chiral molecular representations and predict corresponding ECD spectra with improved efficiency and accuracy. Unlike other models for spectrum prediction, our ECDFormer creatively focused on peak properties rather than the whole spectrum sequence for prediction, inspired by the scenario of chiral molecule assignation. Specifically, ECDFormer predicts the peak properties, including number, position, and symbol, then renders the ECD spectra from these peak properties, which significantly outperforms other models in ECD prediction, Our ECDFormer reduces the time of acquiring ECD spectra from 1-100 hours per molecule to 1.5s., Comment: 14 pages, 8 Figures, Submitted to Nature Machine Intelligence

Kaiyuan Zhang,1,* Ziyue Luo,1,* Xinchao Zhu,1 Xinyi Yao,1 Dingqi Lu,2 Liying Chen,1 Tao Hong,1 Yating Ren,1 Xinchang Wang3 1Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China; 2First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China; 3Department of Rheumatology, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinchang Wang, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, People’s Republic of China, Tel +86 13065714635, Email ossani@126.comPurpose: Sjogren’s Syndrome (SS) is a systemic autoimmune disease primarily characterized by dysfunction of the exocrine glands. Research into the etiology and pathogenesis of salivary glands (SG) inflammation of SS is very limited. The aim of this study was to identify potential pyroptosis-related genes in SG inflammation through bioinformatics analysis and validation of the SG in SS.Methods: GSE157159 dataset and GSE159574 dataset were downloaded from Gene Expression Omnibus (GEO). Differentially Expressed Genes (DEGs) analysis was used to screen DEGs from SS and non-SS SG samples. Pyroptosis-related genes were obtained from GeneCards. After intersecting DEGs with pyroptosis-related genes, the pyroptosis-related DEGs in SS were obtained. Subsequently, ClueGO enrichment analysis, Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis, Protein-protein Interaction (PPI), and identification and co-expression analysis of hub genes were performed. Subsequently, we collected SG samples from 17 SS patients and 17 non-SS patients and validated the expression of two hub genes (GZMA, GBP1) and characteristic genes (GSDMD) of pyroptosis through

Donghai Zhou,1,* Xue Yu,2,* Kai Yu,3 Yating Ren,2 Kepeng Yang,1 Xinchang Wang,1 Qiao Wang4 1Department of Rheumatology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310005, People’s Republic of China; 2The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310005, People’s Republic of China; 3Department of Hepatology 1, Xixi Hospital of Hangzhou, Hangzhou, Zhejiang Province, 310023, People’s Republic of China; 4College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiao Wang; Xinchang Wang, Email wangqiao0309@163.com; ossani@126.comBackground: Primary Sjögren’s syndrome (pSS) is an autoimmune disease with lymphocytic infiltration of the salivary and lachrymal glands, whose present disease-specific objective indicators are few and have shortcomings that should be addressed. An integrated analysis of sequencing data from different cohorts has the potential to unveil novel biomarkers in pSS.Methods: We identified 3 GEO datasets, including gene expression data from minor salivary gland (MSG) biopsy samples of 49 patients with pSS and 31 non-pSS and whole blood cells of 30 pSS patients and 30 healthy controls (HCs). Differentially expressed genes (DEGs) involved in pSS were identified from these datasets. Function Enrichment Analyses of common upregulated DEGs and PPI (protein-protein interaction) networks were performed. Furthermore, we have carried out further analysis of these DEGs to explore their potential clinical significance and diagnostic efficacy as a biomarker for pSS. Sterile Alpha Motif Domain Containing 9 Like (SAMD9L), one of the DEGs, has been identified as a promising candidate biomarker that correlates with the severity of pSS. This has been validated by analyzing local clinical

Dingqi Lu,1,* Xinchao Zhu,2,* Tao Hong,2 Xinyi Yao,2 Zhiming Xie,3 Liying Chen,2 Yihan Wang,2 Kaiyuan Zhang,2 Yating Ren,2 Yi Cao,4 Xinchang Wang3 1First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China; 2Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China; 3The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China; 4The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinchang Wang, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, People’s Republic of China, Tel +86 13065714635, Email ossani@126.comPurpose: Systemic lupus erythematosus is a heterogeneous autoimmune disease in which skin involvement is a common manifestation. It is currently thought that the photosensitivity of SLE skin involvement is associated with anti-SSA antibodies. This study aimed to expand the current state of knowledge surrounding the molecular pathophysiology of SLE skin photosensitivity through Serum metabolomics analysis.Patients and Methods: The serum metabolites of 23 cases of skin-involved SLE (SI) group, 14 cases of no SI (NSI) group, and 30 cases of healthy controls (HC) were analyzed by using UPLC-MS/MS technology, and subgroup analysis was performed according to the expression of anti-SSA antibodies in SI. MetaboAnalyst 5.0 was used for enrichment analysis and ROC curve construction, identifying serum metabolic markers of skin-involved SLE associated with anti-SSA antibodies.Results: We identified several metabolites and metabolic pathways associated with SLE photosensitivity. Two metabolites, SM (d18:1/24:0) and gamma-CEHC can di

Nitrogen doped diamonds with great application potentials can be synthesized by using different doping sources (i.e., urea and N2), effects of which on growth behavior and properties of diamond films on WC-Co substrates were presented in this paper. The doping efficiency of urea was always higher than 0.12, much higher than that of N2 (always lower than 0.04). The sufficient N2 addition could increase growth rate, and induce apparent grain nanocrystallization, by modifying reactant gas phase chemistry. The grain nanocrystallization contributed more to the reduction of the surface roughness, and degradation of the diamond purity and mechanical properties. On the contrary, the urea doping resulted in much less degradation of the diamond purity and mechanical properties, while providing sufficient N incorporations into the diamonds. Besides, urea doping promoted the formation of the diamond (220) planes on the polycrystalline diamond surfaces, which had a close relationship with the actual N doping concentration in the diamond. The controllable adjustment of the growth and properties of diamond films, by selecting the doping source and optimizing the doping ratio, could help to meet distinctive application requirements, and balance the machining efficiency and application performance of diamond coated components.

Yihan Wang,1,* Yating Ren,1,* Tao Hong,1 Dingqi Lu,2 Fan Zhang,2 Yi Cao,3 Xinchang Wang4 1Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Department of Dermatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 4Department of Rheumatology, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinchang Wang, Department of Rheumatology, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, People’s Republic of China, Tel +86 0571-85288249, Email ossani@126.comPurpose: Neuropsychiatric lupus (NPSLE) is one of the important manifestations of systemic lupus erythematosus. Previous studies mainly focused on the disruption of the blood-brain barrier and the production of brain-reactive autoantibodies, However, there is no comprehensive lipidomic analysis in NPSLE. Therefore, this research evaluated the lipidomic analysis in the hippocampus and liver of NPSLE mice with mood disorders, to explore the influence of the liver-brain axis on this disease.Methods: MRL/lpr mice and MRL/mpj mice were respectively used as NPSLE and control groups. Behavioral tests and systemic disease characteristics of mice were assessed at the age of 18 weeks. Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) was used for lipid metabolite determination. Multivariate statistical analysis was used to identify lipid metabolites that were differentially expressed in two groups.Results: Our results showed that 355 and 405 lipid metabolites were differentially expressed between the NPSLE and control groups in the hippocampus and liver. According to the pathway e

H-, O-, OH- and F-terminated N-doped diamond surfaces are calculated by the density functional theory in the present study. Combined effects of terminating species and substitutional N dopants in the 1st or 2nd carbon layers on several critical features (i.e., bond length, total electron density, bond population, atomic charge, Fukui function, and density-of-states) are systematically studied and discussed. The N dopant presents clear, but local, effects for all the terminating species and dopant positions. The adsorption of any individual species to the N dopant in the 1st carbon layer results in the reduction of adsorption energy (less negative), most probably owing to the full shell structure of this N dopant. The H, OH and F each provides one unpaired electron to occupy the antibonding states within the N-H, N-OH and N-F bonds, making the bonds elongated, reducing the corresponding electron densities and bond populations. On the contrary, the N dopant in the 2nd carbon layer induces slight increment of the adsorption energy for O, OH and F, attributed to the positive atomic charges of neighboring topmost C atoms. Amongst the four adsorbates, the O shows the highest reactivity to either an electrophilic or a nucleophilic attack. Besides, N dopants have slight influences on the reactivity of the adjacent adsorbates. The present results can help to understand some related chemical processes (such as the oxidation and electrochemical analysis) on N-doped diamond films.

Liying Chen,1,* Dingqi Lu,2,* Kai Yu,1 Shiya He,1 Liu Liu,1 Xvfeng Zhang,1 Bo Feng,3 Xinchang Wang4 1Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China; 2First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China; 3Department of Nephrology, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, Zhejiang Province, 314001, People’s Republic of China; 4Department of Rheumatology, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinchang WangDepartment of Rheumatology, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, People’s Republic of ChinaTel +86 13065714635Email ossani@126.comPurpose: Sjögren’s syndrome (SS) is a systemic autoimmune disease mainly characterized by dysfunction of exocrine glands. Studies on diagnosis models specific for SS patients are very limited. We aimed to use gene expression datasets from salivary glands to identify aberrant differentially expressed genes (DEGs) and pathways by bioinformatics and validate candidate genes by clinical minor labial gland biopsy (MSGB) samples, and finally build a combined gene quantitative diagnosis model of SS.Patients and Methods: Original datasets GSE23117, GSE7451, and GSE127952 were obtained from the Gene Expression Omnibus database (GEO) and integrated and analyzed for differentially expressed genes in SS salivary glands. ClueGO and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of upregulated and downregulated DEGs were performed, and protein–protein interaction (PPI) networks were constructed using the STRING and Cytoscape database. H&E staining and immunohistochemistry were used to val

A method based on the density functional theory calculations is proposed for predicting the influences of dopants on the diamond oxidation, by evaluating the O adsorption energy, chemical bond weakening related to desorption, and probable products. It is proven by verification tests that oxidation resistances of the diamond materials can be indeed selectively controlled (e.g., -36 to 54.3% for diamond films, -36.5 to 45.1% for diamond grits) by adding various doping sources ((CH3O)(3)B, Si(OC2H5)(4), N-2, and CO(NH2)(2)), attributed to their direct impurity incorporation, or modified gas chemistry. B and Si dopings can improve the oxidation resistance, but the addition of N-2 or urea plays an opposite role. Reactive ion etching and chemomechanical polishing tests are also accomplished, further demonstrating the influences of dopings on oxidation-related processes. This study paves the way for enhancing the efficiencies of the ultraprecision machining and micro-nano machining on the diamonds. Most importantly, the proposed prediction method can be potentially used in similar cases with other dopants and in other materials.

Isolation of circulating tumor cells (CTCs) from blood samples has important prognostic and therapeutic implications for cancer treatments, but the process is very challenging due to the low concentration of CTCs. In this study, we report a novel 3D printed microfluidic device functionalized with anti-EpCAM (epithelial cell adhesion molecule) antibodies to isolate CTCs from human blood samples. A 3D printing technology was utilized with specially designed interior structures to fabricate a microfluidic device with high surface area and fluid flow manipulation, increasing capture efficiency of tumor cells. These devices with the optimal flow rate (1 mL/h) and channel length (2 cm) were demonstrated to test three kinds of EpCAM positive cancer cell lines (MCF-7 breast cancer, SW480 colon cancer, and PC3 prostate cancer), and one kind of EpCAM negative cancer cell line (293T kidney cancer). Experimentally, the capture efficiency higher than 90% has been achieved, and the isolation of MCF-7 tumor cells from spiked human blood samples has also been demonstrated. Combined with DNA-based detection (e.g. polymerase chain reaction or DNA sequencing), the detection and analysis of released DNAs from captured tumor cells could be another future direction for clinical diagnosis and cancer treatment.

The non- and O-terminated diamond (1 1 1)-1 x 1 surfaces, with the substitutional B (or N) dopants in different atomic layers, have been modelled in the present study. The influences of the O adsorbates, dopant and dopant position on the adsorption energy, have been studied by performing the density functional theory (DM) calculations. Various parameters were additionally calculated in order to analyze the obtained results: bond lengths, total electron densities, bond populations, atomic charges, Fukui functions (FFs) and density-of-states. Dangling bonds on non-terminated surfaces, O adsorbates, as well as dopants within various atomic layers were all found to induce local effects. In fact, the degree of influences of the dopant on the adsorption energy of the O adsorbates, as well as on parameters like the near-surface bond lengths, total electron density, bond populations and atomic charges, were all found to be dependent on the dopant position. More generally, the deeper the dopant position, the less influence it had on the surface structures and properties. The influences by the dopant in the 1st or 2nd C atomic layer were observed to be significant, but those in the 3rd to 5th C layers were almost negligible. It was also found that the B dopant would decrease the adsorption energy of the adjacent O adsorbates, while the N dopant in the 2nd layer would increase it. Furthermore, the combination of the O adsorbates, together with the dopants within the 1st or 2nd C layer, could induce significant elongation of the bonds between neighboring atoms within the 1st and 2nd layers (i.e. C-C, C-B or C-N bonds). Moreover, all the terminating O atoms could react strongly with either the electrophilic or the nucleophilic species.

Chiral amplification in molecular self-assembly has profound impact on the recognition and separation of chiroptical materials, biomolecules, and pharmaceuticals. An understanding of how to control this phenomenon is nonetheless restricted by the structural complexity in multicomponent self-assembling systems. Here, we create chiral octahedra incorporating a combination of chiral and achiral vertices and show that their discrete nature makes these octahedra an ideal platform for in-depth investigation of chiral transfer. Through the construction of dynamic combinatorial libraries, the unique possibility to separate and characterise each individual assembly type, density functional theory calculations, and a theoretical equilibrium model, we elucidate that a single chiral unit suffices to control all other units in an octahedron and how this local amplification combined with the distribution of distinct assembly types culminates in the observed overall chiral amplification in the system. Our combined experimental and theoretical strategy can be applied generally to quantify discrete multi-component self-assembling systems.

Chiral amplification in molecular self-assembly has profound impact on the recognition and separation of chiroptical materials, biomolecules, and pharmaceuticals. An understanding of how to control this phenomenon is nonetheless restricted by the structural complexity in multicomponent self-assembling systems. Here, we create chiral octahedra incorporating a combination of chiral and achiral vertices and show that their discrete nature makes these octahedra an ideal platform for in-depth investigation of chiral transfer. Through the construction of dynamic combinatorial libraries, the unique possibility to separate and characterise each individual assembly type, density functional theory calculations, and a theoretical equilibrium model, we elucidate that a single chiral unit suffices to control all other units in an octahedron and how this local amplification combined with the distribution of distinct assembly types culminates in the observed overall chiral amplification in the system. Our combined experimental and theoretical strategy can be applied generally to quantify discrete multi-component self-assembling systems.