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1.
Angew Chem Int Ed Engl ; 63(19): e202400644, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38470139

ABSTRACT

Chiral hybrid organic-inorganic metal halides (HOMHs) offer an ideal platform for the advancement of second-order nonlinear optical (NLO) materials owing to their inherent noncentrosymmetric structures. The enhancement of optical nonlinearity of chiral HOMHs could be achieved by matching the free exciton and/or self-trapped exciton energy levels with desired NLO frequencies. However, the current scarcity of resonance modes and low resonance ratio hamper the further improvements of NLO performance. Herein, we propose a new resonant channel of charge transfer (CT) excited states from metal halide polyhedra to organic ligand to boost the second-order optical nonlinearity of chiral HOMHs. The model lead halide (C7H10N)PbBr3 (C7H10N=1-ethylpyridinium) exhibits a drastically enhanced second harmonic generation in resonance to the deep CT exciton energy, with intensity of up to 111.0 times that of KDP and 10.9 times that of urea. The effective NLO coefficient has been determined to be as high as ~40.2 pm V-1, balanced with a large polarization ratio and high laser damage threshold. This work highlights the contribution of organic ligands in the construction of a resonant channel for enhancing second-order NLO coefficients of metal halides, and thus provides guidelines for designing new chiral HOMHs materials for advanced nonlinear photonic applications.

2.
Chem Sci ; 15(10): 3530-3538, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38455020

ABSTRACT

Stimuli-responsive optical materials have provided a powerful impetus for the development of intelligent optoelectronic devices. The family of organic-inorganic hybrid metal halides, distinguished by their structural diversity, presents a prospective platform for the advancement of stimuli-responsive optical materials. Here, we have employed a crown ether to anchor the A-site cation of a chiral antimony halide, enabling convenient control and modulation of its photophysical properties. The chirality-dependent asymmetric lattice distortion of inorganic skeletons assisted by a crown ether promotes the formation of self-trapped excitons (STEs), leading to a high photoluminescence quantum yield of over 85%, concomitant with the effective circularly polarized luminescence. The antimony halide enantiomers showcase highly sensitive stimuli-responsive luminescent behaviours towards excitation wavelength and temperature simultaneously, exhibiting a versatile reversible colour switching capability from blue to white and further to orange. In situ temperature-dependent luminescence spectra, time-resolved luminescence spectra and theoretical calculations reveal that the multi-stimuli-responsive luminescent behaviours stem from distinct STEs within zero-dimensional lattices. By virtue of the inherent flexibility and adaptability, these chiral antimony chlorides have promising prospects for future applications in cutting-edge fields such as multifunctional illumination technologies and intelligent sensing devices.

3.
PeerJ ; 12: e16854, 2024.
Article in English | MEDLINE | ID: mdl-38304193

ABSTRACT

Background: Acute pancreatitis is an unpredictable and potentially fatal condition for which no definitive cure is currently available. Our research focused on exploring the connection between body mass index, a frequently overlooked risk factor, and both the onset and progression of acute pancreatitis. Material/Methods: A total of 247 patients with acute pancreatitis admitted to Jiangsu Provincial Hospital of Chinese Medicine from January 2021 to February 2023 were retrospectively reviewed. After screening, 117 patients with complete height and body weight data were selected for detailed assessment. Additionally, 85 individuals who underwent physical examinations at our hospital during this period were compiled to create a control group. The study received ethical approval from the ethics committee of Jiangsu Province Hospital of Chinese Medicine (Ref: No.2022NL-114-02) and was conducted in accordance with the China Good Clinical Practice in Research guidelines. Results: A significant difference in body mass index (BMI) was observed between the healthy group and acute pancreatitis (AP) patients (p < 0.05), with a more pronounced disparity noted in cases of hyperlipidemic acute pancreatitis (p < 0.01). A potential risk for AP was identified at a BMI greater than 23.56 kg/m2 (AUC = 0.6086, p < 0.05). Being in the obese stage I (95%CI, [1.11-1.84]) or having a BMI below 25.4 kg/m2 (95%CI, [1.82-6.48]) are identified as risk factors for adverse AP progression. Moreover, BMI effectively predicts the onset of acute edematous pancreatitis and acute necrotizing pancreatitis (AUC = 0.7893, p < 0.001, cut-off value = 25.88 kg/m2). A higher BMI correlates with increased recurrence rates within a short timeframe (r = 0.7532, p < 0.01). Conclusions: Elevated BMI is a risk factor for both the occurrence and progression of AP, and underweight status may similarly contribute to poor disease outcomes. BMI is crucial for risk prediction and stratification in AP and warrants ongoing monitoring and consideration.


Subject(s)
Pancreatitis , Humans , Pancreatitis/diagnosis , Retrospective Studies , Body Mass Index , Acute Disease , Clinical Relevance , Severity of Illness Index
4.
Sci Adv ; 10(4): eadj5640, 2024 Jan 26.
Article in English | MEDLINE | ID: mdl-38266093

ABSTRACT

The extent to which AIRRs differ among and within individuals remains elusive. Via ultra-deep repertoire sequencing of 22 and 25 tissues in three cynomolgus macaques, respectively, we identified 84 and 114 novel IGHV and TRBV alleles, confirming 72 (85.71%) and 100 (87.72%) of them. The heterogeneous V gene usage patterns were influenced, in turn, by genetics, isotype (for BCRs only), tissue group, and tissue. A higher proportion of intragroup shared clones in the intestinal tissues than those in other tissues suggests a close intra-intestinal adaptive immunity network. Significantly higher mutation burdens in the public clones and the inter-tissue shared IgM and IgD clones indicate that they might target the shared antigens. This study reveals the extensive heterogeneity of the AIRRs at various levels and has broad fundamental and clinical implications. The data generated here will serve as an invaluable resource for future studies on adaptive immunity in health and diseases.


Subject(s)
Adaptive Immunity , Immunoglobulin Isotypes , Animals , Adaptive Immunity/genetics , Alleles , Macaca fascicularis/genetics , Receptors, Immunologic
5.
Sci Total Environ ; 912: 169464, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38123082

ABSTRACT

No field study has provided a detailed characterization of the molecular composition and spatial distribution of a vadose zone plume of petroleum volatile organic compounds (VOCs), which is critical to improve the current understanding of petroleum VOC transport and fate. This is study reports a high-resolution analysis of two distinct vapor plumes emanating from two different light non-aqueous phase liquid (LNAPL) sources (an aliphatic-rich LNAPL for Zone #1vs an aromatic-rich LNAPL for Zone #2) at a large petrochemical site. Although deep soil vapor signatures were similar to the source zone LNAPL signatures, the composition of the shallow soil vapors reflected preferential attenuation of certain hydrocarbons over others during upward transport in the vadose zone. Between deeper and shallower soil gas samples, attenuation of aromatics was observed under all conditions, but important differences were observed in attenuation to aliphatic compound classes. Attenuation of all aliphatic compounds was observed under aerobic conditions but little attenuation of any aliphatics was observed under anoxic conditions without methane. In contrast, under methanogenic conditions, paraffins attenuated more than isoparaffins and naphthenes. These results suggest that isoparafins and naphthenes may present more of a vapor intrusion risk than benzene or other aromatic hydrocarbons commonly considered to be petroleum vapor intrusion risk drivers. While the overall vapor composition changed significantly within the vadose zone, diagnostic ratios of relatively recalcitrant alkylcyclopentanes were preserved in shallow soil vapor samples. These alkylcyclopentanes may be useful for distinguishing between petroleum vapor intrusion and other sources of petroleum VOCs detected in indoor air.

6.
J Am Chem Soc ; 145(49): 26833-26842, 2023 Dec 13.
Article in English | MEDLINE | ID: mdl-38039190

ABSTRACT

Halogen substitution has been proven as an effective approach to the band gap engineering and optoelectronic modulation of organic-inorganic hybrid metal halide (OIHMH) materials. Various high-performance mixed halide OIHMH film materials have been primarily obtained through the substitution of coordinated halogens in their inorganic octahedra. Herein, we propose a new strategy of substitution of free halogen outside the inorganic octahedra for constructing mixed halide OIHMH single crystals with chiral structures, resulting in a boost of their linear and nonlinear chiroptical properties. The substitution from DMA4[InCl6]Cl (DMA = dimethylammonium) to DMA4[InCl6]Br crystals through a facile antisolvent vaporization method produces centimeter-scale single crystals with high thermal stability along with high quantum yield photoluminescence, conspicuous circularly polarized luminescence, and greatly enhanced second harmonic generation (SHG). In particular, the obtained DMA4[InCl6]Br single crystal features an intrinsic chiral structure, exhibiting a significant SHG circular dichroism (SHG-CD) response with a highest reported anisotropy factor (gSHG-CD) of 1.56 among chiral OIHMH materials. The enhancements in both linear and nonlinear chiroptical properties are directly attributed to the modulation of octahedral distortion. The mixed halide OIHMH single crystals obtained by free halogen substitution confine the introduced halogens within free halogen sites of the lattice, thereby ensuring the stability of compositions and properties. The successful employment of such a free halogen substitution approach may broaden the horizon of the regulation of structures and the optoelectronic properties of the OIHMH materials.

7.
Biomater Adv ; 154: 213640, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37804684

ABSTRACT

Diabetic complications with high-glucose status (HGS) cause the dysregulated autophagy and excessive apoptosis of multiple-type cells, leading to the difficulty in wound self-healing. Herein, we firstly developed fiber-reinforced gelatin (GEL)/ß-cyclodextrin (ß-CD) therapeutic hydrogels by the modification of platelet-rich plasma exosomes (PRP-EXOs). The GEL fibers that were uniformly dispersed within the GEL/ß-CD hydrogels remarkably enhanced the compression strengths and viscoelasticity. The PRP-EXOs were encapsulated in the hydrogels via the covalent crosslinking between the PRP-EXOs and genipin. The diabetic rat models demonstrated that the GEL/ß-CD hydrogels and PRP-EXOs cooperatively promoted diabetic wound healing. On the one hand, the GEL/ß-CD hydrogels provided the biocompatible microenvironments and active components for cell adhesion, proliferation and skin tissue regeneration. On the other hand, the PRP-EXOs in the therapeutic hydrogels significantly activated the autophagy and inhibited the apoptosis of human umbilical vein endothelial cells (HUVECs) and human skin fibroblasts (HSFs). The activation of autophagy and inhibition of apoptosis in HUVECs and HSFs induced the blood vessel creation, collagen formation and re-epithelialization. Taken together, this work proved that the incorporation of PRP-EXOs in a wound dressing was an effective strategy to regulate autophagy and apoptosis, and provide a novel therapeutic platform for diabetic wound healing.


Subject(s)
Diabetes Complications , Diabetes Mellitus , Exosomes , Platelet-Rich Plasma , Rats , Humans , Animals , Hydrogels/pharmacology , Gelatin/pharmacology , Exosomes/metabolism , Wound Healing , Diabetes Complications/metabolism , Human Umbilical Vein Endothelial Cells , Platelet-Rich Plasma/metabolism , Diabetes Mellitus/metabolism
8.
Toxicol Appl Pharmacol ; 479: 116713, 2023 11 15.
Article in English | MEDLINE | ID: mdl-37838222

ABSTRACT

BACKGROUND: Doxorubicin (DOX)-induced cardiotoxicity is an important cause of poor prognosis in cancer patients treated with DOX. Angiotensin IV (Ang IV) has multiple protective effects against cardiovascular diseases, including diabetic cardiomyopathy and myocardial infarction, but its role in DOX-induced cardiotoxicity is currently unclear. In this study, we investigated the effects of Ang IV on DOX-induced cardiotoxicity. METHODS: The viability of primary cardiomyocytes was measured by Cell Counting Kit-8 assays and Hoechst 33342/propidium iodide staining in vitro. ELISAs (serum cTnT and CK-MB) and echocardiography were performed to assess myocardial injury and cardiac function in vivo. Phalloidin staining, haematoxylin and eosin staining and wheat germ agglutinin staining were conducted to detect cardiomyocyte atrophy. We also performed C11 BODIPY staining, measured the levels of Ptgs2 and malondialdehyde and detected the concentrations of ferrous ions, glutathione and oxidized glutathione to indicate ferroptosis. RESULTS: Ang IV not only attenuated DOX-induced atrophy and cardiomyocyte injury in vitro but also alleviated myocardial injury and improved cardiac function in DOX-treated mice in vivo. Moreover, Ang IV reversed DOX-induced downregulation of glutathione peroxidase 4 (GPX4) and inhibited ferroptosis both in vitro and in vivo. Knockdown of GPX4 by siRNA abolished the cardioprotective effects of Ang IV. Furthermore, Ang IV increased GPX4 levels and ameliorated ferroptosis in RAS-selective lethal 3-treated primary cardiomyocytes. CONCLUSIONS: Ang IV ameliorates DOX-induced cardiotoxicity by upregulating GPX4 and inhibiting ferroptosis. Ang IV may be a promising candidate to protect against DOX-induced cardiotoxicity in the future.


Subject(s)
Cardiotoxicity , Ferroptosis , Mice , Humans , Animals , Cardiotoxicity/pathology , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Phospholipid Hydroperoxide Glutathione Peroxidase/pharmacology , Doxorubicin/adverse effects , Myocytes, Cardiac , Atrophy/chemically induced , Oxidative Stress , Apoptosis
9.
Chem Commun (Camb) ; 59(48): 7447-7450, 2023 Jun 13.
Article in English | MEDLINE | ID: mdl-37254664

ABSTRACT

Chiral hybrid metal halides have grabbed extensive attention in linear and nonlinear chiroptics. Herein, 0D chiral zinc halides, (R-/S-2-MP)ZnCl4, have been fabricated, which demonstrate high efficiency second-order nonlinear optical responses. Incorporating Sb3+ into the chiral zinc halide matrix triggers the circularly polarized luminescence effectively with a balance between quantum yield and luminescence dissymmetry factor.

10.
Int J Biol Macromol ; 226: 900-914, 2023 Jan 31.
Article in English | MEDLINE | ID: mdl-36502950

ABSTRACT

Diabetic skin disorders are lingering and refractory clinical diseases. In this study, a genipin-crosslinked porous chitosan fiber (CSF) hydrogel was fabricated to achieve rapid wound healing. By embedding clemastine fumarate (CF) in the CSF hydrogel pores, we synthesised a CSF/CF hydrogel for the treatment of diabetic wounds. The microstructure, chemical elements, spectral variation, mechanical properties, swelling ratios, degradability, and toxicity of the CSF/CF hydrogels were studied. Compared with the typical CS power hydrogel, the porous CSF hydrogel crosslinked with genipin possesses a stable structure and improved physicochemical properties. Moreover, CF was slowly released from the CSF hydrogel. Molecular simulation also showed that CF was evenly embedded inside the cavity formed by the novel CSF hydrogel. The results suggested that CF can resist damage from high glucose levels and promote proliferation, tube formation, and migration of endothelial cells (ECs) and fibroblasts. The CSF/CF hydrogel promoted wound healing in a rat model. Mechanistically, the beneficial effect of CF on wound healing may be related to activation of the MEK/ERK and PI3K/Akt signalling pathways. In conclusion, genipin-crosslinked CSF/CF hydrogel can accelerate wound healing and may be an effective therapeutic method for treating diabetic skin lesions.


Subject(s)
Chitosan , Diabetes Mellitus , Rats , Animals , Hydrogels/chemistry , Chitosan/chemistry , Clemastine/pharmacology , Endothelial Cells , Phosphatidylinositol 3-Kinases , Delayed-Action Preparations/pharmacology , Wound Healing , Biocompatible Materials/pharmacology
11.
Front Nutr ; 9: 1047029, 2022.
Article in English | MEDLINE | ID: mdl-36532547

ABSTRACT

Background: Muscle loss is a common characteristic of cancer-related malnutrition and a predictor of poorer prognosis in oncological patients. This study evaluated the association between altered body composition 6 months after surgery and the prognosis in patients with non-metastatic colorectal cancer. Materials and methods: A total of 314 patients who underwent elective curative surgery were enrolled in the study. The third lumbar CT images on preoperative and 6-months postoperative were collected to calculate the skeletal muscle index (SMI), visceral adiposity index (VATI), and subcutaneous adiposity index (SATI). Sarcopenia was defined by the cut-off values reported in the literature, and risk factors affecting overall survival (OS) and disease-free survival (DFS) in CRC were analyzed using Cox regression models. Results: Eighty-two of 314 patients (26.1%) with CRC were diagnosed with sarcopenia before surgery, the preoperative sarcopenia was not significantly associated with the prognosis of CRC patients. There were significant differences in frequency of complications between patient groups according to sarcopenia (41.5 vs. 21.4%, p = 0.004). The Postoperative LOS (11.21 ± 3.04 vs. 8.92 ± 2.84, p < 0.001) was longer in the sarcopenia group than in the non-sarcopenia group, and 30-d readmission (24.4 vs. 6.0%, p < 0.001) was higher in the sarcopenia group compared to the non-sarcopenia group. In multivariate analysis, 6-months SMI loss > 10% after surgery was independently associated with poorer OS [hazard ratio (HR) = 3.74; 95% confidence interval (CI) 1.96 to 7.12; P < 0.001] and DFS (HR = 3.33; 95% CI, 1.71 to 6.47; P < 0.001). SMI changes were moderately correlated with changes in body mass index (BMI) (R = 0.47, P < 0.001). Conclusion: 6-months muscle loss after surgery may affect overall and disease-free survival and was an independent predictor of prognosis in patients with CRC.

12.
Environ Pollut ; 310: 119881, 2022 Oct 01.
Article in English | MEDLINE | ID: mdl-35952988

ABSTRACT

The synthesis of clay-biochar composite has been recognized as an effective way to enhance the removal of pollutants. The interaction between clay mineral and biomass during thermal pyrolysis and the sorption capacity for ionic/nonionic organic containments have not been elaborated. In this study, two types of biochar were obtained from pyrolytic carbonization of the cellulosic-rich corn straw (C) and lignin-rich pine wood (P) at 500 or 700 °C. Typical clay minerals kaolinite and montmorillonite were selected to prepare clay-biochar composite. The results showed that the addition of clay mineral could strengthen dehydration reaction of corn straw biomass and reinforce its carbon structure. Montmorillonite-biochar composite owned more CC functional groups and porous structure than kaolinite-biochar composite. The addition of clay minerals could promote electrostatic attraction of ionic formed norfloxacin (NOR) on clay-pine wood biochar. However, the sorption capacity of nonionic diethyl phthalate (DEP) adsorption on clay-corn straw biochar decreased, owing to that clay increased the compactness of the biochar carbon structure, thus inhabited hydrophobic partition of nonionic organic compounds on disordered carbon fraction. The results from this study provide insights into the suitable contaminated site remediation by clay-biochar composite.


Subject(s)
Kaolin , Norfloxacin , Adsorption , Bentonite , Carbon , Charcoal , Clay , Ions , Minerals , Zea mays
13.
J Immunol ; 208(12): 2675-2685, 2022 06 15.
Article in English | MEDLINE | ID: mdl-35606050

ABSTRACT

The adaptive immune receptor repertoire consists of the entire set of an individual's BCRs and TCRs and is believed to contain a record of prior immune responses and the potential for future immunity. Analyses of TCR repertoires via deep learning (DL) methods have successfully diagnosed cancers and infectious diseases, including coronavirus disease 2019. However, few studies have used DL to analyze BCR repertoires. In this study, we collected IgG H chain Ab repertoires from 276 healthy control subjects and 326 patients with various infections. We then extracted a comprehensive feature set consisting of 10 subsets of repertoire-level features and 160 sequence-level features and tested whether these features can distinguish between infected individuals and healthy control subjects. Finally, we developed an ensemble DL model, namely, DL method for infection diagnosis (https://github.com/chenyuan0510/DeepID), and used this model to differentiate between the infected and healthy individuals. Four subsets of repertoire-level features and four sequence-level features were selected because of their excellent predictive performance. The DL method for infection diagnosis outperformed traditional machine learning methods in distinguishing between healthy and infected samples (area under the curve = 0.9883) and achieved a multiclassification accuracy of 0.9104. We also observed differences between the healthy and infected groups in V genes usage, clonal expansion, the complexity of reads within clone, the physical properties in the α region, and the local flexibility of the CDR3 amino acid sequence. Our results suggest that the Ab repertoire is a promising biomarker for the diagnosis of various infections.


Subject(s)
COVID-19 , Deep Learning , Amino Acid Sequence , COVID-19/diagnosis , Humans , Receptors, Antigen, T-Cell
14.
BMC Musculoskelet Disord ; 23(1): 67, 2022 Jan 18.
Article in English | MEDLINE | ID: mdl-35042504

ABSTRACT

OBJECTIVE: This study aimed to identify key diagnostic markers and immune infiltration of (SONFH) by bioinformatics analysis. METHODS: Related SONFH datasets were downloaded from the Gene Expression Omnibus (GEO) database. First, we identified the differentially expressed genes (DEGs) and performed the functional enrichment analysis. Then weighted correlation network analysis (WGCNA) and the MCODE plug-in in Cytoscape were used to identify the diagnostic markers of SONFH. Finally, CIBERSORT was used to analyze the immune infiltration between SONFH and healthy controls, and the correlation between infiltrating immune cells and diagnostic markers was analyzed. RESULTS: TYROBP, TLR2, P2RY13, TLR8, HCK, MNDA, and NCF2 may be key diagnostic markers of SONFH. Immune cell infiltration analysis revealed that Memory B cells and activated dendritic cells may be related to the SONFH process. Moreover, HCK was negatively correlated with CD8 T cells, and neutrophils were positively correlated with those key diagnostic markers. CONCLUSIONS: TYROBP, TLR2, P2RY13, TLR8, HCK, MNDA, and NCF2 may be used as diagnostic markers of SONFH, and immune-related mechanism of SONFH and the potential immunotherapy are worthy of further study.


Subject(s)
Femur Head , Osteonecrosis , Biomarkers , Computational Biology , Humans , Memory B Cells , Steroids
15.
BMC Musculoskelet Disord ; 23(1): 2, 2022 Jan 03.
Article in English | MEDLINE | ID: mdl-34980071

ABSTRACT

BACKGROUND: Accurate posterior column reduction remains a challenging and controversial topic in the management of complex pilon fractures (AO/OTA C3). We aim to report the outcomes of surgical treatment for 22 AO/OTA C3 pilon fracture cases between January 2015 and May 2017 and highlight some traps and tips. METHODS: Three patients underwent two-stage early plating on the posterior column through a posterolateral approach. The remaining 19 patients were treated with two-stage delayed plating on the posterior column: 11 patients were treated with a posterolateral approach, five patients with a modified posteromedial approach, and three patients with a single anterior approach. The reduction of the posterior column was evaluated according to the Burwell-Charnley's radiographic criteria, and functional outcomes were assessed using the American Orthopedic Foot and Ankle Society (AOFAS) scores. RESULTS: Posterior column malreduction occurred in five cases, including in one case that was re-adjusted immediately and in another case that was re-adjusted during a two-staged delayed operation. According to Burwell-Charnley's criteria, the satisfactory rate of fracture reduction was 81.8%. After 1 year, the mean AOFAS score was 81.9 (81.9 ± 9.9); the outcome was excellent in three (20.0%), good in nine (60.0%), and fair in three (20.0%). Excellent or good outcomes were noted in 12 patients (80.0%). CONCLUSIONS: The combined anterior and posterior approach is suggested in the second stage of plating so that the posterior column fragments can be re-adjusted intraoperatively, if necessary. Following these procedures, satisfactory reduction and recovery of good ankle function can be anticipated.


Subject(s)
Ankle Fractures , Tibial Fractures , Ankle Fractures/diagnostic imaging , Ankle Fractures/surgery , Ankle Joint , Fracture Fixation, Internal , Humans , Retrospective Studies , Tibial Fractures/diagnostic imaging , Tibial Fractures/surgery , Treatment Outcome
16.
Front Immunol ; 12: 739179, 2021.
Article in English | MEDLINE | ID: mdl-34764956

ABSTRACT

Detailed knowledge of the diverse immunoglobulin germline genes is critical for the study of humoral immunity. Hundreds of alleles have been discovered by analyzing antibody repertoire sequencing (Rep-seq or Ig-seq) data via multiple novel allele detection tools (NADTs). However, the performance of these NADTs through antibody sequences with intrinsic somatic hypermutations (SHMs) is unclear. Here, we developed a tool to simulate repertoires by integrating the full spectrum features of an antibody repertoire such as germline gene usage, junctional modification, position-specific SHM and clonal expansion based on 2152 high-quality datasets. We then systematically evaluated these NADTs using both simulated and genuine Ig-seq datasets. Finally, we applied these NADTs to 687 Ig-seq datasets and identified 43 novel allele candidates (NACs) using defined criteria. Twenty-five alleles were validated through findings of other sources. In addition to the NACs detected, our simulation tool, the results of our comparison, and the streamline of this process may benefit further humoral immunity studies via Ig-seq.


Subject(s)
Genes, Immunoglobulin , Genetic Variation , Genomics , High-Throughput Nucleotide Sequencing , Immunity, Humoral/genetics , Immunoglobulin G/genetics , Algorithms , Alleles , Computer Simulation , Databases, Genetic , Gene Library , Humans , Immunoglobulin G/immunology
17.
Front Immunol ; 12: 717496, 2021.
Article in English | MEDLINE | ID: mdl-34484220

ABSTRACT

The antibody repertoire is a critical component of the adaptive immune system and is believed to reflect an individual's immune history and current immune status. Delineating the antibody repertoire has advanced our understanding of humoral immunity, facilitated antibody discovery, and showed great potential for improving the diagnosis and treatment of disease. However, no tool to date has effectively integrated big Rep-seq data and prior knowledge of functional antibodies to elucidate the remarkably diverse antibody repertoire. We developed a Rep-seq dataset Analysis Platform with an Integrated antibody Database (RAPID; https://rapid.zzhlab.org/), a free and web-based tool that allows researchers to process and analyse Rep-seq datasets. RAPID consolidates 521 WHO-recognized therapeutic antibodies, 88,059 antigen- or disease-specific antibodies, and 306 million clones extracted from 2,449 human IGH Rep-seq datasets generated from individuals with 29 different health conditions. RAPID also integrates a standardized Rep-seq dataset analysis pipeline to enable users to upload and analyse their datasets. In the process, users can also select set of existing repertoires for comparison. RAPID automatically annotates clones based on integrated therapeutic and known antibodies, and users can easily query antibodies or repertoires based on sequence or optional keywords. With its powerful analysis functions and rich set of antibody and antibody repertoire information, RAPID will benefit researchers in adaptive immune studies.


Subject(s)
Antibodies/genetics , Computational Biology/methods , Databases, Genetic , Humans , Software , Web Browser
18.
J Genet Genomics ; 48(10): 936-945, 2021 10 20.
Article in English | MEDLINE | ID: mdl-34420911

ABSTRACT

The sequence upstream of the antibody variable region (antibody upstream sequence [AUS]) consists of a 5' untranslated region (5' UTR) and a preceding leader region. The sequence variations in AUS affect antibody engineering and PCR based antibody quantification and may also be implicated in mRNA transcription and translation. However, the diversity of AUSs remains elusive. Using 5' rapid amplification of cDNA ends and high-throughput antibody repertoire sequencing technique, we acquired full-length AUSs for human, rhesus macaque, cynomolgus macaque, mouse, and rat. We designed a bioinformatics pipeline and identified 3307 unique AUSs, corresponding to 3026 and 1457 unique sequences for 5' UTR and leader region, respectively. Comparative analysis indicated that 928 (63.69%) leader sequences are novel relative to those recorded in the international ImMunoGeneTics information system. Evolutionarily, leader sequences are more conserved than 5' UTR and seem to coevolve with their downstream V genes. Besides, single-nucleotide polymorphisms are position dependent for leader regions and may contribute to the functional reversal of the downstream V genes. Finally, the AUGs in AUSs were found to have little impact on gene expression. Taken together, our findings can facilitate primer design for capturing antibodies efficiently and provide a valuable resource for antibody engineering and molecule-level antibody studies.


Subject(s)
Macaca mulatta , Animals
19.
Cell Rep ; 35(6): 109110, 2021 05 11.
Article in English | MEDLINE | ID: mdl-33979623

ABSTRACT

Antibody repertoire sequencing enables researchers to acquire millions of B cell receptors and investigate these molecules at the single-nucleotide level. This power and resolution in studying humoral responses have led to its wide applications. However, most of these studies were conducted with a limited number of samples. Given the extraordinary diversity, assessment of these key features with a large sample set is demanded. Thus, we collect and systematically analyze 2,152 high-quality heavy-chain antibody repertoires. Our study reveals that 52 core variable genes universally contribute to more than 99% of each individual's repertoire; a distal interspersed preferences characterize V gene recombination; the number of public clones between two repertoires follows a linear model, and the positive selection dominates at RGYW motif in somatic hypermutations. Thus, this population-level analysis resolves some critical features of the antibody repertoire and may have significant value to the large cadre of scientists.


Subject(s)
Antibodies, Neoplasm/immunology , Biology/methods , High-Throughput Nucleotide Sequencing/methods , Receptors, Antigen, B-Cell/metabolism , V(D)J Recombination/immunology , Datasets as Topic , Humans
20.
Zhen Ci Yan Jiu ; 46(3): 248-53, 2021 Mar 25.
Article in Chinese | MEDLINE | ID: mdl-33798300

ABSTRACT

The concept of enhanced recovery after surgery (ERAS) is based on evidence-based medicine. By optimizing the treatment measures, the stress response of the body is reduced to meet the body's metabolic changes during the perioperative period, so as to achieve the purpose of accelerating recovery. In the perioperative period, acupuncture can relieve patients' preoperative anxiety, shorten fasting time, reduce the amount of anesthetics, protect organ function, reduce postoperative pain, reduce postoperative nausea and vomiting, and speed up postoperative recovery. The addition of acupuncture intervention in ERAS would provide newmethods and new ideas for the construction of ERAS. But at present, the application of acupuncture in ERAS has problems such as lacking of overall consideration and insufficient standardization, etc.


Subject(s)
Acupuncture Therapy , Acupuncture , Enhanced Recovery After Surgery , Acupuncture Points , Humans , Pain, Postoperative/etiology , Pain, Postoperative/therapy
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