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1.
Nature ; 580(7802): 245-251, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32269342

RESUMO

Radiologic screening of high-risk adults reduces lung-cancer-related mortality1,2; however, a small minority of eligible individuals undergo such screening in the United States3,4. The availability of blood-based tests could increase screening uptake. Here we introduce improvements to cancer personalized profiling by deep sequencing (CAPP-Seq)5, a method for the analysis of circulating tumour DNA (ctDNA), to better facilitate screening applications. We show that, although levels are very low in early-stage lung cancers, ctDNA is present prior to treatment in most patients and its presence is strongly prognostic. We also find that the majority of somatic mutations in the cell-free DNA (cfDNA) of patients with lung cancer and of risk-matched controls reflect clonal haematopoiesis and are non-recurrent. Compared with tumour-derived mutations, clonal haematopoiesis mutations occur on longer cfDNA fragments and lack mutational signatures that are associated with tobacco smoking. Integrating these findings with other molecular features, we develop and prospectively validate a machine-learning method termed 'lung cancer likelihood in plasma' (Lung-CLiP), which can robustly discriminate early-stage lung cancer patients from risk-matched controls. This approach achieves performance similar to that of tumour-informed ctDNA detection and enables tuning of assay specificity in order to facilitate distinct clinical applications. Our findings establish the potential of cfDNA for lung cancer screening and highlight the importance of risk-matching cases and controls in cfDNA-based screening studies.


Assuntos
DNA Tumoral Circulante/análise , DNA Tumoral Circulante/genética , Detecção Precoce de Câncer/métodos , Genoma Humano/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Mutação , Estudos de Coortes , Feminino , Hematopoese/genética , Humanos , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
2.
J Lipid Res ; 65(1): 100483, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38101620

RESUMO

Apolipoprotein H (APOH) downregulation can cause hepatic steatosis and gut microbiota dysbiosis. However, the mechanism by which APOH-regulated lipid metabolism contributes to metabolic dysfunction-associated steatotic liver disease (MASLD) remains undetermined. Herein, we aim to explore the regulatory effect of APOH, mediated through various pathways, on metabolic homeostasis and MASLD pathogenesis. We analyzed serum marker levels, liver histopathology, and cholesterol metabolism-related gene expression in global ApoH-/- C57BL/6 male mice. We used RNA sequencing and metabolomic techniques to investigate the association between liver metabolism and bacterial composition. Fifty-two differentially expressed genes were identified between ApoH-/- and WT mice. The mRNA levels of de novo lipogenesis genes were highly upregulated in ApoH-/- mice than in WT mice. Fatty acid, glycerophospholipid, sterol lipid, and triglyceride levels were elevated, while hyodeoxycholic acid levels were significantly reduced in the liver tissues of ApoH-/- mice than in those of WT mice. Microbial beta diversity was lower in ApoH-/- mice than in WT mice, and gut microbiota metabolic functions were activated in ApoH-/- mice. Moreover, ApoH transcripts were downregulated in patients with MASLD, and APOH-related differential genes were enriched in lipid metabolism. Open-source transcript-level data from human metabolic dysfunction-associated steatohepatitis livers reinforced a significant association between metabolic dysfunction-associated steatohepatitis and APOH downregulation. In conclusion, our studies demonstrated that APOH downregulation aggravates fatty liver and induces gut microbiota dysbiosis by dysregulating bile acids. Our findings offer a novel perspective on APOH-mediated lipid metabolic dysbiosis and provide a valuable framework for deciphering the role of APOH in fatty liver disease.


Assuntos
Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Humanos , Masculino , Camundongos , Animais , Metabolismo dos Lipídeos/genética , beta 2-Glicoproteína I/genética , beta 2-Glicoproteína I/metabolismo , beta 2-Glicoproteína I/farmacologia , Regulação para Baixo , Disbiose/metabolismo , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fígado/metabolismo , Ácidos Graxos/metabolismo
3.
Phys Rev Lett ; 132(24): 246503, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38949334

RESUMO

Novel critical phenomena beyond the Landau-Ginzburg-Wilson paradigm have been long sought after. Among many candidate scenarios, the deconfined quantum critical point (DQCP) constitutes the most fascinating one, and its lattice model realization has been debated over the past two decades. Here we apply the spherical Landau level regularization upon the exact (2+1)D SO(5) nonlinear sigma model with a topological term to study the potential DQCP therein. We perform a density matrix renormalization group (DMRG) simulation with SU(2)_{spin}×U(1)_{charge}×U(1)_{angular-momentum} symmetries explicitly implemented. Using crossing point analysis for the critical properties of the DMRG data, accompanied by quantum Monte Carlo simulations, we accurately obtain the comprehensive phase diagram of the model and find various novel quantum phases, including Néel, ferromagnet (FM), valence bond solid (VBS), valley polarized (VP) states and a gapless quantum disordered phase occupying an extended area of the phase diagram. The VBS-disorder and Néel-disorder transitions are continuous with non-Wilson-Fisher exponents. Our results show the VBS and Néel states are separated by either a weakly first-order transition or the disordered region with a multicritical point in between, thus opening up more interesting questions on the two-decade long debate on the nature of the DQCP.

4.
Phys Rev Lett ; 132(23): 236502, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38905653

RESUMO

Integer and fractional Chern insulators have been extensively explored in correlated flat band models. Recently, the prediction and experimental observation of fractional quantum anomalous Hall (FQAH) states with spontaneous time-reversal symmetry breaking have garnered attention. While the thermodynamics of integer quantum anomalous Hall (IQAH) states have been systematically studied, our theoretical knowledge on thermodynamic properties of FQAH states has been severely limited. Here, we delve into the general thermodynamic response and collective excitations of both IQAH and FQAH states within the paradigmatic flat Chern-band model with remote band considered. Our key findings include (i) in both ν=1 IQAH and ν=1/3 FQAH states, even without spin fluctuations, the charge-neutral collective excitations would lower the onset temperature of these topological states, to a value significantly smaller than the charge gap, due to band mixing and multiparticle scattering; (ii) by employing large-scale thermodynamic simulations in FQAH states in the presence of strong interband mixing between C=±1 bands, we find that the lowest collective excitations manifest as the zero-momentum excitons in the IQAH state, whereas in the FQAH state, they take the form of magnetorotons with finite momentum; (iii) the unique charge oscillations in FQAH states are exhibited with distinct experimental signatures, which we propose to detect in future experiments.

5.
Psychol Sci ; 35(3): 250-262, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38289294

RESUMO

Fundamental frequency ( fo) is the most perceptually salient vocal acoustic parameter, yet little is known about how its perceptual influence varies across societies. We examined how fo affects key social perceptions and how socioecological variables modulate these effects in 2,647 adult listeners sampled from 44 locations across 22 nations. Low male fo increased men's perceptions of formidability and prestige, especially in societies with higher homicide rates and greater relational mobility in which male intrasexual competition may be more intense and rapid identification of high-status competitors may be exigent. High female fo increased women's perceptions of flirtatiousness where relational mobility was lower and threats to mating relationships may be greater. These results indicate that the influence of fo on social perceptions depends on socioecological variables, including those related to competition for status and mates.


Assuntos
Voz , Adulto , Humanos , Masculino , Feminino , Homicídio , Percepção Social , Parceiros Sexuais
6.
Am J Obstet Gynecol ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38969199

RESUMO

BACKGROUND: While the phenotypic association between anti-Müllerian hormone (AMH) and age at menopause has been widely studied, the role of AMH in predicting the age at menopause is currently controversial, and the genetic architecture or causal relationships underlying these two traits is not well understood. AIM: We aimed to explore the shared genetic architecture between AMH and age at menopause, to identify shared pleiotropic loci and genes, and to investigate causal association and potential causal mediators. STUDY DESIGN: Using summary statistics from publicly available genome-wide association studies on AMH (N=7,049) and age at menopause (N=201,323) in Europeans, we investigated the global genetic architecture between AMH and age at menopause through linkage disequilibrium score regression. We employed pleiotropic analysis under composite null hypothesis (PLACO), Functional Mapping and Annotation of Genetic Associations (FUMA), Multimarker analysis of GenoMic annotation (MAGMA), and colocalization analysis to identify loci and genes with pleiotropic effects. Tissue enrichment analysis based on GTEx data was conducted using the Linkage Disequilibrium Score for the specific expression of genes analysis (LDSC-SEG). Functional genes that were shared were additionally identified through summary data-based Mendelian randomization (SMR). The relationship between AMH and age at menopause was examined through two-sample Mendelian randomization (MR), and potential mediators were further explored using colocalization and metabolite-mediated analysis. RESULTS: A positive genetic association (correlation coefficient = 0.88, P = 1.33 × 10-5) was observed between AMH and age at menopause. By using PLACO and FUMA, 42 significant pleiotropic loci were identified that were associated with AMH and age at menopause, and ten of these (rs10734411, rs61913600, rs2277339, rs75770066, rs28416520, rs9796, rs11668344, rs403727, rs6011452, and rs62237617) had colocalized loci. Additionally, 245 significant pleiotropic genes were identified by MAGMA. Genetic associations between AMH and age at menopause were markedly concentrated in various tissues including whole blood, brain, heart, liver, muscle, pancreas, and kidneys. Further, SMR analysis revealed nine genes that may have a causative effect on both AMH and age at menopause. A potential causal effect of age at menopause on AMH was suggested by two-sample MR analysis, with very-low-density lipoprotein identified as a potential mediator. CONCLUSIONS: Our study revealed a shared genetic architecture between AMH and age at menopause, providing a basis for experimental investigations and individual therapies to enhance reproductive outcomes. Furthermore, our findings emphasized that relying solely on AMH is not sufficient for accurately predicting the age at menopause, and a combination of other factors needs to be considered. Exploring new therapeutics aimed at delaying at the onset of menopause holds promise, particularly when targeting shared genes based on their shared genetic architecture.

7.
Analyst ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38984809

RESUMO

In this work, Au/Bi2O3 was synthesized by loading Au nanoparticles (NPs) onto ß-Bi2O3 by a simple solution reduction method. ß-Bi2O3 was synthesized by a precipitation-thermal decomposition procedure, which results in significantly improved SERS detection limits down to 10-9 M for methylene blue (MB) and 10-7 M for methyl orange (MO) as probe molecules, comparable to those reported for the best semiconductor SERS substrates. In particular, further deposition of Au NPs (5.20% wt%) onto ß-Bi2O3 results in a two-order-of-magnitude enhancement in detection sensitivity, achieving a detection limit of 10-11 M for MB and 10-9 M for MO. Under ultraviolet/visible irradiation, the Au/Bi2O3 hybrids substrate exhibits superior self-cleaning ability due to its photocatalytic degradation ability which can be applied repeatedly to the detection of pollutants. The advanced composite substrate simultaneously achieved ultra-low mass loading of Au NPs, outstanding detection performance, good reproducibility, high stability and self-cleaning ability. The development strategy of low load noble metal coupled high performance semiconductor ß-Bi2O3 to obtain nano-hybrid materials provides a method to balance SERS sensitivity, cost effectiveness and operational stability, and can be synthesized in large quantities, which is a key step towards commercialization and has good reliability prospects.

8.
Soc Psychiatry Psychiatr Epidemiol ; 59(4): 681-694, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37195293

RESUMO

PURPOSE: The prevalence of parental burnout, a condition that has severe consequences for both parents and children, varies dramatically across countries and is highest in Western countries characterized by high individualism. METHOD: In this study, we examined the mediators of the relationship between individualism measured at the country level and parental burnout measured at the individual level in 36 countries (16,059 parents). RESULTS: The results revealed three mediating mechanisms, that is, self-discrepancies between socially prescribed and actual parental selves, high agency and self-directed socialization goals, and low parental task sharing, by which individualism leads to an increased risk of burnout among parents. CONCLUSION: The results confirm that the three mediators under consideration are all involved, and that mediation was higher for self-discrepancies between socially prescribed and actual parental selves, then parental task sharing, and lastly self-directed socialization goals. The results provide some important indications of how to prevent parental burnout at the societal level in Western countries.


Assuntos
Esgotamento Profissional , Pais , Criança , Humanos , Esgotamento Psicológico , Socialização , Esgotamento Profissional/epidemiologia
9.
J Res Adolesc ; 34(2): 395-409, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38480475

RESUMO

Adolescents' family obligation is a cultural strength that shows enduring prevalence in China. Given that the meaning of family obligation has undergone rapid changes in recent decades, it is crucial to examine the role of family obligation in adolescent adjustment in contemporary China. More importantly, although past research has investigated the consequences of family obligation on adolescents' adjustment, little is known about the antecedents of Chinese adolescents' family obligation. Using a two-wave longitudinal sample of 450 Chinese adolescents (mean age = 13.78 years, SD = .71 years; 49% female) and their parents, the current research explored two questions. First, this study examined the role of family obligation in adolescents' academic achievement, externalizing problems, and internalizing problems over early adolescence. Second, this study explored the role of parents in predicting Chinese adolescents' family obligation, specifically whether parental expectations or parental acceptance was predictive of adolescents' family obligation over time. Third, this study investigated whether family obligation is an underlying mechanism between parenting and Chinese adolescents' adjustment. Results showed that Chinese adolescents' family obligation was longitudinally associated with increased academic achievement and reduced externalizing problems. Moreover, perceived parental acceptance, but not parental expectations, was longitudinally associated with Chinese adolescents' greater family obligation. Notably, family obligation mediated the longitudinal effect of parental acceptance on Chinese adolescents' externalizing problems. By studying both the consequences and antecedents of Chinese adolescents' family obligation, this study helps provide a comprehensive understanding of this cultural strength.


Assuntos
Relações Pais-Filho , Poder Familiar , Humanos , Feminino , Adolescente , Masculino , China/epidemiologia , Estudos Longitudinais , Relações Pais-Filho/etnologia , Poder Familiar/psicologia , Comportamento do Adolescente/psicologia , Sucesso Acadêmico , Pais/psicologia , População do Leste Asiático
10.
Proteins ; 91(3): 354-362, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36196751

RESUMO

Cysteinyl-tRNA synthetase (CysRS) catalyzes the aminoacylation reaction of cysteine to its cognate tRNACys in the first step of protein translation. It is found that CysRS is different from other aaRSs as it transfers cysteine without the need for an editing reaction, which is not applicable in the case of serine despite the similarity in their structures. Surprisingly, the reasons why CysRS has high amino acid specificity are not clear yet. In this research, the binding configurations of Cys-AMP and its near-cognate amino acid Ser-AMP with CysRS are compared by Molecular Dynamics (MD). The results reveal that CysRS screens the substrate Cys-AMP to a certain extent in the process of combination and recognition, thus providing a guarantee for the high selectivity of the next reaction. While Ser-AMP is in a folded state in CysRS. In the meanwhile, the interaction between Cys-AMP and Zn963 in CysRS is much stronger than Ser-AMP. The substrate-assisted aminoacylation mechanism in CysRS is also explored by Quantum Mechanics/Molecular Mechanics (QM/MM) modeling. According to the QM/MM potential energies, the energy barrier of TSCys-AMP is 91.75 kJ/mol, while that of TSSer-AMP is close to 150 kJ/mol. Based on thermochemistry calculations, it is found that the product of Cys-AMP is more stable than the reactant. In contrast, Ser-AMP has a reactant that is more stable than its product. As a result, it reflects that the specificity of CysRS originates from both the kinetic and thermodynamical perspectives of the reaction. Our investigations demonstrate comprehensively on how CysRS recognizes and catalyzes the substrate Cys-AMP, hoping to provide some guidance for researchers in this area.


Assuntos
Aminoacil-tRNA Sintetases , Simulação de Dinâmica Molecular , Cisteína , Aminoacil-tRNA Sintetases/química , Aminoacil-tRNA Sintetases/genética , Aminoacil-tRNA Sintetases/metabolismo , Aminoácidos/química , Especificidade por Substrato
11.
Anal Chem ; 95(30): 11273-11279, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37478050

RESUMO

Dopamine (DA) is an important neurotransmitter, which not only participates in the regulation of neural processes but also plays critical roles in tumor progression and immunity. However, direct identification of DA-containing exosomes, as well as quantification of DA in single vesicles, is still challenging. Here, we report a nanopipette-assisted method to detect single exosomes and their dopamine contents via amperometric measurement. The resistive-pulse current measured can simultaneously provide accurate information of vesicle translocation and DA contents in single exosomes. Accordingly, DA-containing exosomes secreted from HeLa and PC12 cells under different treatment modes successfully detected the DA encapsulation efficiency and the amount of exosome secretion that distinguish between cell types. Furthermore, a custom machine learning model was constructed to classify the exosome signals from different sources, with an accuracy of more than 99%. Our strategy offers a useful tool for investigating single exosomes and their DA contents, which facilitates the analysis of DA-containing exosomes derived from other untreated or stimulated cells and may open up a new insight to the research of DA biology.

12.
Phys Rev Lett ; 130(22): 226502, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37327445

RESUMO

Accurate simulations of the two-dimensional (2D) Hubbard model constitute one of the most challenging problems in condensed matter and quantum physics. Here we develop a tangent space tensor renormalization group (tanTRG) approach for the calculations of the 2D Hubbard model at finite temperature. An optimal evolution of the density operator is achieved in tanTRG with a mild O(D^{3}) complexity, where the bond dimension D controls the accuracy. With the tanTRG approach we boost the low-temperature calculations of large-scale 2D Hubbard systems on up to a width-8 cylinder and 10×10 square lattice. For the half-filled Hubbard model, the obtained results are in excellent agreement with those of determinant quantum Monte Carlo (DQMC). Moreover, tanTRG can be used to explore the low-temperature, finite-doping regime inaccessible for DQMC. The calculated charge compressibility and Matsubara Green's function are found to reflect the strange metal and pseudogap behaviors, respectively. The superconductive pairing susceptibility is computed down to a low temperature of approximately 1/24 of the hopping energy, where we find d-wave pairing responses are most significant near the optimal doping. Equipped with the tangent-space technique, tanTRG constitutes a well-controlled, highly efficient and accurate tensor network method for strongly correlated 2D lattice models at finite temperature.


Assuntos
Temperatura Baixa , Física , Método de Monte Carlo , Temperatura
13.
Phys Rev Lett ; 130(1): 016401, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36669223

RESUMO

While the ground-state phase diagram of the correlated flat-band systems has been intensively investigated, the dynamic and thermodynamic properties of such lattice models are less explored, but it is the latter which is most relevant to the experimental probes (transport, quantum capacitance, and spectroscopy) of the quantum moiré materials such as twisted bilayer graphene. Here we show, by means of momentum-space quantum Monte Carlo and exact diagonalization, in chiral limit there exists a unique thermodynamic characteristic for the correlated flat-band model with interaction-driven quantum anomalous Hall (QAH) ground state, namely, the transition from the QAH insulator to the metallic state takes place at a much lower temperature compared with the zero-temperature single-particle gap generated by the long-range Coulomb interaction. Such low transition temperature comes from the proliferation of excitonic particle-hole excitations, which transfers the electrons across the gap between different topological bands to restore the broken time-reversal symmetry and gives rise to a pronounced enhancement in the charge compressibility. Future experiments, to verify such generic thermodynamic characteristics, are proposed.


Assuntos
Temperatura Baixa , Elétrons , Termodinâmica , Temperatura , Método de Monte Carlo
14.
Phys Rev Lett ; 130(26): 266501, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37450825

RESUMO

The fermion disorder operator has been shown to reveal the entanglement information in 1D Luttinger liquids and 2D free and interacting Fermi and non-Fermi liquids emerging at quantum critical points (QCPs) [W. Jiang et al., arXiv:2209.07103]. Here we study, by means of large-scale quantum Monte Carlo simulation, the scaling behavior of the disorder operator in correlated Dirac systems. We first demonstrate the logarithmic scaling behavior of the disorder operator at the Gross-Neveu (GN) chiral Ising and Heisenberg QCPs, where consistent conformal field theory (CFT) content of the GN-QCP in its coefficient is found. Then we study a 2D monopole-free deconfined quantum critical point (DQCP) realized between a quantum-spin Hall insulator and a superconductor. Our data point to negative values of the logarithmic coefficients such that the DQCP does not correspond to a unitary CFT. Density matrix renormalization group calculations of the disorder operator on a 1D DQCP model also detect emergent continuous symmetries.


Assuntos
Simulação por Computador , Método de Monte Carlo
15.
Artigo em Inglês | MEDLINE | ID: mdl-36920986

RESUMO

A Gram-stain-positive, rod-shaped, non-spore-forming, catalase-negative, urease-negative, homofermentative and facultatively anaerobic strain, named WILCCON 0076T, was isolated from a wild ferment of pieces of a 'Kampung' durian fruit collected on the island of Ubin (Pulau Ubin), Singapore. The durian had fallen to the ground from a durian tree (Durio zibethinus), on which a group of long-tailed macaques had been observed picking and eating the fruits. Comparative analyses of 16S rRNA gene sequences indicated that WILCCON 0076T potentially represented a novel species within the genus Ligilactobacillus, with the most closely related type strain being Ligilactobacillus agilis DSM 20509T (16S rRNA gene sequence similarity of 97.2 %). Average nucleotide identity and digital DNA-DNA hybridization prediction values were only 86.0% and 18.9 %, respectively. On the basis of the results of a polyphasic approach that included phylogenomic, chemotaxonomic and morphological analyses, we propose a novel species with the name Ligilactobacillus ubinensis sp. nov. (type strain WILCCON 0076T=DSM 114293T=LMG 32698T).


Assuntos
Bombacaceae , Ácidos Graxos , Ácidos Graxos/química , Frutas , Análise de Sequência de DNA , RNA Ribossômico 16S/genética , Filogenia , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , Composição de Bases , Hibridização de Ácido Nucleico
16.
Analyst ; 148(3): 507-511, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36594781

RESUMO

Here, hydrophilic carbon dots (H-CDs) are prepared by a facile room temperature method. The strength of hydrogen bonds can be controlled by introducing proton and aprotic solvents, respectively, so as to realize the tunable aggregation state of H-CDs. Because of the ultrasensitive response to dimethyl sulfoxide (DMSO), H-CDs can serve as optical probes for detecting DMSO in a linear range of 0.005% to 0.75% and with a detection limit of 0.001%.

17.
Nature ; 543(7647): 723-727, 2017 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-28329770

RESUMO

Cancer somatic mutations can generate neoantigens that distinguish malignant from normal cells. However, the personalized identification and validation of neoantigens remains a major challenge. Here we discover neoantigens in human mantle-cell lymphomas by using an integrated genomic and proteomic strategy that interrogates tumour antigen peptides presented by major histocompatibility complex (MHC) class I and class II molecules. We applied this approach to systematically characterize MHC ligands from 17 patients. Remarkably, all discovered neoantigenic peptides were exclusively derived from the lymphoma immunoglobulin heavy- or light-chain variable regions. Although we identified MHC presentation of private polymorphic germline alleles, no mutated peptides were recovered from non-immunoglobulin somatically mutated genes. Somatic mutations within the immunoglobulin variable region were almost exclusively presented by MHC class II. We isolated circulating CD4+ T cells specific for immunoglobulin-derived neoantigens and found these cells could mediate killing of autologous lymphoma cells. These results demonstrate that an integrative approach combining MHC isolation, peptide identification, and exome sequencing is an effective platform to uncover tumour neoantigens. Application of this strategy to human lymphoma implicates immunoglobulin neoantigens as targets for lymphoma immunotherapy.


Assuntos
Apresentação de Antígeno/imunologia , Antígenos de Neoplasias/imunologia , Região Variável de Imunoglobulina/imunologia , Linfoma de Célula do Manto/imunologia , Antígenos de Neoplasias/química , Antígenos de Neoplasias/genética , Linfócitos T CD4-Positivos/imunologia , Citotoxicidade Imunológica , Análise Mutacional de DNA , Epitopos de Linfócito T/imunologia , Exoma/genética , Genômica , Antígenos HLA-D/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Região Variável de Imunoglobulina/química , Região Variável de Imunoglobulina/genética , Imunoterapia/tendências , Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/patologia , Linfoma de Célula do Manto/terapia , Mutação , Proteômica
18.
Appl Microbiol Biotechnol ; 107(21): 6507-6525, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37658164

RESUMO

Engineering Taq DNA polymerase (TaqPol) for improved activity, stability and sensitivity was critical for its wide applications. Multiple sequence alignment (MSA) has been widely used in engineering enzymes for improved properties. Here, we first designed TaqPol mutations based on MSA of 2756 sequences from both thermophilic and non-thermophilic organisms. Two double mutations were generated including a variant H676F/R677G showing a decrease in both activity and stability, and a variant Y686R/E687K showing an improved activity, but a decreased stability. Mutations targeted on coevolutionary residues of Arg677 and Tyr686 were then applied to rescue stability or activity loss of the double mutants, which achieved a partial success. Sequence analysis revealed that the two mutations are abundant in non-thermophilic sequences but not in thermophilic homologues. Then, a small-scale MSA containing sequences from only thermophilic organisms was applied to predict 13 single variants and two of them, E507Q and E734N showed a simultaneous increase in both stability and activity, even in sensitivity. A customized MSA was hence more effective in engineering a thermophilic enzyme and could be used in engineering other enzymes. Molecular dynamics simulations revealed the impact of mutations on the protein dynamics and interactions between TaqPol and substrates. KEY POINTS: • The pool of sequence for alignment is critical to engineering Taq DNA polymerase. • The variants with low properties can be rescued by mutations in coevolving network. • Improving binding with DNA can improve DNA polymerase stability and activity.

19.
Child Dev ; 94(1): 288-302, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36222063

RESUMO

This longitudinal study examined the reciprocal associations between paternal and maternal rejection and firstborn children's (Mage  = 49.9 months; 55% boys) behavior problems across the transition to siblinghood in a sample of 120 families recruited from 2016 to 2018 from Shanghai, China. Parental rejection and behavior problems were assessed before (prenatal) and 1, 6, and 12 months after the birth of a baby sibling. Random intercept cross-lagged panel models revealed positive relations between internalizing problems and both maternal and paternal rejection, and between externalizing problems and paternal rejection at the between-person level (rs = .32-.37), but only cross-lagged effects from children's internalizing and externalizing problems to maternal rejection at the within-person level (ßs = .30-.54).


Assuntos
População do Leste Asiático , Pai , Masculino , Feminino , Gravidez , Humanos , Criança , Pré-Escolar , Estudos Longitudinais , China , Pais
20.
Arch Womens Ment Health ; 26(4): 503-511, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37300569

RESUMO

PURPOSE: Parental burnout is a psychological syndrome that develops in response to the chronic stressors in one's role as a parent. It can be detrimental to the health and wellbeing of both parents and children and has been empirically proven to result in more negative parenting behaviours. Based on recent research, parental burnout is more prevalent in individualistic cultures. Considering that parenting norms and practices vary greatly across cultures, there could be different effects of parental burnout on parenting practices in different areas. The present study aimed to determine the relationship between parental burnout and parenting behaviours in Shanghai and Nanning, two cities in China that differ in the extent to which they have been exposed to the cultural influence of Western individualism, and to examine the moderating effect of city on these relationship patterns. METHODS: Three hundred and sixty-eight mothers in Shanghai and 180 mothers in Nanning took part in the survey. RESULTS: On average, mothers in Shanghai had more severe parental burnout than their counterparts in Nanning. Furthermore, parental burnout was associated with positive parenting behaviours (i.e., parental warmth) and negative parenting behaviours (i.e., parental hostility and neglect), and the associations between parental burnout and negative parenting behaviours in Nanning were greater than in Shanghai. CONCLUSIONS: These results can be explained by cultural differences in individualism and collectivism between Shanghai and Nanning. This study extends the knowledge on the role of culture in shaping parental roles.


Assuntos
Esgotamento Psicológico , Mães , Poder Familiar , Feminino , Humanos , Esgotamento Psicológico/epidemiologia , China/epidemiologia , Cidades , População do Leste Asiático , Mães/psicologia , Poder Familiar/psicologia , Pais/psicologia
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