Coil-to-globule transition by dissipative particle dynamics simulation

The dynamics of a collapsing polymer under a temperature quench in dilute solution is investigated by dissipative particles dynamics. Hydrodynamic interactions and many-body interaction are preserved naturally by incorporating explicit solvent particles in this approach. Our simulation suggests a four-stage collapse pathway: localized clusters formation, cluster coarsening in situ, coarsening involving global backbone conformation change into a crumpled globule, and compaction of the globule. For all the quench depths and chain lengths used in our study, collapse proceeds without the chain getting trapped in a metastable “sausage” configuration, as reported in some earlier studies. We obtain the time scales for each of the first three stages, as well as its scaling with the quench depths ξ and chain lengths N. The total collapse time scales as τ_c ~ ξ^(−0.46 ± 0.04)N^(0.98 ± 0.09), with the quench depth and degree of polymerization

The Contribution of Backbone Electrostatic Repulsion to DNA Mechanical Properties is Length-Scale-Dependent.

The mechanics of DNA bending is crucially related to many vital biological processes. Recent experiments reported anomalous flexibility for DNA on short length scales, calling into doubt the validity of the harmonic worm-like chain (WLC) model in this region. In the present work, we systematically probed the bending dynamics of DNA at different length scales. In contrast to the remarkable deviation from the WLC description for DNA duplexes of less than three helical turns, our atomistic studies indicate that the neutral "null isomer" behaves in accord with the ideal elastic WLC and exhibits a uniform decay for the directional correlation of local bending. The backbone neutralization weakens the anisotropy in the effective bending preference and the helical periodicity of bend correlation that have previously been observed for normal DNA. The contribution of electrostatic repulsion to stretching cooperativity and the mechanical properties of DNA strands is length-scale-dependent: the phosphate neutralization increases the stiffness of DNA below two helical turns, but it is decreased for longer strands. We find that DNA rigidity is largely determined by base pair stacking, with electrostatic interactions contributing only around 10% of the total persistence length

Shape-induced crystallization of binary DNA-functionalized nanocubes

Leveraging the anisotropic shape of DNA-functionalized nanoparticles holds potential for shape-directed crystallization of a wide collection of superlattice structures. Using coarse-grained molecular dynamics simulations, we study the self-assembly of a binary mixture of cubic gold nanoparticles, which are functionalized by complementary DNA strands. We observe the spontaneous self-assembly of simple cubic (SC), plastic body-centered tetragonal (pBCT), and compositionally disordered plastic body-centered tetragonal (d-pBCT) phases due to hybridization of the DNA strands. We systematically investigate the effect of length, grafting density, as well as rigidity of the DNA strands on the self-assembly behavior of cubic nanoparticles. We measure the potential of mean force between DNA-functionalized nanocubes for varying rigidity of the DNA strands and DNA lengths. Using free-energy calculations, we find that longer and flexible DNA strands can lead to a phase transformation from SC to the pBCT phase due to a gain in entropy arising from the orientational degrees of freedom of the nanocubes in the pBCT phase. Our results may serve as a guide for self-assembly experiments on DNA-functionalized cubic nanoparticles

The associations between gut microbiota and chronic respiratory diseases: a Mendelian randomization study

IntroductionGrowing evidence indicates that variations in the composition of the gut microbiota are linked to the onset and progression of chronic respiratory diseases (CRDs), albeit the causal relationship between the two remains unclear.MethodsWe conducted a comprehensive two-sample Mendelian randomization (MR) analysis to investigate the relationship between gut microbiota and five main CRDs, including chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), sarcoidosis, and pneumoconiosis. For MR analysis, the inverse variance weighted (IVW) method was utilized as the primary method. The MR–Egger, weighted median, and MR-PRESSO statistical methods were used as a supplement. To detect heterogeneity and pleiotropy, the Cochrane and Rucker Q test, MR–Egger intercept test, and MR-PRESSO global test were then implemented. The leave-one-out strategy was also applied to assess the consistency of the MR results.ResultsBased on substantial genetic data obtained from genome-wide association studies (GWAS) comprising 3,504,473 European participants, our study offers evidence that several gut microbial taxa, including 14 probable microbial taxa (specifically, 5, 3, 2, 3 and 1 for COPD, asthma, IPF, sarcoidosis, and pneumoconiosis, respectively) and 33 possible microbial taxa (specifically, 6, 7, 8, 7 and 5 for COPD, asthma, IPF, sarcoidosis, and pneumoconiosis, respectively) play significant roles in the formation of CRDs.DiscussionThis work implies causal relationships between the gut microbiota and CRDs, thereby shedding new light on the gut microbiota-mediated prevention of CRDs

A Nomogram for the Prediction of Prognosis in Patients With Distant Metastases of Nasopharyngeal Carcinoma

Background: Patients with metastatic nasopharyngeal carcinoma (NPC) have heterogeneous survival outcomes. This study aimed to establish an effective prognostic nomogram for patients with NPC with distant metastases using easily determined factors.Methods: The nomogram was based on a retrospective study of 103 patients with metastatic NPC at the First Affiliated Hospital of Xiamen University during January 2009–March 2016. Nomogram performance was evaluated using a concordance index (C-index) and assessed using calibration plot. Bootstraps with 1,000 resamples were applied to these analyses.Results: In univariate and multivariate Cox proportional hazards model analyses, chemotherapy, metastatic liver involvement, number of tumor metastases, N stage and derived neutrophil–lymphocyte ratio correlated with overall survival (OS). The recurrence probability calibration curve indicated good agreement between nomogram-based predictions and actual observations. For OS predictions, the nomogram had a C-index of 0.824 (95% confidence interval, 0.74–0.91). The stratification by nomogram score of patients into different subgroups showed significant distinction.Conclusion: This novel nomogram comprises factors that are easily determined at most hospitals and can predict survival in patients with distant metastases of NPC. This model can precisely estimate the survival of individual patients and identify subgroups of patients requiring specific therapeutic strategies

Nanodelivery of nucleic acids

Funding: This work was supported by the European Research Council (ERC) Starting Grant (ERC-StG-2019-848325 to J. Conde) and the Fundação para a Ciência e a Tecnologia FCT Grant (PTDC/BTM-MAT/4738/2020 to J. Conde). J.S. acknowledges US National Institute of Health (NIH) grants (R01CA200900, R01HL156362 and R01HL159012), the US DoD PRCRP Idea Award with Special Focus (W81XWH1910482), the Lung Cancer Discovery Award from the American Lung Association and the Innovation Discovery Grants award from the Mass General Brigham. H.L., D.Y. and X.Z. were supported by the National Key R&D Program of China (no. 2020YFA0710700), the National Natural Science Foundation of China (nos 21991132, 52003264, 52021002 and 52033010) and the Fundamental Research Funds for the Central Universities (no. WK2060000027).There is growing need for a safe, efficient, specific and non-pathogenic means for delivery of gene therapy materials. Nanomaterials for nucleic acid delivery offer an unprecedented opportunity to overcome these drawbacks; owing to their tunability with diverse physico-chemical properties, they can readily be functionalized with any type of biomolecules/moieties for selective targeting. Nucleic acid therapeutics such as antisense DNA, mRNA, small interfering RNA (siRNA) or microRNA (miRNA) have been widely explored to modulate DNA or RNA expression Strikingly, gene therapies combined with nanoscale delivery systems have broadened the therapeutic and biomedical applications of these molecules, such as bioanalysis, gene silencing, protein replacement and vaccines. Here, we overview how to design smart nucleic acid delivery methods, which provide functionality and efficacy in the layout of molecular diagnostics and therapeutic systems. It is crucial to outline some of the general design considerations of nucleic acid delivery nanoparticles, their extraordinary properties and the structure–function relationships of these nanomaterials with biological systems and diseased cells and tissues.publishersversionpublishe

Assessment of the reliability and quality of breast cancer related videos on TikTok and Bilibili: cross-sectional study in China

BackgroundAs the most common malignant tumor in the world, breast cancer also brings a huge disease burden to China. Ordinary people are increasingly inclined to use the Internet, especially video social platforms, as a source of health information. Educating the public to obtain correct information is important to reduce the incidence of breast cancer and improve the prognosis. However, the quality and reliability of breast cancer-related video content have not been fully studied.ObjectiveThis study aims to evaluate the quality of the information of breast cancer-related videos on TikTok and Bilibili video sharing platforms and factors related to video quality.MethodsWe collected the top 100 videos about breast cancer on TikTok and Bilibili, respectively. Categorize videos according to video source and video content. Video quality and reliability were assessed using Global Quality Score (GQS) and modified DISCERN (mDISCERN) tools. We also analyzed the correlation between video quality and video likes, comments, saves, and shares.ResultsAlthough the quality and reliability of Bilibili’s breast cancer videos were higher than TikTok (p = 0.002 and p = 0.001, respectively), the video quality of both video sharing platforms was not satisfactory, with a median GQS scores of 2.00 and 3.00 and mDISCERN scores of 1.00 and 2.00, respectively. In general, the quality and reliability of videos released by medical practitioners were higher than those of non-medical practitioners, and the quality and reliability of videos covering disease-related knowledge were higher than those of news reports (all p < 0.001). Among medical practitioners, the quality of videos uploaded by doctors in breast disease was significantly lower than that of doctors in other areas (p < 0.05). There was a significant positive correlation between video quality and duration (r = 0.240, p < 0.001), a weak negative correlation between video quality and likes (r = 0.191, p < 0.01), video quality and comments (r = 0.256, p < 0.001), video reliability and likes (r = 0.198, p < 0.001), video reliability and comments (r = 0.243, p < 0.01).ConclusionOur study shows that the quality and reliability of breast cancer-related videos on TikTok and Bilibili are poor, and the overall quality is unsatisfactory. But videos uploaded by medical practitioners covering disease knowledge, prevention and treatment are of higher quality. Medical practitioners are encouraged to publish more high-quality videos, while video social platforms should formulate relevant policies to censor and supervise health education videos, so as to enable the public to obtain reliable health information

Ternary hypervalent silicon hydrides via lithium at high pressure

Hydrogen is rarely observed as a ligand in hypervalent species, however, we find that high-pressure hydrogenation may stabilize hypervalent hydrogen-rich materials. Focusing on ternary silicon hydrides via lithium doping, we find anions composed of hypervalent silicon with H ligands formed under high pressure. Our results reveal two different hypervalent anions: layered SiH5− and tricapped triangular prismatic SiH62−. These differ from octahedral SiH62− described in earlier studies. In addition, there are further hydrogen-rich structures, Li3SiH10 and Li2SiH6+δ, which may be stabilized at high pressure. Our work provides pointers to future investigations on hydrogen-rich materials

Integrin αvβ3-targeted radionuclide therapy combined with immune checkpoint blockade immunotherapy synergistically enhances anti-tumor efficacy.

RATIONALE(#br)Radiotherapy combined with immunotherapy has revealed promising outcomes in both preclinical studies and ongoing clinical trials. Targeted radionuclide therapy (TRT) is a branch of radiotherapy concerned with the use of radioisotopes, radiolabeled molecules or nanoparticles that deliver particulate radiation to cancer cells. TRT is a promising approach in cases of metastatic disease where conventional treatments are no longer effective. The increasing use of TRT raises the question of how to best integrate TRT with immunotherapy. In this study, we proposed a novel therapeutic regimen that combined programmed death ligand 1 (PD-L1)-based immunotherapy with peptide-based TRT (177Lu as the radionuclide) in the murine colon cancer model.(#br)METHODS(#br)To explore the most appropriate timing of immunotherapy after radionuclide therapy, the anti-PD-L1 antibody (αPD-L1 mAb) was delivered in a concurrent or sequential manner when 177Lu TRT was given.(#br)RESULTS(#br)The results demonstrated that TRT led to an acute increase in PD-L1 expression on T cells, and TRT in combination with αPD-L1 mAb stimulated the infiltration of CD8+ T cells, which improved local tumor control, overall survival and protection against tumor rechallenge. Moreover, our data revealed that the time window for this combination therapy may be critical to outcome.(#br)CONCLUSIONS(#br)This therapeutic combination may be a promising approach to treating metastatic tumors in which TRT can be used. Clinical translation of the result would suggest that concurrent rather than sequential blockade of the PD-1/PD-L1 axis combined with TRT improves overall survival and long-term tumor control