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The source region of the Yellow River (SRYR) located in the northeast of the Qinghai-Tibetan Plateau is not only the largest runoff-producing area in the Yellow River Basin, but also the most important freshwater-supply ecological function area in China. In this study, the short-term spatiotemporal distribution of selected legacy and alternative perfluoroalkyl acids (PFAAs) in the SRYR was first investigated in multiple environmental media. Total PFAA concentrations were in the range of 1.16-14.3 ng/L, 4.25-42.1 pg/L, and 0.21-13.0 pg/g dw in rainwater, surface water, and sediment, respectively. C4-C7 PFAAs were predominant in various environmental matrices. Spatiotemporal characteristics were observed in the concentrations and composition profiles. Particularly, the spatial distribution of rainwater and the temporal distribution of surface water exhibited highly significant differences (p<0.01). Indian monsoon, westerly air masses, and local mountain-valley breeze were the driving factors that contributed to the change of rainwater. Rainwater, meltwater runoff, and precursor degradation were important sources of PFAA pollution in surface water. Organic carbon content was a major factor influencing PFAA distribution in sediment. These results provide a theoretical basis for revealing the regional transport and fate of PFAAs, and are also important prerequisites for effectively protecting the freshwater resource and aquatic environment of the Qinghai-Tibetan Plateau.
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A comprehensive analysis of spatial transcriptomics was carried out to better understand the progress of halo nevus. We found that halo nevus was characterized by overactive immune responses, triggered by chemokines and dendritic cells (DCs), T cells, and macrophages. Consequently, we observed abnormal cell death, such as apoptosis and disulfidptosis in halo nevus, some were closely related to immunity. Interestingly, we identified aberrant metabolites such as uridine diphosphate glucose (UDP-G) within the halo nevus. UDP-G, accompanied by the infiltration of DCs and T cells, exhibited correlations with certain forms of cell death. Subsequent experiments confirmed that UDP-G was increased in vitiligo serum and could activate DCs. We also confirmed that oxidative response is an inducer of UDP-G. In summary, the immune response in halo nevus, including DC activation, was accompanied by abnormal cell death and metabolites. Especially, melanocyte-derived UDP-G may play a crucial role in DC activation.
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Células Dendríticas , Melanócitos , Nevo com Halo , Humanos , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Melanócitos/metabolismo , Melanócitos/imunologia , Nevo com Halo/metabolismo , Nevo com Halo/imunologia , Uridina Difosfato Glucose/metabolismo , Vitiligo/imunologia , Vitiligo/metabolismo , Masculino , Feminino , Adulto , Apoptose , Linfócitos T/imunologia , Linfócitos T/metabolismo , Adulto Jovem , AdolescenteRESUMO
BACKGROUND: Little evidence exists about whether a combination of healthy lifestyle factors is associated with a lower risk of depressive symptoms among Chinese population. We aimed to investigate the association between combined healthy lifestyle factors and risk of depressive symptoms. METHODS: We conducted a baseline survey from July 2021 to December 2023, including 53,642 Chinese adults from general population. A healthy lifestyle score was constructed based on six lifestyle factors (physical activity, smoking status, alcohol consumption, diet, sleep duration, and body mass index). Logistic regression models were used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) adjusted for confounding variables. RESULTS: Each additional healthy lifestyle score was associated with a 20 % lower risk of having depressive symptoms (OR (95 % CI): 0.80 (0.78-0.81)). Compared with individuals with ≤2 healthy lifestyle factors, individuals with all the six healthy lifestyle factors had a 58 % reduced risk of having depressive symptoms (0.42 (0.37-0.47)). After stratification by gender, education and urbanization, the significant inverse association with healthy lifestyle score was stronger in women, individuals with high education, and urban residents. Besides, the significant negative association between healthy lifestyle score and depressive symptoms remained for different severity of depressive symptoms. LIMITATIONS: Given the cross-sectional nature of data, we cannot make causal inferences. CONCLUSIONS: Our study indicated that adherence to healthy lifestyle factors was associated with a reduced risk of having depressive symptoms among Chinese adults. The observed associations were modified by gender, education and urbanization. These findings warrant further verification in interventional studies.
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Chronic obstructive pulmonary disease (COPD) is characterised by persistent airway inflammation even after cigarette smoking cessation. Neutrophil extracellular traps (NETs) have been implicated in COPD severity and acute airway inflammation induced by short-term cigarette smoke (CS). However, whether and how NETs contribute to sustained airway inflammation in COPD remain unclear. This study aimed to elucidate the immunoregulatory mechanism of NETs in COPD, employing human neutrophils, airway epithelial cells (AECs), dendritic cells (DCs), and a long-term CS-induced COPD mouse model, alongside cyclic guanosine monophosphate-adenosine monophosphate synthase and toll-like receptor 9 knockout mice (cGAS--/-, TLR9-/-); Additionally, bronchoalveolar lavage fluid (BALF) of COPD patients was examined. Neutrophils from COPD patients released greater cigarette smoke extract (CSE)-induced NETs (CSE-NETs) due to mitochondrial respiratory chain dysfunction. These CSE-NETs, containing oxidatively-damaged DNA (NETs-DNA), promoted AECs proliferation, nuclear factor kappa B (NF-κB) activation, NF-κB-dependent cytokines and type-I interferons production, and DC maturation, which were ameliorated/reversed by silencing/inhibition of cGAS/TLR9. In the COPD mouse model, blocking NETs-DNA-sensing via cGAS-/- and TLR9-/- mice, inhibiting NETosis using mitoTEMPO, and degrading NETs-DNA with DNase-I, respectively, reduced NETs infiltrations, airway inflammation, NF-κB activation and NF-κB-dependent cytokines, but not type-I interferons due to IFN-α/ß receptor degradation. Elevated NETs components (myeloperoxidase and neutrophil elastase activity) in BALF of COPD smokers correlated with disease severity and NF-κB-dependent cytokine levels, but not type-I interferon levels. In conclusion, NETs-DNA promotes NF-κB-dependent autoimmunity via cGAS/TLR9 in long-term CS exposure-induced COPD. Therefore, targeting NETs-DNA and cGAS/TLR9 emerges as a potential strategy to alleviate persistent airway inflammation in COPD.
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Armadilhas Extracelulares , NF-kappa B , Neutrófilos , Nucleotidiltransferases , Doença Pulmonar Obstrutiva Crônica , Receptor Toll-Like 9 , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/patologia , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/imunologia , Armadilhas Extracelulares/imunologia , Armadilhas Extracelulares/genética , Nucleotidiltransferases/genética , Nucleotidiltransferases/imunologia , Animais , Humanos , NF-kappa B/genética , NF-kappa B/imunologia , NF-kappa B/metabolismo , Camundongos , Neutrófilos/imunologia , Neutrófilos/patologia , Camundongos Knockout , Autoimunidade/genética , Masculino , DNA/genética , DNA/imunologia , Feminino , Modelos Animais de Doenças , Pessoa de Meia-IdadeRESUMO
Colorectal cancer (CRC) is one of the most common gastrointestinal cancers that results in death in worldwide. The Hedgehog (HH) signalling pathway regulates the initiation and progression of CRC. Inhibiting the HH pathway has been presented as a potential treatment strategy in recent years. Cynanbungeigenin C (CBC) is a new type of C21 steroid that has been previously reported for the treatment of medulloblastoma. However, its further investigation was limited by its poor water solubility. In this study, six new CBC derivatives were synthesized through the structural modification of CBC, and four of them showed better water solubility than CBC. Moreover, their antiproliferative activities on CRC were evaluated. It was found that CBC-1 presented the best inhibitory effect on three types of CRC cell lines, and this effect was superior to that of CBC. Mechanistically, CBC-1 inhibited the proliferation of CRC cells through regulation of mRNA and proteins of the HH pathway according to qRT-PCR and Western blotting analysis. Furthermore, Cellular Thermal Shift Assay results indicated that CBC-1 regulated this signalling pathway by targeting gliomaassociated oncogene (GLI 1).In addition, cell apoptosis was induced increasingly by transfection with GLI 1 siRNA or treatment with CBC-1 to downregulate GLI 1. Last, the in vivo results demonstrated that CBC-1 significantly reduced tumour size and downregulated GLI 1 in CRC. Therefore, this study suggests that CBC-1, a new GLI 1 inhibitor derived from natural products, may be developed as a potential antitumour candidate for CRC treatment.
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Antineoplásicos , Apoptose , Proliferação de Células , Neoplasias Colorretais , Proteínas Hedgehog , Transdução de Sinais , Proteína GLI1 em Dedos de Zinco , Humanos , Proteína GLI1 em Dedos de Zinco/metabolismo , Proteína GLI1 em Dedos de Zinco/antagonistas & inibidores , Proteína GLI1 em Dedos de Zinco/genética , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Camundongos , Linhagem Celular Tumoral , Camundongos Nus , Relação Estrutura-Atividade , Ensaios de Seleção de Medicamentos Antitumorais , Camundongos Endogâmicos BALB CRESUMO
Active matter systems, which convert internal chemical energy or energy from the environment into directed motion, are ubiquitous in nature and exhibit a range of emerging non-equilibrium behaviors. However, most of the current works on active matter have been devoted to particles, and the study of active polymers has only recently come into the spotlight due to their prevalence within living organisms. The intricate interplay between activity and conformational degrees of freedom gives rise to novel structural and dynamical behaviors of active polymers. Research in active polymers remarkably broadens diverse concepts of polymer physics, such as molecular architecture, dynamics, scaling and so on, which is of significant importance for the development of new polymer materials with unique performance. Furthermore, active polymers are often found in strongly interacting and crowded systems and in complex environments, so that the understanding of this behavior is essential for future developments of novel polymer-based biomaterials. This review thereby focuses on the study of active polymers in complex and crowded environments, and aims to provide insights into the fundamental physics underlying the adaptive and collective behaviors far from equilibrium, as well as the open challenges that the field is currently facing.
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Immune functional decline and remodeling accompany aging and frailty. It is still largely unknown how changes in the immune cellular composition differentiate healthy individuals from those become frail at a relatively early age. Our aim in this exploratory study was to investigate immunological changes from newborn to frailty, and the association between health statute and various immune cell subtypes. The participants analyzed in this study covered human cord blood cells and peripheral blood cells collected from young adults, healthy and frail old individuals. A total of 30 immune cell subsets was performed by flow cytometry based on the surface markers of immune cells. Furthermore, frailty was investigated for its relations with various leukocyte subpopulations. Frail individuals exhibited a higher CD4/CD8 ratio, a higher proportion of CD4+ central memory T (TCM) cells, CD8+ effector memory T cells, CD27- switched memory B (CD27-BSM) cells, CD27+ switched memory B cells, age-associated B cells (ABCs) and CD38-CD24- B cells, and a lower proportion of naïve CD8 + T cells and progenitor B cells. The Frailty index score was found to be associated with naïve T cells, CD4/CD8 ratio, ABCs, CD27-BSM cells, and CD4+ TCM cells. Our findings conducted a relatively comprehensive and extensive atlas of age- and frailty-related changes in peripheral leukocyte subpopulations from newborn to frailty. The immune phenotypes identified in this study can contribute to a deeper understanding of immunosenescence in frailty and may provide a rationale for future interventions and diagnosis.
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Crystallization on spherical surfaces is obliged by topology to induce lattice defects. But controlling the organization of such defects remains a great challenge due to the long-range constraints of the curved geometry. Here, we report on DNA-coated colloids whose programmable interaction potentials can be used to regulate the arrangement of defects and even achieve perfect icosahedral order on a sphere. Combined simulations and theoretical analysis show how the potential can be tuned by changing the temperature, thereby controlling the number of defects. An explicit expression for the effective potential is derived, allowing us to distinguish the effects of entropic repulsion and enthalpic attraction. Altogether, the present findings provide insights into the physics of crystallization on curved spaces and may be used for designing desired crystal geometries.
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Branches covering (BC) is a way to reuse the pruned branches and save the cost of ground cloth. This study investigated the effects of BC and ground-cloth covering on the soil microcosm environment by measuring the chemical properties and microbial communities at different soil depths for 6 years. The results revealed that BC significantly improved soil chemical properties, increased the abundance of bacterial microbial communities and the diversity and homogeneity of bacteria and fungi, while decreased the abundance of fungal microbial communities. There was a threshold value for the regulation of microbial communities by BC, which decreased the high-abundance communities (Proteobacteria, Ascomycota, etc.) and increased the low-abundance communities (Acidobacteriota, Basidiomycota, etc.). Fungi were more sensitive to BC than bacteria. The stability and homogeneity of microorganisms were stronger in the 15-25 cm soil layer. The bacterial phyla were dominated by Proteobacteria, with the top 10 phyla accounting for more than 80% of the relative abundance; the genera were dominated by MND1, with the top 10 genera accounting for about 10%. The fungal phyla were dominated by Ascomycota, with the top 10 phyla accounting for 50-90%; the genera were dominated by unidentified Pyronemataceae sp., with the top 10 genera accounting for 30-60%. The phyla that differed significantly between treatments were mainly Proteobacteria, Ascomycota, Acidobacteriota, and Basidiomycota. In addition, metabolism was the predominant function in bacteria, while Saprotroph was the predominant function in fungi. Bacteroidota correlated strongly with soil chemical properties and bacterial functions, while Chytridiomycota correlated strongly with soil chemical properties and Pathogen-Saprotroph-Symbiotroph. In conclusion, BC can improve soil nutrient content and optimize microbial community structure and function. Through initially assessing the effects of BC on soil nutrients and microorganisms in pear orchard rows, this study provides a reference for excavating key microorganisms and updating the soil row management model.
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Transport of rodlike particles in confinement environments of macromolecular networks plays crucial roles in many important biological processes and technological applications. The relevant understanding has been limited to thin rods with diameter much smaller than network mesh size, although the opposite case, of which the dynamical behaviors and underlying physical mechanisms remain unclear, is ubiquitous. Here, we solve this issue by combining experiments, simulations and theory. We find a nonmonotonic dependence of translational diffusion on rod length, characterized by length commensuration-governed unconventionally fast dynamics which is in striking contrast to the monotonic dependence for thin rods. Our results clarify that such a fast diffusion of thick rods with length of integral multiple of mesh size follows sliding dynamics and demonstrate it to be anomalous yet Brownian. Moreover, good agreement between theoretical analysis and simulations corroborates that the sliding dynamics is an intermediate regime between hopping and Brownian dynamics, and provides a mechanistic interpretation based on the rod-length dependent entropic free energy barrier. The findings yield a principle, that is, length commensuration, for optimal design of rodlike particles with highly efficient transport in confined environments of macromolecular networks, and might enrich the physics of the diffusion dynamics in heterogeneous media.
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In order to understand the distribution of microorganisms and various antibiotic resistance genes in the aquaculture area of Changli County, Qinhuangdao, high-throughput sequencing technology was used in this study. We utilized 16S rDNA gene sequencing and metagenome sequencing methods to analyze the seawater, sediment, and gut contents of the local fish Synechogobius hasta in the aquaculture area in spring. The results showed that Proteobacteria, Firmicutes, and Bacteroidota were the dominant bacteria in seawater; and Proteobacteria, Crenarchaeota, Acidobacter, and Actinobaciota were rich in the sediment; whereas Proteobacteria, Cyanobacteria, Firmicutes, and Bacteroidota were in relatively high abundance in fish gut contents. The microbial diversity of sediment samples was the most abundant, followed by seawater samples, and the microbial diversity of fish intestinal contents was the lowest. Moreover, the microbial diversity of similar samples was relatively similar, and the microbial diversity of different types of samples was quite different. For samples at different sites, there were significant differences between seawater samples at each site, and there were small differences between sediment samples at each site, and some sediment sample groups did not have significant differences in microbial composition. In all sample groups, five ß-lactam antibiotic resistance genes (blaOXA-325, cepS, blaCARB-20, blaOXA-55, and blaTRU-1) and four aminoglycoside antibiotic resistance genes[aac(6')-IIb, amrA, aac(6')-Ie-aph(2â³)-Ia, and aph(3')-Vc] were detected. There was also a certain correlation between antibiotic resistance genes and microbial communities.
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Antibacterianos , Bactérias , Animais , Antibacterianos/análise , Bactérias/genética , Genes Bacterianos , Aquicultura , Resistência Microbiana a Medicamentos/genética , Peixes/genética , RNA Ribossômico 16SRESUMO
To overcome the limitations of traditional platinum (Pt)-based drugs and further improve the targeting ability and therapeutic efficacy in vivo, we proposed to design a human serum albumin (HSA)-Pt agent complex nanoparticle (NP) for cancer treatment by multimodal action against the tumor microenvironment. We not only synthesized a series of Pt(II) di-2-pyridone thiosemicarbazone compounds and obtained a Pt(II) agent [Pt(Dp44mT)Cl] with significant anticancer activity but also successfully constructed a novel HSA-Pt(Dp44mT) complex nanoparticle delivery system. The structure of the HSA-Pt(Dp44mT) complex revealed that Pt(Dp44mT)Cl binds to the IIA subdomain of HSA and coordinates with His-242. The HSA-His242-Pt-Dp44mT NPs had an obvious effect on the inhibition of tumor growth, which was superior to that of Dp44mT and Pt(Dp44mT)Cl, and they had almost no toxicity. In addition, the HSA-His242-Pt-Dp44mT NPs were found to kill cancer cells by inducing apoptosis, autophagy, and inhibiting angiogenesis.
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Antineoplásicos , Nanopartículas , Neoplasias , Humanos , Albumina Sérica Humana/química , Platina , Microambiente Tumoral , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Antineoplásicos/química , Linhagem Celular TumoralRESUMO
Introduction: Brain development during infancy is crucial for later health and development. Although Milk Fat Globule Membrane (MFGM) has been demonstrated to enhance brain development, further investigation is needed to determine the optimal dose. Methods: In this study, 80 piglets aged 2 days were randomly assigned to four groups: Control group, MFGM-L (1.74 g MFGM per 100 g diet), MFGM-M (4.64 g MFGM per 100 g diet), and MFGM-H (6.09 g MFGM per 100 g diet). Daily body weight and milk intake of the piglets were recorded until 31 days postnatal. Learning and memory abilities were evaluated using the spatial T-maze test on day 15. MRI analysis was conducted to assess functional and structural changes in brain tissues. Additionally, mRNA and protein expression of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NTF-3) in the hippocampus and prefrontal cortex were evaluated. Results: The results indicated that the MFGM supplemented diet significantly improved the accuracy of the piglets in the T-maze test, with the MFGM-L group exhibiting the best performance. MRI showed no volumetric differences in the gray and white matter between the groups. However, the fractional anisotropy in the left and right hippocampus of piglets in the MFGM-L group was significantly higher than in the other three groups. Furthermore, there was a strong correlation between the accuracy of the T-maze test and hippocampal fractional anisotropy. Discussion: The MFGM supplemented diet also increased the expression of BDNF in the cerebral cortex. However, the changes in BDNF were not consistent with the results of the T-maze test. In conclusion, adding 1.74 g MFGM per 100 g diet can significantly improve neonatal piglets' learning and memory abilities, potentially by enhancing the connection of white matter fiber bundles in the brain.
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The objective of this study is to explore the application effect of B-ultrasound positioning in assisting nasointestinal tube implantation in critically ill patients. This study is a retrospective study. In this study, 90 cases of severe patients with nasointestinal tube implantation were included. According to the different ways of nasointestinal tube insertion received by patients, 61 patients with conventional blind insertion methods were included in the blind insertion group, and 29 patients with conventional methods and B-ultrasound assisted positioning were included in the B-ultrasound positioning group. The general clinical data, success rate of catheterization, catheterization time, pyloric passage rate, and target nutritional value time of the 2 groups were compared. The changes of the 2 groups after catheterization were compared by SOFA and APACHE II. The contents of albumin and lymphocyte count were compared between the 2 groups before and after catheterization. The time of target nutritional value of the patients of the B-ultrasound positioning group was markedly decreased comparing with the patients of the blind insertion group. The index of catheterization time of the patients between the blind insertion group and B-ultrasound positioning group had no obvious contrast. The APACHE II score and SOFA score of the patients of the B-ultrasound positioning group were obviously lower than the blind insertion group. The contents of lymphocyte count of the patients of the B-ultrasound positioning group were markedly increased comparing with the patients of the blind insertion group after catheterization, but the contents of albumin content had no obvious change. The scores of respiratory system, circulatory system, nervous system, and urinary system in the B-ultrasound positioning group were significantly higher than those in the blind insertion group, while the COPT scores were significantly lower than those in the blind insertion group. B-ultrasound assisted nasointestinal tube implantation is well tolerated in critically ill patients, and can effectively ameliorate the nutritional status and of the ill patients.
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Estado Terminal , Intubação Gastrointestinal , Humanos , Estado Terminal/terapia , Estudos Retrospectivos , Intubação Gastrointestinal/métodos , Nutrição Enteral , AlbuminasRESUMO
BACKGROUND: Pleural effusion (PE) is reported as a common complication in acute pancreatitis (AP), while the incidence of PE in AP varies widely among studies, and the association between PE and mortality is not clear. This study aimed to comprehensively analyze the pooled incidence of PE in patients with AP and to evaluate the influence of PE on mortality through a meta-analysis. METHOD: Six databases (PubMed, Web of Science, EMBASE, Cochrane, Scopus, and OVID) were searched thoroughly for relevant studies. Data were extracted, and Stata SE 16.0 software was applied to compute the pooled incidence of PE and assess the association between PE and mortality, taking the risk ratio (RR) as the effect size. RESULTS: Thirty-five articles involving 7,675 patients with AP were eventually included in this meta-analysis. The pooled incidence of PE was 34% (95% CI: 28%-39%), with significant heterogeneity among studies (I2=96.7%). Further analysis revealed that the pooled incidence of unilateral and small PE occupied 49% (95% CI: 21%-77%) and 59% (95% CI: 38%-81%) of AP patients complicated by PE, respectively. The subgroup analysis revealed that "region" and "examination method" may contribute to heterogeneity. PE may be associated with increased mortality in AP patients (RR 3.99, 95% CI: 1.73-9.2). CONCLUSION: This study suggested that PE is a common complication with high pooled incidence and that PE may be associated with increased mortality in AP patients. More studies should be performed to validate our findings.
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Pancreatite , Derrame Pleural , Humanos , Pancreatite/complicações , Pancreatite/epidemiologia , Prognóstico , Doença Aguda , Incidência , Derrame Pleural/epidemiologia , Derrame Pleural/etiologiaRESUMO
Alkene dicarbofunctionalization is an efficient strategy and operation-economic fashion for introducing complexity in molecules. A nickel/photoredox dual catalyzed arylalkylation of nonactivated alkenes for the simultaneous construction of one C(sp3)-C(sp3) bond and one C(sp3)-C(sp2) bond has been developed. The mild catalytic method provided valuable indanethylamine derivatives with wide substrate scope and good functional group compatibility. An enantioselective dicarbofunctionalization was also achieved with pyridine-oxazoline as a ligand. The efficiency of metallaphotoredox dicarbofunctionalization was demonstrated for the concise synthesis of pharmaceutically active compounds.
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BACKGROUND: Blood-based tests have public appeal in screening cancers due to their minimally invasive nature, ability to integrate with other routine blood tests, and high compliance. This study aimed to investigate whether certain epigenetic modulation of peripheral blood mononuclear cells (PBMCs) could be a biomarker of colorectal cancer (CRC). RESULTS: Western blotting of histones in the PBMCs from 40 colorectal cancer patients and 40 healthy controls was performed to identify the crotonylation sites of proteins. The correlation of crotonylation with tumor staging and diagnostic efficacy were analyzed. Crotonylation of H2BK12 (H2BK12cr) was identified significantly upregulated in the PBMCs of CRC patients compared to healthy controls, and were closely related to distant metastasis (P = 0.0478) and late TNM stage (P = 0.0201). Receiver operator characteristic curve (ROC) analysis demonstrated that the area under curve (AUC) of H2BK12cr was 0.8488, the sensitivity was 70%, and the specificity was 92.5%. The H2BK12cr parameter significantly increased the diagnostic effectiveness of CRC compared with the commercial carcinoembryonic antigen assays. CONCLUSIONS: The H2BK12cr level in PBMCs of CRC patients has a potential to be a biomarker for distinguishing CRC patients from healthy controls with the advantages of easy operation and high diagnostic efficacy.
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Neoplasias Colorretais , Histonas , Humanos , Leucócitos Mononucleares , Biomarcadores , Epigenômica , Neoplasias Colorretais/diagnósticoRESUMO
Self-assembly of various building blocks has been considered as a powerful approach to generate novel materials with tailorable structures and optimal properties. Understanding physicochemical interactions and mechanisms related to structural formation and transitions is of essential importance for this approach. Although it is well-known that diverse forces and energies can significantly contribute to the structures and properties of self-assembling systems, the potential entropic contribution remains less well understood. The past few years have witnessed rapid progress in addressing the entropic effects on the structures, responses, and functions in the self-assembling systems, and many breakthroughs have been achieved. This review provides a framework regarding the entropy-controlled strategy of self-assembly, through which the structures and properties can be tailored by effectively tuning the entropic contribution and its interplay with the enthalpic counterpart. First, we focus on the fundamentals of entropy in thermodynamics and the entropy types that can be explored for self-assembly. Second, we discuss the rules of entropy in regulating the structural organization in self-assembly and delineate the entropic force and superentropic effect. Third, we introduce the basic principles, significance and approaches of the entropy-controlled strategy in self-assembly. Finally, we present the applications where this strategy has been employed in fields like colloids, macromolecular systems and nonequilibrium assembly. This review concludes with a discussion on future directions and future research opportunities for developing and applying the entropy-controlled strategy in complex self-assembling systems.
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Colorectal cancer (CRC) is one of the malignant tumors with the highest morbidity and mortality and poor prognosis. The mammalian gene family of Cab45/reticulocalbin/ERC-45/calumenin (CREC) consists of RCN1, RCN2, RCN3, SDF4 and CALU. Although CREC family members have been associated with CRC, the expression pattern, prognostic value, and the role of CREC family in CRC remain unclear. In this study, the expression, survival and biological functions of CREC family in CRC were determined via bioinformatic datasets analysis and experimental verification on clinical CRC specimen. Bioinformatic analysis showed that the expression levels of most CREC family genes were higher in CRC tissues than in normal colorectal tissues. The qPCR and western blot results also revealed that the transcriptional and protein levels of CREC family were elevated in CRC tissues compared with adjacent tissues. Besides, CREC family was significantly correlated with advanced tumor stage and poor prognosis of CRC patients. The expression levels of CREC family had correlations with genomic mutation and methylation, and with the infiltration levels of CD4 + T cells, macrophages, neutrophils, and dendritic cells in the microenvironment of CRC. Functional networks enrichment analysis indicated that the genes of CREC family were essential factors for CRC metastasis. Collectively, these findings suggest that CREC family might be potential targets for the treatment of CRC and candidate prognostic markers for CRC patients.
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Linfócitos T CD4-Positivos , Neoplasias Colorretais , Animais , Humanos , Prognóstico , Western Blotting , Biologia Computacional , Neoplasias Colorretais/genética , Mamíferos , Microambiente Tumoral , Proteínas de Ligação ao CálcioRESUMO
Recurrence is a significant adverse outcome of ischemic stroke (IS), particularly in cases of intracranial arteriosclerosis (ICAS). In this study, we investigated the impact of imaging features of culprit plaque using high-resolution magnetic resonance vessel wall imaging (HR-MR-VWI) on the prediction of IS recurrence. A total of 86 patients diagnosed with ICAS-related IS within the middle cerebral artery (MCA) territory were included, of which 23.25% experienced recurrent IS within one year. Our findings revealed significant differences between the recurrence and non-recurrence groups in terms of age (p = 0.007), diabetes mellitus (p = 0.031), hyperhomocysteinemia (p = 0.021), artery-artery embolism (AAE) infarction (p = 0.019), prominent enhancement (p = 0.013), and surface irregularity of the culprit plaque (p = 0.009). Age (HR = 1.063, p = 0.005), AAE infarction (HR = 5.708, p = 0.008), and prominent enhancement of the culprit plaque (HR = 4.105, p = 0.025) were identified as independent risk factors for stroke recurrence. The areas under the receiver operating characteristic curve (AUCs) for predicting IS recurrence using clinical factors, conventional imaging findings, HR-MR-VWI plaque features, and a combination of clinical and conventional imaging models were 0.728, 0.645, 0.705, and 0.814, respectively. Notably, the combination model demonstrated superior predictive performance with an AUC of 0.870. Similarly, AUC of combination model for predicting IS recurrence in validation cohort which enrolled another 37 patients was 0.865. In conclusion, the presence of obvious enhancement in culprit plaque on HR-MR-VWI is a valuable factor in predicting IS recurrence in ICAS-related strokes within the MCA territory. Furthermore, our combination model, incorporating plaque features, exhibited improved prediction accuracy.