Although the biological functions of cell and tissue can be regulated by biochemical factors (e.g., growth factors, hormones), the biophysical effects of materials on the regulation of biological ...activity are receiving more attention. In this Review, we systematically summarize the recent progress on how biomaterials with controllable properties (e.g., compositional/degradable dynamics, mechanical properties, 2D topography, and 3D geometry) can regulate cell behaviors (e.g., cell adhesion, spreading, proliferation, cell alignment, and the differentiation or self-maintenance of stem cells) and tissue/organ functions. How the biophysical features of materials influence tissue/organ regeneration have been elucidated. Current challenges and a perspective on the development of novel materials that can modulate specific biological functions are discussed. The interdependent relationship between biomaterials and biology leads us to propose the concept of “materiobiology”, which is a scientific discipline that studies the biological effects of the properties of biomaterials on biological functions at cell, tissue, organ, and the whole organism levels. This Review highlights that it is more important to develop ECM-mimicking biomaterials having a self-regenerative capacity to stimulate tissue regeneration, instead of attempting to recreate the complexity of living tissues or tissue constructs ex vivo. The principles of materiobiology may benefit the development of novel biomaterials providing combinative bioactive cues to activate the migration of stem cells from endogenous reservoirs (i.e., cell niches), stimulate robust and scalable self-healing mechanisms, and unlock the body’s innate powers of regeneration.
Cellular homeostasis requires the proper nuclear-cytoplasmic partitioning of large molecules, which is often deregulated in cancer. XPO1 is an export receptor responsible for the nuclear-cytoplasmic ...transport of hundreds of proteins and multiple RNA species. XPO1 is frequently overexpressed and/or mutated in human cancers and functions as an oncogenic driver. Suppression of XPO1-mediated nuclear export, therefore, presents a unique therapeutic strategy. In this review, we summarize the physiological functions of XPO1 as well as the development of various XPO1 inhibitors and provide an update on the recent clinical trials of the SINE compounds. We also discuss potential future research directions on the molecular function of XPO1 and the clinical application of XPO1 inhibitors.
Ultrasonic vibrations in coal lead to cavitation bubble oscillation, growth, shrinkage, and collapse, and the strong vibration of cavitation bubbles not only makes coal pores break and cracks ...propagate, but plays an important role in enhancing the permeability of coal. In this paper, the influence of ultrasonic cavitation on coal and the effects of the sonic waves on crack generation, propagation, connection, as well as the effect of cracks on the coal permeability, are studied. The experimental results show that cracks in coal are generated even connected rapidly after ultrasonic cavitation. Under the effect of ultrasonic cavitation,the permeability increases between 30% and 60%, and the number of cracks in coal also significantly increased. Numerical experiments show that the effective sound pressure is beneficial to fracture propagation and connection, and it is closely related to the permeability. Moreover, the numerical simulations and physical experiments provide a guide for the coal permeability improvement.
Quasicrystals are a class of materials with long-range order but no translational periodicity. Though many quasicrystals have been discovered, rational design and engineering of quasicrystals remain ...a great challenge. Herein, we have developed a rational strategy to assemble two-dimensional (2D), dodecagonal quasicrystals from branched DNA nanomotifs. The key of our strategy is to balance the rigidity and flexibility of the motifs, which is controlled by the introduction of interbranch “bridges”. By fine-tuning the experimental conditions, we are able to predictably produce either 2D quasicrystals or conventional crystals. This study presents a rational design, prediction and realization of quasicrystal formation.
Observational studies of the relationship between hyperuricemia and the incidence of hypertension are controversial. We conducted a systematic review and meta-analysis to assess the association and ...consistency between uric acid levels and the risk of hypertension development.
We searched MEDLINE, EMBASE, CBM (Chinese Biomedicine Database) through September 2013 and reference lists of retrieved studies to identify cohort studies and nested case-control studies with uric acid levels as exposure and incident hypertension as outcome variables. Two reviewers independently extracted data and assessed study quality using Newcastle-Ottawa Scale. Extracted information included study design, population, definition of hyperuricemia and hypertension, number of incident hypertension, effect sizes, and adjusted confounders. Pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) for the association between hyperuricemia and risk of hypertension were calculated using a random-effects model.
We included 25 studies with 97,824 participants assessing the association between uric acid and incident hypertension in our meta-analysis. The quality of included studies is moderate to high. Random-effects meta-analysis showed that hyperuricemia was associated with a higher risk of incident hypertension, regardless of whether the effect size was adjusted or not, whether the data were categorical or continuous as 1 SD/1 mg/dl increase in uric acid level (unadjusted: RR = 1.73, 95% CI 1.46∼2.06 for categorical data, RR = 1.22, 95% CI 1.03∼1.45 for a 1 SD increase; adjusted: RR = 1.48, 95% CI 1.33∼1.65 for categorical data, RR = 1.15, 95% CI 1.06∼1.26 for a 1 mg/dl increase), and the risk is consistent in subgroup analyses and have a dose-response relationship.
Hyperuricemia may modestly increase the risk of hypertension incidence, consistent with a dose-response relationship.
Graphene oxide (GO) can be reduced and decorated by bovine serum albumin (BSA) at suitable pH and temperature. The resulting bioconjugates between BSA and GO or reduced GO are ideal templates for ...highly efficient assembly of a variety of nanoparticles with dramatically different compositions, sizes, shapes, and properties. This methodology offers a great chance for investigations on the structure−performance relationship of hybrid nanomaterials toward combinatorial material design aiming at special functions and applications.
Myocardial ischemia-reperfusion (MI/R) injury is a significant clinical problem without effective therapy. Unbiased omics approaches may reveal key MI/R mediators to initiate MI/R injury.
We used a ...dynamic transcriptome analysis of mouse heart exposed to various MI/R periods to identify S100a8/a9 as an early mediator. Using loss/gain-of-function approaches to understand the role of S100a8/a9 in MI/R injury, we explored the mechanisms through transcriptome and functional experiment. Dynamic serum S100a8/a9 levels were measured in patients with acute myocardial infarction before and after percutaneous coronary intervention. Patients were prospectively followed for the occurrence of major adverse cardiovascular events.
S100a8/a9 was identified as the most significantly upregulated gene during the early reperfusion stage. Knockout of S100a9 markedly decreased cardiomyocyte death and improved heart function, whereas hematopoietic overexpression of S100a9 exacerbated MI/R injury. Transcriptome/functional studies revealed that S100a8/a9 caused mitochondrial respiratory dysfunction in cardiomyocytes. Mechanistically, S100a8/a9 downregulated NDUF gene expression with subsequent mitochondrial complex I inhibition via Toll-like receptor 4/Erk-mediated Pparg coactivator 1 alpha/nuclear respiratory factor 1 signaling suppression. Administration of S100a9 neutralizing antibody significantly reduced MI/R injury and improved cardiac function. Finally, we demonstrated that serum S100a8/a9 levels were significantly increased 1 day after percutaneous coronary intervention in patients with acute myocardial infarction, and elevated S100a8/a9 levels were associated with the incidence of major adverse cardiovascular events.
Our study identified S100a8/a9 as a master regulator causing cardiomyocyte death in the early stage of MI/R injury via the suppression of mitochondrial function. Targeting S100a8/a9-intiated signaling may represent a novel therapeutic intervention against MI/R injury.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT03752515.
The MYC oncogene codes for a transcription factor that is overexpressed in many human cancers. Here we show that MYC regulates the expression of two immune checkpoint proteins on the tumor cell ...surface: the innate immune regulator CD47 (cluster of differentiation 47) and the adaptive immune checkpoint PD-L1 (programmed death–ligand 1). Suppression of MYC in mouse tumors and human tumor cells caused a reduction in the levels of CD47 and PD-L1 messenger RNA and protein. MYC was found to bind directly to the promoters of the Cd47 and Pd-l1 genes. MYC inactivation in mouse tumors down-regulated CD47 and PD-L1 expression and enhanced the antitumor immune response. In contrast, when MYC was inactivated in tumors with enforced expression of CD47 or PD-L1, the immune response was suppressed, and tumors continued to grow. Thus, MYC appears to initiate and maintain tumorigenesis, in part, through the modulation of immune regulatory molecules.
Analogous to the atom–molecule relationship, nanoparticle (NP) clusters (or NP-molecules) with defined compositions and directional bonds could potentially integrate the properties of the component ...individual NPs, leading to emergent properties. Despite extensive efforts in this direction, no general approach is available for assembly of such NP-molecules. Here we report a general method for building this type of structures by encapsulating NPs into self-assembled DNA polyhedral wireframe nanocages, which serve as guiding agents for further assembly. As a demonstration, a series of NP-molecules have been assembled and validated. Such NP-molecules will, we believe, pave a way to explore new nanomaterials with emergent functions/properties that are related to, but do not belong to the individual component nanoparticles.