Interaction of human mesenchymal stem cells with soft nanocomposite hydrogels based on polyethylene glycol and dendritic polyglycerol

Keeping the stemness of human mesenchymal stem cells (hMSCs) and their adipocyte differentiation potential is critical for clinical use. However, these features are lost on traditional substrates. hMSCs have often been studied on stiff materials whereas culturing hMSCs in their native niche increases their potential. Herein, a patterned hydrogel nanocomposite with the stiffness of liver tissues is obtained without any molding process. To investigate hMSCs' mechanoresponse to the material, the RGD spacing units and the stiffness of the hydrogels are dually tuned via the linker length. This work suggests that hMSCs' locomotion is influenced by the nature of the hydrogel layer (bulk or thin film). Contrary to on bulk surfaces, cell traction occurs during cell spreading on thin films. In addition, hMSCs' spreading behavior varies from shorter to longer linker‐based hydrogels, where on both surfaces hMSCs maintains their stemness as well as their adipogenic differentiation potential with a higher number of adipocytes for nanocomposites with a longer polymer linker. Overall, this work addresses the need for a new alternative for hMSCs culture allowing the cells to differentiate exclusively into adipocytes. This material represents a cell‐responsive platform with a tissue‐mimicking architecture given by the mechanical and morphological properties of the hydrogel

Near-Field Integrated Sensing, Positioning, and Communication: A Downlink and Uplink Framework

A near-field integrated sensing, positioning, and communication (ISPAC) framework is proposed, where a base station (BS) simultaneously serves multiple communication users and carries out target sensing and positioning. A novel double-array structure is proposed to enable the near-field ISPAC at the BS. Specifically, a small-scale assisting transceiver (AT) is attached to the large-scale main transceiver (MT) to empower the communication system with the ability of sensing and positioning. Based on the proposed framework, the joint angle and distance Cram\'er-Rao bound (CRB) is first derived. Then, the CRB is minimized subject to the minimum communication rate requirement in both downlink and uplink ISPAC scenarios: 1) For downlink ISPAC, a downlink target positioning algorithm is proposed and a penalty dual decomposition (PDD)-based double-loop algorithm is developed to tackle the non-convex optimization problem. 2) For uplink ISPAC, an uplink target positioning algorithm is proposed and an efficient alternating optimization algorithm is conceived to solve the non-convex CRB minimization problem with coupled user communication and target probing design. Both proposed optimization algorithms can converge to a stationary point of the CRB minimization problem. Numerical results show that: 1) The proposed ISPAC system can locate the target in both angle and distance domains merely relying on single BS and limited bandwidths; and 2) the positioning performance achieved by the hybrid-analog-and-digital ISPAC approaches that achieved by fully digital ISPAC when the communication rate requirement is not stringent.Comment: 13 pages, 6 figure

Fracture Analysis of Brittle Materials Based on Nonlinear FEM and Application in Arch Dam with Fractures

Current fracture analysis models based on fracture mechanics or continuum damage mechanics are still limited in the application to three-dimensional structure. Based on deformation reinforcement theory coming from elastoperfect plastic theory, unbalanced force is proposed to predict initiation and propagation of cracks. Unbalanced force is the driving force of time-dependent deformation according to Perzyna’s viscoplasticity theory. It is also related to the damage driving force in viscoplastic damage model. The distribution of unbalanced force indicates cracks initiation area, while its direction predicts possible cracks propagation path. Uniaxial compression test of precrack specimen is performed as verification to this method. The trend and distribution of cracks are in good agreement with numerical results, proving that unbalanced force is feasible and effective for fracture analysis. The method is applied in fracture analysis of Xiaowan high arch dam, which is subjected to some cracks in dam due to the temperature control program. The results show that the deformation and stress of cracks and the stress characteristics of dam are insensitive to grouting of cracks. The existing cracks are stable and dam heel is still the most possible cracking position

Dendritic Polyglycerol-Conjugated Gold Nanostars for Metabolism Inhibition and Targeted Photothermal Therapy in Breast Cancer Stem Cells

Breast cancer stem cells (CSCs) are believed to be responsible for tumor initiation, invasion, metastasis, and recurrence, which lead to treatment failure. Thus, developing effective CSC-targeted therapeutic strategies is crucial for enhancing therapeutic efficacy. In this work, GNSs-dPG-3BP, TPP, and HA nanocomposite particles are developed by simultaneously conjugating hexokinase 2 (HK2) inhibitor 3-bromopyruvate (3BP), mitochondrial targeting molecule triphenyl phosphonium (TPP), and CSCs targeting agent hyaluronic acid (HA) onto gold nanostars-dendritic polyglycerol (GNSs-dPG) nanoplatforms for efficient eradication of CSCs. The nanocomposite particles possess good biocompatibility and exhibit superior mitochondrial-bound HK2 binding ability via 3BP to inhibit metabolism, and further induce cellular apoptosis by releasing the cytochrome c. Therefore, it enhanced the therapeutic efficacy of CSCs-specific targeted photothermal therapy (PTT), and achieved a synergistic effect for the eradication of breast CSCs. After administration of the synergistic treatment, the self-renewal of breast CSCs and the stemness gene expression are suppressed, CSC-driven mammosphere formation is diminished, the in vivo tumor growth is effectively inhibited, and CSCs are eradicated. Altogether, GNSs-dPG-3BP, TPP, and HA nanocomposite particles have been developed, which will provide a novel strategy for precise and highly efficient targeted eradication of CSCs

Eightfold Fermionic Excitation in a Charge Density Wave Compound

Unconventional quasiparticle excitations in condensed matter systems have become one of the most important research frontiers. Beyond two- and fourfold degenerate Weyl and Dirac fermions, three-, six- and eightfold symmetry protected degeneracies have been predicted however remain challenging to realize in solid state materials. Here, charge density wave compound TaTe4 is proposed to hold eightfold fermionic excitation and Dirac point in energy bands. High quality TaTe4 single crystals are prepared, where the charge density wave is revealed by directly imaging the atomic structure and a pseudogap of about 45 meV on the surface. Shubnikov de-Haas oscillations of TaTe4 are consistent with band structure calculation. Scanning tunneling microscopy reveals atomic step edge states on the surface of TaTe4. This work uncovers that charge density wave is able to induce new topological phases and sheds new light on the novel excitations in condensed matter materials.Comment: Accepted by PRB: https://journals.aps.org/prb/accepted/7907cK4eW0b1ee0b93fd67c1b42942bbb08eafc3

Genome Assembly for a Yunnan-Guizhou Plateau “3E” Fish, Anabarilius grahami (Regan), and Its Evolutionary and Genetic Applications

A Yunnan-Guizhou Plateau fish, the Kanglang white minnow (Anabarilius grahami), is a typical “3E” (Endangered, Endemic, and Economic) species in China. Its distribution is limited to Fuxian Lake, the nation’s second deepest lake, with a significant local economic value but a drastically declining wild population. This species has been evaluated as VU (Vulnerable) in the China Species Red List. As one of the “Four Famous Fish” in Yunnan province, the artificial breeding has been achieved since 2003. It has not only re-established its wild natural populations by reintroduction of the artificial breeding stocks, but also brought a wide and popular utilization of this species to the local fish farms. A. grahami has become one of the main native aquaculture species in Yunnan province, and the artificial production has been emerging in steady growth each year. To promote the conservation and sustainable utilization of this fish, we initiated its whole genome sequencing project using an Illumina Hiseq2500 platform. The assembled genome size of A. grahami is 1.006 Gb, accounting for 98.63% of the estimated genome size (1.020 Gb), with contig N50 and scaffold N50 values of 26.4 kb and 4.41 Mb, respectively. Approximately about 50.38% of the genome was repetitive. A total of 25,520 protein-coding genes were subsequently predicted. A phylogenetic tree based on 4,580 single-copy genes from A. grahami and 18 other cyprinids revealed three well-supported subclades within the Cyprinidae. This is the first inter-subfamily relationship of cyprinids at genome level, providing a simple yet useful framework for understanding the traditional but popular subfamily classification systems. Interestingly, a further population demography of A. grahami uncovered a historical relationship between this fish and Fuxian Lake, suggesting that range expansion or shrinkage of the habitat has had a remarkable impact on the population size of endemic plateau fishes. Additionally, a total of 33,836 simple sequence repeats (SSR) markers were identified, and 11 loci were evaluated for a preliminary genetic diversity analysis in this study, thus providing another useful genetic resource for studying this “3E” species

Dual Antiplatelet Treatment up to 72 Hours after Ischemic Stroke

BackgroundDual antiplatelet treatment has been shown to reduce recurrence of stroke compared to aspirin alone when initiated early after an acute stroke. The effect of clopidogrel and aspirin versus aspirin alone within 72 hours of acute cerebral ischemia from atherosclerosis has not been well studied.MethodsWe conducted a randomized, double-blind, placebo-controlled, 2-by-2 factorial trial in patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) of presumed atherosclerotic cause, not receiving thrombolysis or thrombectomy in 222 hospitals in China. Patients were randomly assigned within 72 hours after symptom onset in a 1:1 ratio, to receive clopidogrel (300mg on day 1, 75mg daily on days 2-90) and aspirin (100-300mg on day1, 100mg daily on days 2-21), or clopidogrel placebo and aspirin (100-300mg on day1, 100mg daily on days 2-90). There was no interaction between this component of the factorial trial design trial and a second part that tested immediate vs delayed stain treatment and is reported separately. The primary efficacy outcome was a new stroke, and the primary safety outcome was moderate-to-severe bleeding, both within 90 days.ResultsA total of 6100 patients were enrolled, 3050 assigned to each trial group. The qualifying event for enrollment was TIA in 13%. Approximately 13% of patients were assigned to a treatment group within 24 hours and 87% were assigned between 24 and 72 hours of onset of stroke. A new stroke occurred in 222 (7.3%) in the clopidogrel-aspirin group, and 279 (9.2%) in the aspirin group (hazard ratio, 0.79; 95% confidence interval [CI], 0.66-0.94; P=0.008). Moderate-to-severe bleeding occurred in 27 (0.9%) and 13 patients (0.4%), respectively (hazard ratio, 2.08; 95% CI, 1.07-4.04, P=0.03).ConclusionsAmong patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, combined clopidogrel-aspirin initiated within 72 hours of onset was superior to aspirin alone in reducing the risk of new stroke at 90 days but was associated with a low but increased risk of moderate-to-severe bleeding