Ant-behavior inspired intelligent nanonet for targeted drug delivery in cancer therapy

Targeted drug delivery system is believed as one of the most promising solutions for cancer treatment due to its low-dose requirement and less side effects. However, both passive targeting and active targeting rely on systemic blood circulation and diffusion, which is actually not the real “active” drug delivery. In this paper, an ant-behavior inspired nanonetwork composing of intelligent nanomachines is proposed. A big intelligent nanomachine take small intelligent nanomachines and drugs to the vicinity of of the tumor area. The small intelligent nanomachines can coordinate with each other to find the most effective path to the tumor cell for drug transportation. The framework and mechanism of this cooperative network are proposed. The route finding algorithm is presented. The convergence performance is analytically analyzed where the influence of the factors such as molecule degradation rate, home-destination distance, number of small nanomachines to the convergence is presented. Finally the simulation results validate the effectiveness of the proposed mechanism and analytical analysi

A centi-pc-scale compact radio core in the nearby galaxy M60

M60, an elliptical galaxy located 16.5~Mpc away, has an active nucleus with a very low luminosity and an extremely low accretion rate. Its central supermassive black hole has a mass of $M_{\rm BH}\sim4.5\times10^{9}\, M_{\odot}$ and a Schwarzschild radii corresponding to $R_{\rm S}\sim5.4\,\mu\mathrm{as}$. To investigate the nature of its innermost radio nucleus, data from the Very Long Baseline Array (VLBA) at 4.4 and 7.6~GHz were reduced. The VLBA images reveal a compact component with total flux densities of $\sim$20~mJy at both frequencies, a size of $\leq$0.27~mas (99.7$\%$ confidence level), about 0.022~pc ($50\,R_{\rm S}$) at 7.6~GHz, and a brightness temperature of $\geq6\times10^{9}$~K. This suggests that the observed centi-parsec-scale compact core could be attributed to a nonthermal jet base or an advection-dominated accretion flow (ADAF) with nonthermal electrons. The extremely compact structure also supports the presence of an SMBH in the center. Our results indicate that M60 is a promising target for broad-band VLBI observations at millimeter wavelengths to probe ADAF scenarios and tightly constrain the potential photon ring (about 28\,$\mu$as) around its SMBH.Comment: 15 pages, 5 figures, 3 tables, accepted for publication in Astrophysical Journa

Preparation and hydration mechanism of aluminum formate/aluminum sulfate based alkali-free composite accelerator for sprayed concrete

The high alkali content of alkaline accelerators has a negative influence on the late strength and durability of concrete. Further, their corrosive nature is harmful to the skin of construction personnel, posing safety concerns. Therefore, the development of alkali-free accelerators has gained interest, especially in shotcrete-based constructions. The production process of aluminum-sulfate-based alkali-free accelerators is simple and less exothermic, with no negative impact on the later strength of concrete, aspects that are widely recognized and very important in construction. However, their high sulfate content may have a significant impact on the durability of concrete; therefore, reducing the sulfate content plays an important role in enhancing the durability of concrete. In this study, an alkali-free liquid accelerator was synthesized by replacing aluminum sulfate with aluminum formate, which effectively reduced the sulfate content. Experiments were performed on concrete samples in which aluminum sulfate was replaced with aluminum formate at different levels. The results showed that the formate and 3CaO·Al _2 O _3 (C _3 A) of the alkali-free liquid accelerator prepared from aluminum formate form calcium aluminate, similar to the ettringite phase. The formate promoted the dissolution of Ca _3 SiO _5 (C _3 S), thus accelerating the hydration of concrete. Meanwhile, aluminum ions hydrolyzed by aluminum formate also participated in the reaction, resulting in the dual participation of cations and anions in hydration, leading to a synergistic effect with aluminum sulfate

A robust iterative receiver for single carrier underwater acoustic communications under impulsive noise

Achieving reliable underwater acoustic (UWA) communications is challenging due to the rapid changes of UWA channels and presence of impulsive noise. The soft decision feedback equalization (SDFE) has attracted much attention due to its capability of tackling the rapid changes of UWA channels. However, the existing SDFE exhibits error floor and even divergence due to the presence of severe impulsive noise. To overcome this problem, an improved SDFE (ISDFE) is proposed, which incorporates impulsive noise detection, clipping level estimation and damping to handle the impulsive noise. As the performance of the ISDFE also depends on the accuracy of channel estimation (CE), we propose a variable kernel width maximum complex correntropy criterion Kalman filter (VKW-MCCC-KF) algorithm to achieve robust and accurate CE under impulsive noise. With the proposed ISDFE and VKW-MCCC-KF, an iterative receiver for single carrier (SC) UWA mobile communication under impulsive noise is proposed, which incorporates the adaptive broadband Doppler compensation, VKW-MCCC-KF based CE and ISDFE, working in an iterative manner. Experimental results show that, compared with existing receivers, the proposed receiver achieves better performance and robustness to impulsive noise under fast changing UWA channels

The m6A reader IGF2BP2 regulates glycolytic metabolism and mediates histone lactylation to enhance hepatic stellate cell activation and liver fibrosis

Abstract Evidence for the involvement of N6-Methyladenosine (m6A) modification in the etiology and progression of liver fibrosis has emerged and holds promise as a therapeutic target. Insulin-like growth factor 2 (IGF2) mRNA-binding protein 2 (IGF2BP2) is a newly identified m6A-binding protein that functions to enhance mRNA stability and translation. However, its role as an m6A-binding protein in liver fibrosis remains elusive. Here, we observed that IGF2BP2 is highly expressed in liver fibrosis and activated hepatic stellate cells (HSCs), and inhibition of IGF2BP2 protects against HSCs activation and liver fibrogenesis. Mechanistically, as an m6A-binding protein, IGF2BP2 regulates the expression of Aldolase A (ALDOA), a key target in the glycolytic metabolic pathway, which in turn regulates HSCs activation. Furthermore, we observed that active glycolytic metabolism in activated HSCs generates large amounts of lactate as a substrate for histone lactylation. Importantly, histone lactylation transforms the activation phenotype of HSCs. In conclusion, our findings reveal the essential role of IGF2BP2 in liver fibrosis by regulating glycolytic metabolism and highlight the potential of targeting IGF2BP2 as a therapeutic for liver fibrosis

A dual functional Ti-Ga alloy: inhibiting biofilm formation and osteoclastogenesis differentiation via disturbing iron metabolism

Abstract Background Although biomedical implants have been widely used in orthopedic treatments, two major clinical challenges remain to be solved, one is the bacterial infection resulting in biofilm formation, and the other is aseptic loosening during implantation due to over-activated osteoclastogenesis. These factors can cause many clinical issues and even lead to implant failure. Thus, it is necessary to endow implants with antibiofilm and aseptic loosening-prevention properties, to facilitate the integration between implants and bone tissues for successful implantation. To achieve this goal, this study aimed to develop a biocompatible titanium alloy with antibiofilm and anti-aseptic loosening dual function by utilizing gallium (Ga) as a component. Methods A series of Ti-Ga alloys were prepared. We examined the Ga content, Ga distribution, hardness, tensile strength, biocompatibility, and anti-biofilm performance in vitro and in vivo. We also explored how Ga3+ ions inhibited the biofilm formation of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) and osteoclast differentiation. Results The alloy exhibited outstanding antibiofilm properties against both S. aureus and E. coli in vitro and decent antibiofilm performance against S. aureus in vivo. The proteomics results demonstrated that Ga3+ ions could disturb the bacterial Fe metabolism of both S. aureus and E. coli, inhibiting bacterial biofilm formation. In addition, Ti-Ga alloys could inhibit receptor activator of nuclear factor-κB ligand (RANKL)-dependent osteoclast differentiation and function by targeting iron metabolism, then suppressing the activation of the NF-κB signaling pathway, thus, showing their potential to prevent aseptic loosening. Conclusion This study provides an advanced Ti-Ga alloy that can be used as a promising orthopedic implant raw material for various clinical scenarios. This work also revealed that iron metabolism is the common target of Ga3+ ions to inhibit biofilm formation and osteoclast differentiation

Benzo-Extended Cyclohepta[def]fluorene Derivatives with Very Low-Lying Triplet States

Open-shell non-alternant polycyclic hydrocarbons (PHs) are attracting increasing attention due to their promising applications in organic spintronics and quantum computing. Herein we report the synthesis of three cyclohepta[def]fluorene-based diradicaloids (1–3), by fusion of benzo rings on its periphery for the thermodynamic stabilization, as evidenced by multiple characterization techniques. Remarkably, all of them display a very narrow optical energy gap (Egopt=0.52–0.69 eV) and persistent stability under ambient conditions (t1/2=11.7–33.3 h). More importantly, this new type of diradicaloids possess a low-lying triplet state with an extremely small singlet–triplet energy gap, as low as 0.002 kcal mol−1, with a clear dependence on the molecular size. This family of compounds thus offers a new route to create non-alternant open-shell PHs with high-spin ground states, and opens up novel possibilities and insights into understanding the structure–property relationships