Novel targeting of PEGylated liposomes for codelivery of TGF-β1 siRNA and four antitubercular drugs to human macrophages for the treatment of mycobacterial infection: a quantitative proteomic study

Tuberculosis (TB) is still a major public health issue in developing countries, and its chemotherapy is compromised by poor drug compliance and severe side effects. This study aimed to synthesize and characterize new multimodal PEGylated liposomes encapsulated with clinically commonly used anti-TB drugs with linkage to small interfering RNA (siRNA) against transforming growth factor-β1 (TGF-β1). The novel NP-siRNA liposomes could target THP-1-derived human macrophages that were the host cells of mycobacterium infection. The biological effects of the NP-siRNA liposomes were evaluated on cell cycle distribution, apoptosis, autophagy, and the gene silencing efficiency of TGF-β1 siRNA in human macrophages. We also explored the proteomic responses to the newly synthesized NP-siRNA liposomes using the stable isotope labeling with amino acids in cell culture approach. The results showed that the multifunctional PEGylated liposomes were successfully synthesized and chemically characterized with a mean size of 265.1 nm. The novel NP-siRNA liposomes functionalized with the anti-TB drugs and TGF-β1 siRNA were endocytosed efficiently by human macrophages as visualized by transmission electron microscopy and scanning electron microscopy. Furthermore, the liposomes showed a low cytotoxicity toward human macrophages. There was no significant effect on cell cycle distribution and apoptosis in THP-1-derived macrophages after drug exposure at concentrations ranging from 2.5 to 62.5 μg/mL. Notably, there was a 6.4-fold increase in the autophagy of human macrophages when treated with the NP-siRNA liposomes at 62.5 μg/mL. In addition, the TGF-β1 and nuclear factor-κB expression levels were downregulated by the NP-siRNA liposomes in THP-1-derived macrophages. The Ingenuity Pathway Analysis data showed that there were over 40 signaling pathways involved in the proteomic responses to NP-siRNA liposome exposure in human macrophages, with 160 proteins mapped. The top five canonical signaling pathways were eukaryotic initiation factor 2 signaling, actin cytoskeleton signaling, remodeling of epithelial adherens junctions, epithelial adherens junction signaling, and Rho GDP-dissociation inhibitor signaling pathways. Collectively, the novel synthetic targeting liposomes represent a promising delivery system for anti-TB drugs to human macrophages with good selectivity and minimal cytotoxicity

Study of the doubly Cabibbo-suppressed decays Ds+→K+K+π−D^+_s\to K^+K^+\pi^- and Ds+→K+K+π−π0D^+_s\to K^+K^+\pi^-\pi^0

Based on 7.33 fb$^{-1}$ of $e^+e^-$ collision data collected at center-of-mass energies between 4.128 and 4.226 GeV with the BESIII detector, the experimental studies of the doubly Cabibbo-suppressed decays $D^+_s\to K^+K^+\pi^-$ and $D^+_s\to K^+K^+\pi^-\pi^0$ are reported. We determine the absolute branching fraction of $D^+_s\to K^+K^+\pi^-$ to be (${1.23^{+0.28}_{-0.25}}({\rm stat})\pm0.06({\rm syst})$) $\times 10^{-4}$. No significant signal of $D^+_s\to K^+K^+\pi^-\pi^0$ is observed and the upper limit on its decay branching fraction at 90\% confidence level is set to be $1.7\times10^{-4}$.Comment: 10 pages, 4 figures, 4 table

Updated measurements of the M1 transition ψ(3686)→γηc(2S)\psi(3686) \to \gamma \eta_{c}(2S) with ηc(2S)→KKˉπ\eta_{c}(2S) \to K \bar{K} \pi

Based on a data sample of $(27.08 \pm 0.14 ) \times 10^8~\psi(3686)$ events collected with the BESIII detector at the BEPCII collider, the M1 transition $\psi(3686) \to \gamma \eta_{c}(2S)$ with $\eta_{c}(2S) \to K\bar{K}\pi$ is studied, where $K\bar{K}\pi$ is $K^{+} K^{-} \pi^{0}$ or $K_{S}^{0}K^{\pm}\pi^{\mp}$. The mass and width of the $\eta_{c}(2S)$ are measured to be $(3637.8 \pm 0.8 (\rm {stat}) \pm 0.2 (\rm {syst}))$ MeV/$c^{2}$ and $(10.5 \pm 1.7 (\rm {stat}) \pm 3.5 (\rm {syst}))$ MeV, respectively. The product branching fraction $\mathcal{B}\left(\psi(3686) \rightarrow \gamma \eta_{c}(2 S)\right) \times \mathcal{B}(\eta_{c}(2 S) \rightarrow K \bar{K} \pi)$ is determined to be $(0.97 \pm 0.06 (\rm {stat}) \pm 0.09 (\rm {syst})) \times 10^{-5}$. Using $\mathcal{BR}(\eta_{c}(2S)\to K\bar{K}\pi)=(1.86^{+0.68}_{-0.49})\%$, we obtain the branching fraction of the radiative transition to be $\mathcal{BR}(\psi(3686) \to \gamma \eta_{c}(2S)) = (5.2 \pm 0.3 (\rm {stat}) \pm 0.5 (\rm {syst}) ^{+1.9}_{-1.4} (extr)) \times 10^{-4}$, where the third uncertainty is due to the quoted $\mathcal{BR}(\eta_{c}(2S) \to K\bar{K}\pi)$

Observation of the Singly Cabibbo-Suppressed Decay Λc+→Σ−K+π+\Lambda_{c}^{+}\to \Sigma^{-}K^{+}\pi^{+}

The singly Cabibbo-suppressed decay $\Lambda_{c}^{+}\to \Sigma^{-}K^{+}\pi^{+}$ is observed for the first time with a statistical significance of $6.4\sigma$ by using 4.5 fb$^{-1}$ of $e^+e^-$ collision data collected at center-of-mass energies between 4.600 and 4.699 GeV with the BESIII detector at BEPCII. The absolute branching fraction of $\Lambda_{c}^{+}\to \Sigma^{-}K^{+}\pi^{+}$ is measured to be $(3.8\pm1.3_{\rm stat}\pm0.2_{\rm syst})\times 10^{-4}$ in a model-independent approach. This is the first observation of a Cabibbo-suppressed $\Lambda_{c}^{+}$ decay involving $\Sigma^-$ in the final state. The ratio of branching fractions between $\Lambda_{c}^{+}\to \Sigma^{-}K^{+}\pi^{+}$ and the Cabibbo-favored decay $\Lambda_{c}^{+}\to \Sigma^- \pi^+\pi^+$ is calculated to be $(0.4 \pm 0.1)s_{c}^{2}$, where $s_{c} \equiv \sin\theta_c = 0.2248$ with $\theta_c$ the Cabibbo mixing angle. This ratio significantly deviates from $1.0s_{c}^{2}$ and provides important information for the understanding of nonfactorization contributions in $\Lambda_{c}^{+}$ decays.Comment: 8 pages, 2 figure

Molecular Characterization of Porcine MMP19 and MMP23B Genes and Its Association with Immune Traits

MMP19 and MMP23B belong to the Matrix metalloproteases (MMPs) family, which are zinc-binding endopeptidases that are capable of degrading various components of the extracellular matrix. They are thought to play important roles in embryonic development, reproduction and tissue remodeling, as well as in cell proliferation, differentiation, migration, angiogenesis, apoptosis and host defense. However, they are poorly understood in pigs. Here, we obtained the full length coding region sequence and genomic sequence of the porcine MMP19 and MMP23B genes and analyzed their genomic structures. The deduced amino acid sequence shares similar precursor protein domains with human and mouse MMP19 and MMP23B protein, respectively. Using IMpRH panel, MMP19 was mapped to SSC5p12-q11 (closely linked to microsatellite DK) and MMP23B was mapped to SSC8q11-q12 (linked to microsatellite Sw2521). Quantitative real-time PCR showed that MMP19 was abundantly expressed in the liver, while MMP23B was strongly expressed in the ovarian and heart. Furthermore, both genes were all expressed increasingly in prenatal skeletal muscle during development. Three SNPs were detected by sequencing and PCR-RFLP methods, and association analysis indicated that C203T at exon 5 of MMP19 has a significant association with the blood parameters WBC (G/L) and IgG2 (mg/mL) (P&#60;0.05), SNP C131T at exon 3 of MMP23B is significantly associated with the blood parameters HGB (g/L) and MCH (P&#60;0.05), and A150G in exon 4 has no significant association with the economic traits in pigs.</p

Manufacturing of graphene based synaptic devices for optoelectronic applications

Neuromorphic computing systems can perform memory and computing tasks in parallel on artificial synaptic devices through simulating synaptic functions, which is promising for breaking the conventional von Neumann bottlenecks at hardware level. Artificial optoelectronic synapses enable the synergistic coupling between optical and electrical signals in synaptic modulation, which opens up an innovative path for effective neuromorphic systems. With the advantages of high mobility, optical transparency, ultrawideband tunability, and environmental stability, graphene has attracted tremendous interest for electronic and optoelectronic applications. Recent progress highlights the significance of implementing graphene into artificial synaptic devices. Herein, to better understand the potential of graphene-based synaptic devices, the fabrication technologies of graphene are first presented. Then, the roles of graphene in various synaptic devices are demonstrated. Furthermore, their typical optoelectronic applications in neuromorphic systems are reviewed. Finally, outlooks for development of synaptic devices based on graphene are proposed. This review will provide a comprehensive understanding of graphene fabrication technologies and graphene-based synaptic device for optoelectronic applications, also present an outlook for development of graphene-based synaptic device in future neuromorphic systems