Red-Light-Driven Atom Transfer Radical Polymerization for High-Throughput Polymer Synthesis in Open Air.

Photoinduced reversible-deactivation radical polymerization (photo-RDRP) techniques offer exceptional control over polymerization, providing access to well-defined polymers and hybrid materials with complex architectures. However, most photo-RDRP methods rely on UV/visible light or photoredox catalysts (PCs), which require complex multistep synthesis. Herein, we present the first example of fully oxygen-tolerant red/NIR-light-mediated photoinduced atom transfer radical polymerization (photo-ATRP) in a high-throughput manner under biologically relevant conditions. The method uses commercially available methylene blue (MB+) as the PC and [X-CuII/TPMA]+ (TPMA = tris(2-pyridylmethyl)amine) complex as the deactivator. The mechanistic study revealed that MB+ undergoes a reductive quenching cycle in the presence of the TPMA ligand used in excess. The formed semireduced MB (MB•) sustains polymerization by regenerating the [CuI/TPMA]+ activator and together with [X-CuII/TPMA]+ provides control over the polymerization. This dual catalytic system exhibited excellent oxygen tolerance, enabling polymerizations with high monomer conversions (>90%) in less than 60 min at low volumes (50-250 µL) and high-throughput synthesis of a library of well-defined polymers and DNA-polymer bioconjugates with narrow molecular weight distributions (D < 1.30) in an open-air 96-well plate. In addition, the broad absorption spectrum of MB+ allowed ATRP to be triggered under UV to NIR irradiation (395-730 nm). This opens avenues for the integration of orthogonal photoinduced reactions. Finally, the MB+/Cu catalysis showed good biocompatibility during polymerization in the presence of cells, which expands the potential applications of this method.

Molecular Cages Self-Assembled by Imine Condensation in Water.

Self-assembly by imine condensation in aqueous media is a formidable task because of the labile nature of imines in the presence of water. Here, by taking advantage of multivalence and ligand preorganization, basket-shaped triscationic cage molecules are self-assembled in high yields in both water and organic solvent, by condensing a hexaformyl and bisamine. These cages, especially the chiral ones, are stable or inert in aqueous solution, that is, no decomposition was observed upon dilution, precipitation, or exposure to competitive amines or aldehydes. Such water-compatibility allows the hosts to take advantage of the hydrophobic effect to accommodate hydrophobic guests. The chiral cage S-23+ selectively binds and distinguishes one of two enantiomers, opening up opportunities for applications such as chiral compound separation. Chiral narcissistic self-sorting and sergeants-and-soldiers effects occur during cage formation when two amino precursors are involved in self-assembly.

Interference of TGF-ß1/Smad7 signal pathway affects myocardial fibrosis in hypertension.

Hypertension can cause myocardial fibrosis, during which tumor growth factor-beta 1 (TGF-ß1) can facilitate myocardial cell proliferation and transition towards myofibroblast (MFB). Smad7 is a negative regulator of TGF-ß1/Smads signal pathway. This study used hypertension rat model to investigate the regulatory role of TGF-ß1/Smad7 signal pathway in myocardial fibrosis. Rat renal hypertension model was established to test collagen volume fraction, myocardial hydroxyl proline content and COL1A1 expression as well as the expression of TGF-ß1 and Smad7. The expressions of TGF-ß1, Smad7, COLA1A1 and α-SMA at certain generations (P2, P4 and P6) were measured in cultured human cardiac fibroblast (HCF) during differentiation towards MFB differentiation. P6 generation HCF was transfected with pIRES2-EGFP-Smad7 and pIRES2-EGFP-blank followed by measuring expressions of TGF-ß1, Smad7, COLA1A1 and α-SMA. Hydroxyl-proline content and collagen volume fraction were compared between Ad-NC and Ad-Smad7 injection groups. Hypertensive rats had significantly elevated collagen volume fraction, hydroxyl proline contents, and expression of COLA1 and TGF-ß1 than Sham group, whilst Smad7 expression was lower. With increased cell passage, HCF showed gradually increased TGF-ß1, COL1A1 and α-SMA expression, plus decreased Smad7 expression. Over-expression of Smad7 remarkably decreased COLA1 and α-SMA expression in HCF. Tail vein injection of Ad-Smad7 decreased both hydroxyl proline and collagen volume fraction. Elevated TGF-ß1 expression and decreased Smad7 expression are found in fibrotic myocardial tissues of hypertensive rats. Over-expression of Smad7 inhibits differentiation of HCF towards MFB cells, thus decreasing myocardial fibrosis in hypertensive rats.

Ketamine inhibits human sperm function by Ca(2+)-related mechanism.

Ketamine, a dissociative anesthetic, which was widely used in human and animal medicine, has become a popular recreational drug, as it can induce hallucinatory effects. Ketamine abuse can cause serious damage to many aspects of the organism, mainly reflected in the nervous system and urinary system. It has also been reported that ketamine can impair the male genital system. However, the detailed effect of ketamine on human spermatozoa remains unclear. Thus, we investigated the in vitro effects of ketamine on human sperm functions, to elucidate the underlying mechanism. Human sperm were treated in vitro with different concentrations of ketamine (0, 0.125, 0.25, 0.5, 1 g/L). The results showed that 0.25-1 g/L ketamine inhibited sperm total motility, progressive motility and linear velocity, in a dose-dependent manner. In addition, the sperm's ability to penetrate viscous medium and the progesterone-induced acrosome reaction were significantly inhibited by ketamine. Ketamine did not affect sperm viability, capacitation and spontaneous acrosome reaction. The intracellular calcium concentration ([Ca(2+)]i), which is a central factor in the regulation of human sperm function, was decreased by ketamine (0.125-1 g/L) in a dose-dependent manner. Furthermore, the currents of the sperm-specific Ca(2+) channel, CatSper, which modulates Ca(2+) influx in sperm, were inhibited by ketamine (0.125-1 g/L) in a dose-dependent manner. Our findings suggest that ketamine induces its toxic effects on human sperm functions by reducing sperm [Ca(2+)]i through inhibition of CatSper channel.

Guest-induced narcissistic self-sorting in water via imine formation.

Two anionic tetrahedral cages were self-assembled as the only observable products in weakly basic water via imine condensation. The success of the high-yielding formation of the cages in water relies on (i) multivalency enhancing the stability of the imine bond and affording these cages water compatibility and (ii) a guest template with a complementary size and geometry that provides a hydrophobic driving force by occupying the corresponding cage cavity. When all four precursors, namely two trisaldehydes and two trisamines, were combined in water, narcissistic self-sorting occurred when both guest templates were present. In organic media where the hydrophobic effect is absent, narcissistic self-sorting did not occur in the analogous cage systems, confirming the importance of guest templates.

Visible-Light Self-Powered Photodetector with High Sensitivity Based on the Type-II Heterostructure of CdPSe3/MoS2.

Transition metal thiophosphates (MTPs) are a group of emerging van der Waals materials with widely tunable band gaps. In the MTP family, CdPSe3 is demonstrated to possess a wide energy band gap and high carrier mobility, making it a potential candidate in optoelectronic applications. Here, we reported photoelectric response behaviors of both CdPSe3- and CdPSe3/MoS2-based photodetectors (noted as CPS and CM, respectively); these showed prominent photoelectric performances, and the latter proved to be significantly superior to the former. These devices exhibited ultralow dark current at a magnitude order of 10-12 A and fine cycle and air stabilities. Compared with CPS, CM demonstrated the highest responsivity (91.12 mA/W) and detectivity (1.74 × 1011 Jones) at 5 V under 425 nm light illumination. Besides, CM showed self-powered photoelectric responses at zero bias, which was attributed to the improved separation efficiency of photogenerated carriers by the built-in electric field at the interface of the p-n junction. This work proves a prospect for the CM device in portable, self-powered optoelectronic device applications.

Poncirin ameliorates cardiac ischemia-reperfusion injury by activating PI3K/AKT/PGC-1α signaling.

Poncirin, a flavonoid glycoside derivative extracted from the fruits of Poncirus trifoliata (trifoliate orange or Chinese bitter orange), has a variety of documented bioactivities, including anti-tumor, anti-inflammatory, and antioxidant effects. Oxidative stress is a major underlying factor in the pathogenesis of cardiac ischemia-reperfusion (I/R) injury. Therefore, we investigated the protective efficacy of poncirin on primary cardiomyocytes subjected to anoxia-reoxygenation (A/R) injury in vitro, and on rat hearts subjected to ischemia-reperfusion (I/R) injury in vivo. Poncirin pretreatment enhanced cardiomyocyte survival, inhibited A/R-induced oxidative stress by upregulating cellular antioxidant capacity, suppressed mitochondrial depolarization, and ultimately inhibited apoptosis. Similarly, systemic poncirin treatment significantly reduced cardiomyocyte apoptosis and infarct size in rat hearts. In addition, activity of the PI3K/AKT/PGC-1α pathway was significantly increased by poncirin pretreatment in both A/R and I/R injury models, while PI3K and PGC-1α inhibitors abolished all poncirin related effects, suggesting that this pathway is essential for the cardioprotective effects of poncirin. Pretreatment with the PGC-1α inhibitor reversed effects of poncirin without affecting p-AKT expression, indicating that PGC-1α is downstream of AKT. In conclusion, both in vitro and in vivo studies suggested that poncirin alleviates cardiac ischemia-reperfusion injury by mitigating oxidative stress, which is dependent on activation of the PI3K/AKT/PGC-1α signaling pathway.

Adropin Improves Radiation-Induced Myocardial Injury via VEGFR2/PI3K/Akt Pathway.

Mediastinal cancer radiotherapy exposes the heart and causes myocardial injury. It is of utmost importance to identify effective prevention and treatment targets. In this study, the regulatory role of adropin (Ad) in radiation-induced myocardial injury (RIMI) was explored in mice. After C57BL/6 mice were administered E0771 cells and received radiotherapy, the effects of exogenous Ad intervention on myocardial fibrosis, apoptosis, microvessel density, oxidative stress, and protein expression levels were observed. The results showed that exogenous Ad effectively improved cardiac function, suppressed oxidative stress, inhibited myocardial fibrosis, reduced myocardial apoptosis, and promoted microangiogenesis in RIMI mice. Ad also downregulated the expression levels of transforming growth factor ß1 (TGF-ß1), NADPH oxidase 4 (NOX4), and cleaved caspase 3 and upregulated the expression of phosphor-endothelial nitric oxide synthase (p-eNOS). However, the above-mentioned effects of Ad were significantly reversed in Ad-/- mice. Radiotherapy resulted in the downregulation of phosphor-vascular endothelial growth factor receptor (p-VEGFR2) and p-Akt in myocardial tissue, which were upregulated by Ad. However, after targeted inhibition of VEGFR2 with apatinib, the effect of Ad on improving RIMI was significantly reversed. Taken together, exogenous Ad significantly ameliorated RIMI by reducing oxidative stress, promoting microangiogenesis, and inhibiting myocardial fibrosis and apoptosis. The underlying molecular mechanism involved may be elucidated by activation of the VEGFR2/PI3K/Akt pathway.

Lidocaine prevents breast cancer growth by targeting neuronatin to inhibit nerve fibers formation.

Lidocaine has been shown to inhibit the invasion and metastasis of breast cancer, but the mechanism still remains unclear. This study explored the relationship between lidocaine and circulating seeding of breast cancer cells from the perspective of nerve fiber formation. The cell lines MDA-MB-231 and 4T1 were subcutaneously inoculated in mice to simulate the tumor self-seeding by circulating cancer cells. Lidocaine was used to treat these mice and tumor growth was observed. Silver staining was performed to observe the distribution of nerve fibers in tumor-bearing tissues, and immunohistochemical analysis was performed to observe the expression levels of nerve-related proteins. The results showed that lidocaine treatment effectively inhibited tumor growth and nerve fiber formation, and down-regulated the expression levels of protein gene product 9.5, neurofilament, nerve growth factor (NGF), and neuronatin (Nnat). Overexpression NGF and Nnat both could reverse the therapeutic effects of lidocaine. These results suggest that the effect of lidocaine on inhibiting breast cancer invasion and metastasis may be achieved by targeting Nnat, regulating the production of NGFs in cancer cells, and subsequently inhibiting the formation of nerve fibers.