2-Chloro-5-(chloro­meth­yl)pyridine

The title compound, C6H5Cl2N, is almost planar, with an r.m.s. deviation of 0.0146 Å for all atoms except for the 5-choloromethyl Cl atom. The offset Cl atom lies above this plane with a Cl—C—C angle of 111.11 (17)°. In the crystal, mol­ecules are connected via inter­molecular C—H⋯N hydrogen bonds, forming dimers

The thermodynamic and kinetic properties of hydrogen dimers on graphene

The thermodynamic and kinetic properties of hydrogen adatoms on graphene are important to the materials and devices based on hydrogenated graphene. Hydrogen dimers on graphene with coverages varying from 0.040 to 0.111 ML (1.0 ML $= 3.8\times10^{15}$cm$^{-2}$) were considered in this report. The thermodynamic and kinetic properties of H, D and T dimers were studied by ab initio simulations. The vibrational zero-point energy corrections were found to be not negligible in kinetics, varying from 0.038 (0.028, 0.017) to 0.257 (0.187, 0.157) eV for H (D, T) dimers. The isotope effect exhibits as that the kinetic mobility of a hydrogen dimer decreases with increasing the hydrogen mass. The simulated thermal desorption spectra with the heating rate $\alpha = 1.0$ K/s were quite close to experimental measurements. The effect of the interaction between hydrogen dimers on their thermodynamic and kinetic properties were analyzed in detail.Comment: submitted to Surface Scienc

Clinical observation of phacoemulsification and IOL combined with goniosynechialysis for age-related cataract merging with PACG

AIM: To investigate the curative effect of phacoemulsification and intraocular lens(IOL)implantation combined with goniosynechialysis in the treatment of age-related cataract merging with primary angle-closure glaucoma(PACG).METHODS: Totally 80 patients with age-related cataract merging with PACG were in our hospital from January 2014 to January 2016. The preoperative average intraocular pressure(IOP)was 33.22±3.17mmHg; the average depth of anterior chamber was 2.07±0.15mm; the dynamic situation of primary angle closure ≤1/2 cycle by gonioscope. They were randomly divided into Group A and B for doing a study. All the two groups were treated with phacoemulsification and intraocular lens implantation. And the Group A was with goniosynechialysis. The following up period was 2mo, and we observed the IOP, chamber depth and the anterior chamber angle.RESULTS: The change of chamber depth and intraocular pressure about the two groups: the average intraocular pressure of the Group A was 15.11±3.67mmHg,the chamber depth was 3.11±0.08mm; those of the Group B were 17.24±1.67mmHg, 2.76±0.15mm respectively; the differences had statistical significance(PPCONCLUSION: The phacoemulsification and intraocular lens implantation combined with goniosynechialysis in the treatment of age-related cataract merging with primary angle-dosure glaucoma is safe and reliable. It's simple to operate, and do not increase the risk of surgery

Mutant Kras- and p16-regulated NOX4 activation overcomes metabolic checkpoints in development of pancreatic ductal adenocarcinoma

Kras activation and p16 inactivation are required to develop pancreatic ductal adenocarcinoma (PDAC). However, the biochemical mechanisms underlying these double alterations remain unclear. Here we discover that NAD(P)H oxidase 4 (NOX4), an enzyme known to catalyse the oxidation of NAD(P)H, is upregulated when p16 is inactivated by looking at gene expression profiling studies. Activation of NOX4 requires catalytic subunit p22phox, which is upregulated following Kras activation. Both alterations are also detectable in PDAC cell lines and patient specimens. Furthermore, we show that elevated NOX4 activity accelerates oxidation of NADH and supports increased glycolysis by generating NAD+, a substrate for GAPDH-mediated glycolytic reaction, promoting PDAC cell growth. Mechanistically, NOX4 was induced through p16-Rb-regulated E2F and p22phox was induced by KrasG12V-activated NF-κB. In conclusion, we provide a biochemical explanation for the cooperation between p16 inactivation and Kras activation in PDAC development and suggest that NOX4 is a potential therapeutic target for PDAC

A modular assembly of spinal cord-like tissue allows targeted tissue repair in the transected spinal cord

Tissue engineering–based neural construction holds promise in providing organoids with defined differentiation and therapeutic potentials. Here, a bioengineered transplantable spinal cord–like tissue (SCLT) is assembled in vitro by simulating the white matter and gray matter composition of the spinal cord using neural stem cell–based tissue engineering technique. Whether the organoid would execute targeted repair in injured spinal cord is evaluated. The integrated SCLT, assembled by white matter–like tissue (WMLT) module and gray matter–like tissue (GMLT) module, shares architectural, phenotypic, and functional similarities to the adult rat spinal cord. Organotypic coculturing with the dorsal root ganglion or muscle cells shows that the SCLT embraces spinal cord organogenesis potentials to establish connections with the targets, respectively. Transplantation of the SCLT into the transected spinal cord results in a significant motor function recovery of the paralyzed hind limbs in rats. Additionally, targeted spinal cord tissue repair is achieved by the modular design of SCLT, as evidenced by an increased remyelination in the WMLT area and an enlarged innervation in the GMLT area. More importantly, the pro‐regeneration milieu facilitates the formation of a neuronal relay by the donor neurons, allowing the conduction of descending and ascending neural inputs

Yersinia pseudotuberculosis Exploits CD209 Receptors for Promoting Host Dissemination and Infection

Yersinia pseudotuberculosis is a Gram-negative enteropathogen and causes gastrointestinal infections. It disseminates from gut to mesenteric lymph nodes (MLNs), spleen, and liver of infected humans and animals. Although the molecular mechanisms for dissemination and infection are unclear, many Gram-negative enteropathogens presumably invade the small intestine via Peyer's patches to initiate dissemination. In this study, we demonstrate that Y. pseudotuberculosis utilizes its lipopolysaccharide (LPS) core to interact with CD209 receptors, leading to invasion of human dendritic cells (DCs) and murine macrophages. These Y. pseudotuberculosis CD209 interactions result in bacterial dissemination to MLNs, spleens, and livers of both wild-type and Peyer's patch-deficient mice. The blocking of the Y. pseudotuberculosis CD209 interactions by expression of 0-antigen and with oligosaccharides reduces infectivity. Based on the well-documented studies in which HIV-CD209 interaction leads to viral dissemination, we therefore propose an infection route for Y. pseudotuberculosis where this pathogen, after penetrating the intestinal mucosal membrane, hijacks the Y. pseudotuberculosis CD209 interaction antigen-presenting cells to reach their target destinations, MLNs, spleens, and livers.Peer reviewe