Structure-based design and synthesis of anti-fibrotic compounds derived from para-positioned 3,4,5-trisubstituted benzene.

Liver fibrosis is an abnormal wound-healing response to liver injuries. It can lead to liver cirrhosis, and even liver cancer and liver failure. There is a lack of treatment for liver fibrosis and it is of great importance to develop anti-fibrotic drugs.

Mandibular advancement with clear aligners and functional appliances in the treatment of skeletal ClassⅡmalocclusion: a systematic review and meta-analysis.

Objectives: This study aimed to conduct a meta-analysis of the efficacy of mandibular advance clear alig-ners with traditional functional appliances as the control group.

Methods: PubMed, Web of Science, Embase, Cochrane Library, China Biomedical Abstracts Database, China Knowledge Network Database, Wanfang Database, and Weipu Database were used in this study. The two groups of researchers screened the literature and extracted data based on the inclusion and exclusion criteria established by PICOS entries, and used the ROBINS-I scale for quality evaluation.

Structural insights into the redox regulation of Oncomelania hupensis TRP14 and its potential role in the snail host response to parasite invasion.

The freshwater amphibious snail Oncomelania hupensis is the unique intermediate host of Schistosoma japonicum, but little attention has been paid to the interaction between the two. In snails, the production of reactive oxygen species (ROS) by hemocytes has been shown to be vital for snail immune defense against schistosome infection. However, excessive ROS accumulation could lead to oxidative damage, requiring the antioxidant system for maintaining the cellular redox homeostasis.

[Diffusive Fluxes and Controls of NO from Coastal Rivers in Tianjin City].

Rivers are an important emission source of greenhouse gases. To explore the spatial characteristics and influencing factors of NO emission from the coastal rivers in Tianjin City, six rivers into the Bohai Sea from different land-use types were selected, and the NO concentrations, saturation, and diffusive fluxes were measured using the headspace-gas chromatography method. The NO concentration was in supersaturation, and the rivers were the source of atmospheric NO.

Overexpression of phosphatidylethanolamine-binding protein 4 (PEBP4) associates with recurrence of meningiomas.

Background And Purpose: Abnormal expression of phosphatidylethanolamine-binding protein 4 (PEBP4) has been identified in various types of malignant tumors. In the present study, we investigated the expression of PEBP4 in meningioma cases and examined whether PEBP4 expression was correlated with outcomes among these patients.

Materials And Methods: The expression levels of PEBP4 and Ki-67 in human meningioma tissues from 65 patients were evaluated by immunohistochemical staining.

Clinical efficacy and mechanism of mesenchymal stromal cells in treatment of COVID-19.

Coronavirus disease 2019 (COVID-19) is a highly infectious epidemic disease that has seriously affected human health worldwide. To date, however, there is still no definitive drug for the treatment of COVID-19. Cell-based therapies could represent a new breakthrough.

Structural and functional insights into macrophage migration inhibitory factor from Oncomelania hupensis, the intermediate host of Schistosoma japonicum.

Oncomelania hupensis is the unique intermediate host of Schistosoma japonicum. As an irreplaceable prerequisite in the transmission and prevalence of schistosomiasis japonica, an in-depth study of this obligate host-parasite interaction can provide glimpse into the molecular events in the competition between schistosome infectivity and snail immune resistance. In previous studies, we identified a macrophage migration inhibitory factor (MIF) from O.

Phycocomes zhengii gen. nov., sp. nov., a marine bacterium of the family Rhodobacteraceae isolated from the phycosphere of Chlorella vulgaris.

A Gram-stain-negative, motile with flagellum, ovoid- or rod-shaped, aerobic bacterium, was isolated from the phycosphere of the microalga Chlorellavulgaris and designated as strain LMIT002. The bacterium formed white, circular and smooth colonies on marine agar 2216 after 48 h incubation at 25 °C. On the basis of 16S rRNA gene sequence analysis, strain LMIT002 was found to be affiliated with the family Rhodobacteraceae of the order Rhodobacterales, and formed a distinct group.

Knockdown of PEBP4 inhibits human glioma cell growth and invasive potential via ERK1/2 signaling pathway.

Phosphatidylethanolamine (PE)-binding protein 4 (PEBP4) is an antiapoptotic protein that is aberrantly expressed in various malignancies. We previously demonstrated that PEBP4 expression is dramatically induced in human gliomas and positively correlated with tumor grade and patient survival. However, the function of PEBP4 in human glioma development and underlying mechanisms remain largely unknown.

Structure-based optimization of salt-bridge network across the complex interface of PTPN4 PDZ domain with its peptide ligands in neuroglioma.

The PTP non-receptor type 4 (PTPN4) is an important regulator protein in learning, spatial memory and cerebellar synaptic plasticity; targeting the PDZ domain of PTPN4 has become as attractive therapeutic strategy for human neuroglioma. Here, we systematically examined the complex crystal structures of PTPN4 PDZ domain with its known peptide ligands; a number of charged amino acid residues were identified in these ligands and in the peptide-binding pocket of PDZ domain, which can constitute a complicated salt-bridge network across the complex interface. Molecular dynamics (MD) simulations, binding free energy calculations and continuum model analysis revealed that the electrostatic effect plays a predominant role in domain-peptide binding, while other noncovalent interactions such as hydrogen bonds and hydrophobic forces are also responsible for the binding.

Highly water-soluble platinum(II) complexes as GLUT substrates for targeted therapy: improved anticancer efficacy and transporter-mediated cytotoxic properties.

Glucose-conjugated malonato-platinum(II) complexes are designed and synthesized to target tumor-specific active transporters, namely, glucose transporters (GLUTs); the complexes exhibit much higher aqueous solubility by 150 times, improved potency in cytotoxicities by 10 times, and increased therapeutic index by over 30 fold compared to the newest generation of clinical drugs oxaliplatin.

Synthesis, characterization and in vitro anti-tumor activities of matrine derivatives.

Nineteen previously unreported matrine derivatives were synthesized and characterized using elemental analysis, infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, and mass spectrometry. Target compounds 6a-6l and 7a-7c showed stronger inhibitory activities than matrine in the in vitro antitumor tests and inhibited the growth of the Hep7402, B16-F10, A549, and TW03 cell lines. In addition, compound 6i exhibited a potent antitumor activity similar to that of colchicine.

Synthesis of carbazolones and 3-acetylindoles via oxidative C-N bond formation through PIFA-mediated annulation of 2-aryl enaminones.

A series of carbazolone derivatives and 3-acetylindoles have been achieved via PIFA-mediated intramolecular cyclization of 2-aryl enaminones. This process allows the N-moiety on the side-chain to be annulated to the benzene ring via the metal-free oxidative aromatic C-N bond formation.

Pd-catalysed synthesis of isoquinolinones and analogues via C-H and N-H bonds double activation.

An atom economical synthesis of isoquinolinones and analogues via ligand-free Pd-catalysed C-H and N-H double activation has been developed. A series of isoquinolinones were obtained in good to excellent yields. Good regioselectivities were also observed during the activation reactions with unsymmetrical alkynes.

3D pharmacophore models for thromboxane A(2) receptor antagonists.

Thromboxane A(2) (TXA(2)) is an endogenous arachidonic acid derivative closely correlated to thrombosis and other cardiovascular diseases. The action of TXA(2) can be effectively inhibited with TXA(2) receptor antagonists (TXRAs). Previous studies have attempted to describe the interactions between the TXA(2) receptor and its ligands, but their conclusions are still controversial.

3D-pharmacophore models for selective A2A and A2B adenosine receptor antagonists.

Three-dimensional pharmacophore models were generated for A2A and A2B adenosine receptors (ARs) based on highly selective A2A and A2B antagonists using the Catalyst program. The best pharmacophore model for selective A2A antagonists (Hypo-A2A) was obtained through a careful validation process. Four features contained in Hypo-A2A (one ring aromatic feature (R), one positively ionizable feature (P), one hydrogen bond acceptor lipid feature (L), and one hydrophobic feature (H)) seem to be essential for antagonists in terms of binding activity and A2A AR selectivity.

[Effect of photodynamic therapy combined with interstitial chemotherapy for gliomas].

Objective: To investigate the therapeutic effect of photodynamic therapy (PDT) combined with interstitial chemo- therapy on gliomas after microsurgery.

Methods: Twenty-eight patients with glioma received microsurgery for glioma resection as much as possible, during which PDT was carried out and an Ommaya bursa implanted into the cavity left by the resected tumor. PDT was performed again 24 h after the operation and carmustine injected into the Ommaya bursa for interstitial chemotherapy at the different time after the operation.

[Establishment of canine models of penetrating craniocerebral gunshot wound].

Objective: To establish a canine model of penetrating craniocerebral gunshot wound.

Method: Gunshot wound was induced in 54 cross-bred dogs using 7.62-mm pistol bullets fired using a pistol from a distance of 30 cm in coronal direction with a tilt of 10 degrees toward the orbit, causing penetrating craniocerebral injury 1 cm posterior and 1.