Design of Selective PARP-1 Inhibitors and Antitumor Studies.

Designing selective PARP-1 inhibitors has become a new strategy for anticancer drug development. By sequence comparison of PARP-1 and PARP-2, we identified a possible selective site (S site) consisting of several different amino acid residues of α-5 helix and D-loop. Targeting this S site, 140 compounds were designed, synthesized, and characterized for their anticancer activities and mechanisms.

Small Molecule SHP2 Inhibitor LXQ-217 Affects Lung Cancer Cell Proliferation in Vitro and in Vivo.

Background: SHP2 is highly expressed in a variety of cancer and has emerged as a potential target for cancer therapeutic agents. The identification of uncharged pTyr mimics is an important direction for the development of SHP2 orthosteric inhibitors.

Methods: Surface plasmon resonance analysis and cellular thermal shift assay were employed to verify the direct binding of LXQ-217 to SHP2.

MNK, mTOR or eIF4E-selecting the best anti-tumor target for blocking translation initiation.

Overexpression of eIF4E is common in patients with various solid tumors and hematologic cancers. As a potential anti-cancer target, eIF4E has attracted extensive attention from researchers. At the same time, mTOR kinases inhibitors and MNK kinases inhibitors, which are directly related to regulation of eIF4E, have been rapidly developed.

Toward a Treatment of Cancer: Design and In Vitro/In Vivo Evaluation of Uncharged Pyrazoline Derivatives as a Series of Novel SHP2 Inhibitors.

Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2) is a non-receptor protein tyrosine phosphatase (PTP) encoded by the gene, which is involved in the RAS/MAPK cell signaling transduction process. SHP2 has been shown to contribute to the progression of various cancers and is emerging as an important target for anti-tumor drug research. However, past efforts to develop SHP2 inhibitors into drugs have been unsuccessful owing to the positively charged nature of the active site pocket tending to bind negatively charged groups that are usually non-drug-like.

Simultaneous Fluorescence Imaging Reveals -Methyl-d-aspartic Acid Receptor Dependent Zn/H Flux in the Brains of Mice with Depression.

Depression is immensely attributed to the overactivation of -methyl-d-aspartic acid (NMDA) receptor in the brains. As regulatory binding partners of NMDA receptor, both Zn and H are intimately interrelated to NMDA receptor's activity. Therefore, exploring synergistic changes on the levels of Zn and H in brains will promote the knowledge and treatment of depression.

Prediction of K562 Cells Functional Inhibitors Based on Machine Learning Approaches.

Background: β thalassemia is a common monogenic genetic disease that is very harmful to human health. The disease arises is due to the deletion of or defects in β-globin, which reduces synthesis of the β-globin chain, resulting in a relatively excess number of α-chains. The formation of inclusion bodies deposited on the cell membrane causes a decrease in the ability of red blood cells to deform and a group of hereditary haemolytic diseases caused by massive destruction in the spleen.

Patient and Perioperative Factors Influencing the Functional Outcomes and Mortality in Elderly Hip Fractures.

This study aimed to evaluate the functional outcomes and mortality following hip fracture surgery in elderly patients, and to identify the associated risk factors. Between January 2016 and December 2017, 480 consecutive patients were finally included for data analyses. The Harris score and Barthel index were used to evaluate the hip function and ability to perform activities of daily living (ADL).

Highly Specific Cys Fluorescence Probe for Living Mouse Brain Imaging via Evading Reaction with Other Biothiols.

Depression is characterized by oxidative stress in the brain. As the crucial reductive biothiol, cysteine (Cys) directly regulates the occurrence of oxidative stress in the brain. Despite its significance, the precise exploration of Cys in mouse brains remains a challenge, primarily owing to the limitations of Cys-monitoring tools, especially the interference from unavoidable reaction with other biothiols.

visualization of ozone in the brains of mice with depression phenotypes by using a new near-infrared fluorescence probe.

Ozone (O), one of the reactive oxygen species (ROS), is deeply involved in diseases including depression. However, the lack of appropriate detection methods suitable for the complex biological context of brain impedes uncovering the exact relationship between depression and changes in the O level. Therefore, we developed a near-infrared (NIR) fluorescent probe (ACy7) for the direct visualization of O in mice brains.

Mother-to-child transmission of hepatitis B virus after amniocentesis: A retrospective matched cohort study.

Objective: The objective of this study is to determine whether amniocentesis increases the risk of mother-to-child transmission (MTCT) of hepatitis B virus (HBV) and evaluate risk factors for MTCT.

Methods: One hundred forty-three hepatitis B surface antigen (HBsAg)-positive women with amniocentesis were enrolled into the amniocentesis group. Six hundred five nonamniocentesis cases were matched with amniocentesis cases based on maternal viral loads, antiviral therapy regimens, and delivery dates.

Golgi Apparatus Polarity Indicates Depression-Like Behaviors of Mice Using in Vivo Fluorescence Imaging.

Depression is associated with decreased expression of brain-derived neurotrophic factor (BDNF) which assembled in Golgi apparatus. The changes might be closely related to variation in Golgi apparatus polarity. Thus, developing a nondestructive method to detect polarity in living cells and in vivo can facilitate accurate diagnosis and prognosis of depression.

Two-photon imaging of the endoplasmic reticulum thiol flux in the brains of mice with depression phenotypes.

Depression is a common mental illness with high morbidity and mortality. Mounting evidence suggests that an imbalance of the oxidant-antioxidant defence system is strongly correlated with depression and the dysfunction of the endoplasmic reticulum (ER) is strongly related to the oxidative stress. Therefore, as vital and abundant antioxidants in the ER, biothiols may contribute to the etiology of depression.

Knowledge of and attitudes towards hepatitis B and its transmission from mother to child among pregnant women in Guangdong Province, China.

Background: Hepatitis B virus (HBV) infection remains a serious public health problem worldwide. Mother-to-child transmission (MTCT) of HBV is the major mode of transmission in HBV-endemic areas, including China, where little is known about pregnant women's knowledge of and attitudes towards HBV infection and MTCT.

Methods: A cross-sectional survey, conducted in pregnant women in Guangdong Province, China, measured HBV knowledge and attitudes using a questionnaire, at one tertiary and two rural hospitals.