Comparative Proteomic Analysis of Aqueous Humor Reveals Biochemical Disparities in the Eyes of High Myopic Patients.

Myopia accounts for a significant proportion of visual lesions worldwide and has the potential to progress toward pathological myopia. This study aims to reveal the difference in protein content in aqueous humor between high myopic and nonhigh myopic patients, as well as better understand the dysregulation of proteins in myopic eyes. Aqueous humor was collected for liquid chromatograph mass spectrometer (LC/MS) analysis from 30 individual eyes that underwent phacoemulsification and intraocular lens (IOL) implantation. Results showed that a total of 190 differentially expressed proteins were identified, which revealed their involvement in cell metabolism, immune and inflammatory response, and system and anatomical structure. Further analysis focused on 15 intensively interacted hub proteins, encompassing functions related to complement cascades, lipoprotein metabolism, and fibrin biological function. Subsequent validations demonstrated elevated levels of APOE (apolipoprotein E), C3 (complement 3), and AHSG (α-2-HS-glycoprotein) in the high myopia group (31 eyes of cataracts and 45 eyes of high myopia with cataracts). AHSG had a significant positive correlation with axial length in high myopic patients, with good efficacy in distinguishing between myopic and nonmyopic groups. AHSG may be a potential indicator of the pathological severity and participator in the pathological progress of high myopia. This study depicted differential expression characteristics of aqueous humor in patients with high myopia and provided optional information for further experimental research on exploring the molecular mechanisms and potential therapeutic targets for high myopia. Data are available via ProteomeXchange with the identifier PXD047584.

Springtail-Inspired Superamphiphobic Ordered Nanohoodoo Arrays with Quasi-Doubly Reentrant Structures.

The skin of springtails is well-known for being able to repel water and organic liquids using their hexagonally arranged protrusions with reentrant structures. Here, a method to prepare 100 nm-sized nanohoodoo arrays with quasi-doubly reentrant structures over square centimeters through combining the nanosphere lithography and the template-protected selective reactive ion etching technique is demonstrated. The top size of the nanohoodoos, the intra-nanohoodoo distance, and the height of the nanohoodoos can be readily controlled by the plasma-etching time of the polystyrene (PS) spheres, the size of the PS spheres used, and the reactive ion etching time of silicon. The strong structural control capability allows for the study of the relationship between the nanohoodoo structure and the wetting property. Superamphiphobic nanohoodoo arrays with outstanding water/organic liquid repellent properties are finally obtained. The superamphiphobic and liquid repellent properties endow the nanohoodoo arrays with remarkable self-cleaning performance even using hot water droplets, anti-fogging performance, and the surface-enhanced Raman scattering sensitivity improvement by enriching the analyte molecules on the nanohoodoo arrays. Overall, the simple and massive production of the superamphiphobic nanohoodoo structures will push their practical application processes in diverse fields where wettability and liquid repellency need to be carefully engineered.

Design, synthesis and biological evaluation of novel 2,4-bismorpholinothieno[3,2-d]pyrimidine and 2-morpholinothieno[3,2-d]pyrimidinone derivatives as potent antitumor agents.

To develop novel therapeutic agents with anticancer activities, two series of novel 2,4-bismorpholinyl-thieno[3,2-d]pyrimidine and 2-morpholinothieno[3,2-d]pyrimidinone derivatives were designed, synthesized and evaluated for their biological activities. Among them, compound A12 showed the most potent antitumor activities against HCT116, PC-3, MCF-7, A549 and MDA-MB-231 cell lines with IC50 values of 3.24 µM, 14.37 µM, 7.39 µM, 7.10 µM, and 16.85 µM, respectively. Further explorations in bioactivity were conducted to clarify the anticancer mechanism of compound A12. The results showed that compound A12 obviously inhibited the proliferation of A549 cell lines and decreased mitochondrial membrane potential, which led to the apoptosis of cancer cells and suppressed the migration of tumor cells.

Discovery and rational design of 2-aminopyrimidine-based derivatives targeting Janus kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3).

Herein, with the help of computer-aided drug design (CADD), we describe the structure-based rational drug design, structure-activity relationships, and synthesis of a series of 2-aminopyrimidine derivatives that inhibit both JAK2 and FLT3 kinases. These screening cascades revealed that compound 14l demonstrated the most inhibitory activity with IC50 values of 1.8 and 0.68 nM against JAK2 and FLT3 respectively. 14l also showed potent anti-proliferative activities against HEL (IC50 = 0.84 µM) and Molm-13 (IC50 = 0.019 µM) cell lines, but relatively weak cytotoxicity against K562 and PC-3 cell lines, which proved that it might have high target specificity. In vitro metabolism assay, 14l exhibited moderate stability in RLM (Rat Liver Microsomes) with a half-life time of 31 min. In the cellular context of Molm-13, 14l induced cell cycle arrest in G1/S phase and enhanced apoptosis in a dose-dependent manner. These results indicate that 14l is a promising dual JAK2/FLT3 inhibitor and worthy of further development.

Synthesis and antibacterial evaluation of novel oxazolidinone derivatives containing a piperidinyl moiety.

In this article, a series of novel oxazolidinone derivatives containing a piperidinyl moiety was designed and synthesized. Their antibacterial activities were measured against S. aureus, MRSA, MSSA, LREF and VRE by MIC assay. Most of them exhibited potent activity against Gram-positive pathogens comparable to linezolid. Among them, compound 9h exhibited comparable activity with linezolid against human MAO-A for safety evaluation and showed moderate metabolism in human liver microsome. The most promising compound 9h, which showed remarkable antibacterial activity against S. aureus, MRSA, MSSA, LREF and VRE pathogens with MIC value of 0.25-1 µg/mL, was an interesting candidate for further investigation.

Near-Infrared Light-Triggered Porous AuPd Alloy Nanoparticles To Produce Mild Localized Heat To Accelerate Bone Regeneration.

The treatment of massive bone defects is still a significant challenge for orthopedists. Here we have engineered synthetic porous AuPd alloy nanoparticles (pAuPds) as a hyperthermia agent for in situ bone regeneration through photothermal therapy (PTT). After being swallowed by cells, pAuPds produced a mild localized heat (MLH) (40-43 °C) under the irradiation of a near-infrared laser, which can greatly accelerate cell proliferation and bone regeneration. Almost 97% of the cranial defect area (8 mm in diameter) was covered by the newly formed bone after 6 weeks of PTT. RNA sequencing analysis was used to obtain insight into the molecular mechanism of the MLH on cell proliferation and bone formation. These results demonstrated that the Wnt signaling pathway was involved in the MLH. This Letter provides a unique strategy with mild heat stimulation and high efficiency for in situ bone regeneration.

Discovery of 4-piperazinyl-2-aminopyrimidine derivatives as dual inhibitors of JAK2 and FLT3.

Hybridization strategy is an effective strategy to obtain multi-target inhibitors in drug design. In this study, we assembled the pharmacophores of momelotinib and tandutinib to get a series of 4-piperazinyl-2-aminopyrimidine derivatives. All compounds were tested for the inhibition of JAK2 and FLT3 enzymes, of which, compounds with potent enzyme activities were assayed for antiproliferative activities against three cancer cell lines (HEL, MV4-11, and HL60). The structure-activity relationship studies were conducted through variations in two regions, the "A" phenyl ring and "B" phenyl ring. Compound 14j showed the most balanced in vitro inhibitory activity against JAK2 and FLT3 (JAK2 IC50 = 27 nM, FLT3 IC50 = 30 nM), and it also showed potent inhibition against the above tested cell lines. In the cellular context, 14j strongly induced apoptosis by arresting cell cycle in the G1/S phase, and was selected as a promising JAK2/FLT3 dual inhibitor.

Ultrasensitive Au Nanooctahedron Micropinball Sensor for Mercury Ions.

Mercury ion (Hg2+) is one of the most toxic heavy metals that has severe adverse effects on the environment and human organs even at very low concentrations. Therefore, highly sensitive and selective detection of Hg2+ is desirable. Here, we introduce plasmonic micropinball constructed from Au nanooctahedron as a three-dimensional surface-enhanced Raman spectroscopy (SERS) platform, enabling ultrasensitive detection of trace Hg2+ ions. Typically, strong SERS signals could be obtained when the single-stranded DNA structure converts to the hairpin structure in the presence of Hg2+ ions, due to the formation of thymine (T)-Hg2+-T. As a result, the detection limit of Hg2+ ions is as low as 1 × 10-16 M, which is far below compared to that reported for conventional analytical strategies. Moreover, to achieve rapid multiple detection, we combine the micropinball sensors with microflow tube online detection. Our platform prevents cross-talk and tube contamination, allowing multiassay analysis, rapid identification, and quantification of different analytes and concentrations across separate phases.

Synthesis and optical properties of gold nanorods with controllable morphology.

Searching for architectural building blocks with tunable morphology and peculiarity is a prominent challenge for novel diagnostic and therapeutic applications. Here, the aqueous-based seed-mediated methods for preparing highly mono-dispersed Au nanorods with a different aspect ratio are systematically studied by controlling the amounts of Ag ions and seeds. We also explore the effect of pH on the synthesis of gold nanorods. The realization of the overlap of longitudinal plasmon band and excitation source with different degrees is made by changing the aspect ratio of nanorod in order to determine its effect on the overall surface enhancement. In addition, the gold octahedra are prepared by overgrowth on Au nanorods. The SERS effects of Au nanorods are researched and the FDTD simulations are performed to reveal the morphology induced plasmon modes.

Comparative study of microwave radiation-induced magnetoresistive oscillations induced by circularly- and linearly- polarized photo-excitation.

A comparative study of the radiation-induced magnetoresistance oscillations in the high mobility GaAs/AlGaAs heterostructure two dimensional electron system (2DES) under linearly- and circularly- polarized microwave excitation indicates a profound difference in the response observed upon rotating the microwave launcher for the two cases, although circularly polarized microwave radiation induced magnetoresistance oscillations observed at low magnetic fields are similar to the oscillations observed with linearly polarized radiation. For the linearly polarized radiation, the magnetoresistive response is a strong sinusoidal function of the launcher rotation (or linear polarization) angle, θ. For circularly polarized radiation, the oscillatory magnetoresistive response is hardly sensitive to θ.