Physical modeling and geometric shape simulation for one-dimensional flexible objects with cylindrical surface constraints.

This study develops forces equilibrium differential equations for the geometric modeling of 1D flexible objects with surface constraints. These second-order equations are an extension of the Cosserat elastic rod theory and include both bending and torsion. Variables were established for the centerline and attitude in the Cartesian coordinate system of the cross section. This paper specifically investigates the case of a 1D flexible object constrained by a cylindrical surface. To solve this problem, a novel hybrid semi-analytical numerical method is proposed. In this process, a Hamiltonian function and an initial integral operator are introduced in a cylindrical coordinate system. The analytical solution, decoupled in polar coordinates, is then derived. The improved finite difference method was then used to obtain three cylindrical coordinates, which ensured numerical stability and efficiency. The results of a geometric shape simulation with differing boundary conditions demonstrate that this proposed method is capable of real-time modeling. As such, this technique could be a promising new tool for use in graphics simulations of elongated structures, such as DNA molecules, drill pipes, and submarine cables.

A study on the accuracy of a new fluorescent detection method for vaginal fungi.

BACKGROUND: To investigate the positive rate and clinical applicability of liquid-based fungal method for detecting of vaginal fungi. We collect the secretions from the posterior vaginal fornix and the vaginal wall of 198 patients with clinically suspected fungi vaginitis patients for study. METHODS: The vaginal fungi of vaginal discharge were detected by fluorescence method, i.e., by liquid-based thin-layer fungi fluorescence morphology staining detection kit (liquid-based fungal method), saline smear method and fungal culture method. RESULTS: The positive rate of liquid-based fungal method, saline smear method was 50%, 25.75% respectively. The positive rate of liquid-based fungal method were 50%. The true positive rate of liquid-based fungal method (87.85%) was higher than that of saline smear method (45.79%, P < 0.001), which was easy to miss diagnosis. Moreover, the Kappa (K) of liquid-based fungal method was 0.81, and P < 0.01, which was statistically significant, indicating that the consistency of the two detection methods is good. Of the eight common symptoms of fungal vaginitis, the positive symptom coincidence rate of liquid-based fungal method was consistent with that of fungal culture method. It was also easier to see fungi under a microscope than with saline smear method. CONCLUSION: The liquid-based fungal method has a high positive coincidence rate and accuracy in the detection of vaginal fungi, and it is convenient to operate and implement steps. Therefore, it may be applied in clinical practice. Or a combination of several detection methods can be used.

Computer-aided optimal design for flexible cable in aerospace products based on dynamic analogy modeling.

Due to large, complex deformations, the accurate design of cables has become a major problem in the manufacturing of aerospace products. The current design method often leads to large products, uncertain centroids, and poor reliability. To solve these problems, a computer-aided optimal design method for flexible cables was proposed based on dynamic analogy modeling. A nonlinear optimization model was established by combining Cosserat theory and the minimum potential energy principle. The total deformation energy was considered as the optimization object, and Euler parameters were used as control variables to describe the cable geometric shape. Considering the length and bending radius requirements, the normalized form of the cable constraints was expressed by the cross-section position and orientation matrix. An efficient method to solve this problem using finite element discretization and the primitive dual interior point method was proposed. A digital wiring module was developed based on an open source geometry kernel system, and a cable geometry test bench was built. To verify our model, a satellite wiring simulation example was implemented using the module, SolidWorks, and the test bench. Our method achieved the optimal design for the cable length and geometric shape. A theoretical and technical foundation for effectively solving the problem of large cable manufacturing errors and realizing the lightweight design of aerospace products was outlined.

Supercoiling Structure-Based Design of a Trimeric Coiled-Coil Peptide with High Potency against HIV-1 and Human ß-Coronavirus Infection.

Hexameric structure formation through packing of three C-terminal helices and an N-terminal trimeric coiled-coil core has been proposed as a general mechanism of class I enveloped virus entry. In this process, the C-terminal helical repeat (HR2) region of viral membrane fusion proteins becomes transiently exposed and accessible to N-terminal helical repeat (HR1) trimer-based fusion inhibitors. Herein, we describe a mimetic of the HIV-1 gp41 HR1 trimer, N3G, as a promising therapeutic against HIV-1 infection. Surprisingly, we found that in addition to protection against HIV-1 infection, N3G was also highly effective in inhibiting infection of human ß-coronaviruses, including MERS-CoV, HCoV-OC43, and SARS-CoV-2, possibly by binding the HR2 region in the spike protein of ß-coronaviruses to block their hexameric structure formation. These studies demonstrate the potential utility of anti-HIV-1 HR1 peptides in inhibiting human ß-coronavirus infection. Moreover, this strategy could be extended to the design of broad-spectrum antivirals based on the supercoiling structure of peptides.

Design, synthesis and biological evaluation of tetrahydroquinoline-based reversible LSD1 inhibitors.

The targeted regulation of LSD1, which is highly expressed in a variety of tumor cells, is a promising cancer therapy strategy. Several LSD1 inhibitors are currently under clinical evaluation, and most of these inhibitors are irreversible. Here, we report the design, synthesis and biochemical evaluation of novel tetrahydroquinoline-based reversible LSD1 inhibitors. Compounds 18s and 18x, which are selective to LSD1 over MAO-A/B, exhibit excellent LSD1 inhibition at the molecular levels with IC50 = 55 nM and 540 nM, respectively. The classic Lineweaver-Burk plots revealed that compound 18s could reversibly bind the LSD1 enzyme in a noncompetitive manner. Molecular docking was used to reveal the potential binding-mode of the compounds and interpret the structure-activity relationships. Furthermore, compounds 18s and 18x significantly inhibited proliferation (IC50 = 1.13 µM and 1.15 µM, respectively) and induced apoptosis in MGC-803 cells with high expression of LSD1. Compound 18x showed acceptable liver microsomal stability. Meanwhile, 18x did not appear to inhibit CYPs at 10 µM in vitro. Remarkably, the oral administration of compound 18x can inhibit the growth of MGC-803 xenograft tumors without significant side effects. Our findings suggest that tetrahydroquinoline-based LSD1 inhibitors deserve further investigation for the treatment of LSD1 overexpressing cancer.

Design, synthesis and biological evaluation of curcumin analogues as novel LSD1 inhibitors.

Histone lysine-specific demethylase 1 (LSD1) was the first discovered histone demethylase. Inactivating LSD1 or downregulating its expression inhibits cancer-cell development, and thus, it is an attractive molecular target for the development of novel cancer therapeutics. In this study, we worked on the structural optimization of natural products and identified 30 novel LSD1 inhibitors. Utilizing a structure-based drug design strategy, we designed and synthesized a series of curcumin analogues that were shown to be potent LSD1 inhibitors in the enzyme assay. Compound WB07 displayed the most potent LSD1 inhibitory activity, with an IC50 value of 0.8 µM. Moreover, WA20 showed an anticlonogenic effect on A549 cells with an IC50 value of 4.4 µM. Molecular docking simulations were also carried out, and the results indicated that the inhibitors bound to the protein active site located around the key residues of Asp555 and Asp556. These findings suggested that compounds WA20 and WB07 are the first curcumin analogue-based LSD1 inhibitors with remarkable A549 suppressive activity, providing a novel scaffold for the development of LSD1 inhibitors.