Stability of a general adaptive immunity virus dynamics model with multistages of infected cells and two routes of infection

This paper studies an (n+4)-dimensional nonlinear virus dynamics model that characterizes the interactions of the viruses, susceptible host cells, n-stages of infected cells, B cells and cytotoxic T lymphocyte (CTL) cells. Both viral and cellular infections have been incorporated into the model. The infected-susceptible and virus-susceptible infection rates as well as the generation and removal rates of all compartments are described by general nonlinear functions. Five threshold parameters are computed, which insure the existence of the equilibria of the model under consideration. A set of conditions on the general functions has been established, which is sufficient to investigate the global dynamics of the model. The global asymptotic stability of all equilibria is proven by utilizing Lyapunov function and LaSalle's invariance principle. The theoretical results are illustrated by numerical simulations of the model with specific forms of the general functions.     

平板折叠桌的设计模型

根据折叠桌的运动特征,选取折叠桌的四分之一为研究对象,建立任意角度下桌脚点的运动变化模型。考虑到产品稳固性、加工便利性和节约用材三方面对加工参数的影响,对折叠桌进行受力分析,得到多目标组合优化模型,用以确定出折叠桌的最优设计参数。针对用户提出的桌面形状要求,建立桌脚曲线的参数方程。作为模型推广,以椭圆状折叠桌为例,运用Matlab画出了桌脚边缘线在折叠过程中的动态变化示意图。同时,又深入研究Robert van Embricqs的滑动折叠桌,建立了新的桌脚曲线参数方程。最后,运用Matlab对多种形状折叠桌进行仿真,编写多目标优化算法,得出了最优加工参数,并进行了算法描述。     

CONFORMATIONAL PREFERENCES ABOUT Cpy-S BONDS IN DI-2-PYRIDYL DISULFIDE

Abstract

The total energy, dipole moment and electron densities for each possible rotational conformation about the C_py-S bonds of di-2-pyridyl disulfide were evaluated by using the semi-quantitative CNDO/2 method. The conformations in which the pyridine rings are coplanar with the valency plane of the bonded sulfur atom (cis-cis, cis-trans and trans-trans) were predicted to be the most favored ones.

Results of the theoretical study, when compared to some experimental determinations such as dipole moment and variable temperature pmr spectra, provided evidence that easy interconversion between these conformations can occur.     

Negative-pressure wound therapy induces endothelial progenitor cell mobilization in diabetic patients with foot infection or skin defects

Non healing chronic wounds are difficult to treat in patients with diabetes and can result in severe medical problems for these patients and for society. Negative-pressure wound therapy (NPWT) has been adopted to treat intractable chronic wounds and has been reported to be effective. However, the mechanisms underlying the effects of this treatment have not been elucidated. To assess the vasculogenic effect of NPWT, we evaluated the systemic mobilization of endothelial progenitor cells (EPCs) during NPWT. Twenty-two of 29 consecutive patients who presented at the clinic of Seoul National Universty Hospital between December 2009 and November 2010 who underwent NPWT for diabetic foot infections or skin ulcers were included in this study. Peripheral blood samples were taken before NPWT (pre-NPWT) and 7–14 days after the initiation of NPWT (during-NPWT). Fluorescence-activated cell sorting (FACS) analysis showed that the number of cells in EPC-enriched fractions increased after NPWT, and the numbers of EPC colony forming units (CFUs) significantly increased during NPWT. We believe that NPWT is useful for treating patients with diabetic foot infections and skin ulcers, especially when these conditions are accompanied by peripheral arterial insufficiency. The systemic mobilization of EPCs during NPWT may be a mechanism for healing intractable wounds in diabetic patients with foot infections or skin defects via the formation of increased granulation tissue with numerous small blood vessels.     

Monitoring of amoxicilline and ceftazidime in the microdialysate of diabetic foot and serum by capillary electrophoresis with contactless conductivity detection

Determination of the broad-spectrum antibiotics amoxicilline (AMX) and ceftazidime (CTZ) in blood serum and microdialysates of the subcutaneous tissue of the lower limbs is performed using CE with contactless conductivity detection (C⁴D). Baseline separation of AMX is achieved in 0.5 M acetic acid as the background electrolyte and separation of CTZ in 3.2 M acetic acid with addition of 13% v/v methanol. The CE-C⁴D determination is performed in a 25 µm capillary with suppression of the EOF using INST-coating on an effective length of 18 cm and the attained migration time is 4.2 min for AMX and 4.4 min for CTZ. The analysis was performed using 20 µl of serum and 15 µl of microdialysate, treated by the addition of acetonitrile in a ratio of 1/3 v/v and the sample is injected into the capillary using the large volume sample stacking technique. The LOQ attained in the microdialysate is 148 ng/ml for AMX and 339 ng/ml for CTZ, and in serum 143 ng/ml for AMX and 318 ng/ml for CTZ. The CE-C⁴D method is employed for monitoring the passage of AMX and CTZ from the blood circulatory system into the subcutaneous tissue at the sites of diabetic ulceration in patients suffering from diabetic foot syndrome and also for measuring the pharmacokinetics following intravenous application of bolus antibiotic doses.     

Multistep synthesis and screening of heterocyclic tetrads containing furan,pyrazoline, thiazole and triazole (or oxadiazole) as antimicrobial and anticancer agents

In the present study novel heterocyclic tetrads containing furan, pyrazoline, thiazole and triazole (or oxadiazole) (1, 2, 3, 4a-e and 5a-e) were designed and synthesized and investigated for their antimicrobial (against selected bacteria and fungi) and anticancer potential. The molecules 4e and 5e containing 4-fluoro phenyl and 4-fluoro benzyl substituents showed promising antimicrobial (antibacterial and antifungal activities with MICs ranging between 0.5 and 8 µg/mL. Compounds 3 exhibited potent anticancer activity with an IC₅₀ value of 0.49 ± 1.45 µM against the human gastric cancer cell line (BGC-823) whereas compound 4e displayed an IC₅₀ value of 0.65 ± 0.53 µM against breast cancer (MCF-7) cell line respectively. All compounds showed selective toxicity against the cancer cell lines compared to human normal liver cell lines. Molecular docking studies of the most potent compounds (3 and 4e) against selected microbial and cancer proteins revealed the crucial binding interactions of the potent compounds with the target enzymes. Compounds 3 and 4e are promising lead molecules to be developed as potential drug candidates.     

L-Glutamic acid loaded collagen chitosan composite scaffold as regenerative medicine for the accelerated healing of diabetic wounds

Diabetic wounds (DWs) are characterized by prolonged inflammation, which poses a significant challenge for clinicians and researchers to promote healing. In this study, we fabricate L-Glutamic acid (LGA) loaded collagen/chitosan (COL-CS) composite scaffold for the accelerated healing of DW. The characterization outcomes of the composite scaffold revealed that a crosslinked scaffold holds optimum porosity, low matrix degradation, and sustained drug release in contrast to a non-crosslinked scaffold. In vitro, LGA composite scaffolds have not exhibited any toxicity on 3T3L1 cell lines. In vivo, the LGA composite scaffold has shown significantly (p < 0.001), higher rates of wound contraction than those in control and COL-CS scaffold treated groups. In addition, MMP-9 levels were also significantly reduced in LGA composite scaffold-treated group compared with those in the control and COL-CS scaffold treated group. Thus, the LGA composite scaffold may serve as a promising therapy in DW due to its unique modulatory effect on inflammatory biomarker MMP-9.     

Inhibition of two Cu(II) and Mn(II) coordination polymers on the surgical site infections by inhibiting the bacterial biofilm formation

Within this work, two novel Cu(II) and Mn(II)-based coordination polymers (CPs) along with chemical compositions of {[Cu₂(L¹)(1,4-NDC)₂]·3H₂O}_n (1, 1,4-H₂NDC = Naphthalene-1,4-dicarboxylic acid, L¹ ​= ​di(1H-imidazole-1-yl)methane) and [Mn₃(L²)₂(H₂O)₂(1,4-NDC)₂]_n (2, L² ​= ​1,4-di(1H-imidazole-1-yl)benzene) have been completed in success via related metal salts reaction with 1,4-H₂NDC ligand in existence of various N-donor co-ligands. We discovered its application values on the surgical site infections (SSI) along with corresponding mechanism in the interim. We evaluated inflammatory cytokines released into the urine through ELISA detection kit after compound treatment. Then, we discovered the inhibitory effect of compound on the bacterial biofilm formation via real time RT-PCR.     

PET Imaging of Bacterial Infections with Fluorine‐18‐Labeled Maltohexaose

A positron emission tomography (PET) tracer composed of ¹⁸F‐labeled maltohexaose (MH¹⁸F) can image bacteria in vivo with a sensitivity and specificity that are orders of magnitude higher than those of fluorodeoxyglucose (¹⁸FDG). MH¹⁸F can detect early‐stage infections composed of as few as 10⁵ E. coli colony‐forming units (CFUs), and can identify drug resistance in bacteria in vivo. MH¹⁸F has the potential to improve the diagnosis of bacterial infections given its unique combination of high specificity and sensitivity for bacteria.     

NO in Viral Infections: Role and Development of Antiviral Therapies

Nitric oxide is a ubiquitous signaling radical that influences critical body functions. Its importance in the cardiovascular system and the innate immune response to bacterial and viral infections has been extensively investigated. The overproduction of NO is an early component of viral infections, including those affecting the respiratory tract. The production of high levels of NO is due to the overexpression of NO biosynthesis by inducible NO synthase (iNOS), which is involved in viral clearance. The development of NO-based antiviral therapies, particularly gaseous NO inhalation and NO-donors, has proven to be an excellent antiviral therapeutic strategy. The aim of this review is to systematically examine the multiple research studies that have been carried out to elucidate the role of NO in viral infections and to comprehensively describe the NO-based antiviral strategies that have been developed thus far. Particular attention has been paid to the potential mechanisms of NO and its clinical use in the prevention and therapy of COVID-19.