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Abstract Isofagomine (IFG) and its analogues possess promising glycosidase inhibitory activities. However, a flexible synthetic strategy toward both C5a-functionalized IFGs remains to be explored. Here we show a practical synthesis of C5a-S and R aminomethyl IFG-based derivatives via the diastereoselective addition of cyanide to cyclic nitrone 1. Nitrone 1 was conveniently prepared on a gram scale and in high yield from inexpensive (−)-diethyl d-tartrate via a straightforward method, with a stereoselective Michael addition of a nitroolefin and a Nef reaction as key steps. A 268-membered library (134 × 2) of the C5a-functionalized derivatives was submitted to enzyme- or cell-based bio-evaluations, which resulted in the identification of a promising β-glucocerebrosidase (GCase) stabilizer demonstrating a 2.7-fold enhancement at 25 nM in p.Asn370Ser GCase activity and a 13-fold increase at 1 μM in recombinant human GCase activity in Gaucher cell lines.

Objectives: To explore the association between Internet addiction and suicide ideation, we introduced the Interpersonal Theory of Suicide as a potential model to understand Internet addiction and suicidality. In addition, we intended to identify differences between genders and between subgroups of soldier and student in this association. Methods: We conducted a cross-sectional survey study of 661 participants, comprising military personnel (n = 399, 60.36%) and college students (n = 262, 39.64%). Several copies of anonymous questionnaire were used to assess variables, including Internet addiction, anxiety, depression, perceived burdensomeness, thwarted belongingness, acquired capability for suicide, and suicide ideation. Results: We found that 18% of participants (119 out of 661) met the criteria for Internet addiction. Internet addiction was significantly associated with higher anxiety (p < 0.001), significantly more severe depression (p < 0.001), significantly more perceived burdensomeness (p < 0.001), and significantly more perceived suicidal ideation (p < 0.001). Significant differences in study participants existed in genders (p < 0.001) and between the soldier and student groups (p < 0.001). In regression analyses, we found general associations between specific facets of Internet addiction, for example, compulsive use, and components of the interpersonal theory and thwarted belongingness of suicide. Conclusion: Internet addiction is linked to worse mental health and suicidality. Understanding the connections between Internet addiction and models such as the Interpersonal Theory of Suicide can inform prevention and treatment approaches for vulnerable groups.

BackgroundThis study aimed to report a case who was treated with corticosteroids and anti- parasitic agents for ocular toxoplasmosis, but who progressed to acute retinal necrosis, and finally retinal detachment.Case PresentationA 42-year-old man presented to the ophthalmology clinic with a 1-month history of progressive blurred vision and floaters in his right eye. His best visual acuity (VA) was 20/20 in both eyes. The anterior segment was unremarkable. Funduscopic examination of the right eye revealed active lesions of whitish foci of chorioretinitis with surrounding edema along the superonasal vessels, and retinal vasculitis with perivascular sheathing. Serologic testing was positive for Toxoplasma gondii IgM and IgG, but negative for other virus- and syphilis infections. Ocular toxoplasmosis was diagnosed. Corticosteroids and anti-parasitic agents were given simultaneously, but his right eye VA became 20/100. Funduscopic examination revealed retinal necrosis with localized retinal breaks. We immediately performed focal photocoagulation, however, his right eye progressed to retinal detachment and required vitrectomy.ConclusionEarly administration of systemic corticosteroids in patients with acquired acute ocular toxoplasmosis may lead to complications that impair vision. Intensive observation should be arranged after corticosteroid use.

Key message The complications of endobronchial tuberculosis (TB) include bronchostenosis and fistula. We highly recommend that a TB test be included in the diagnosis of endobronchial lesions.

Impaired wound healing is an ongoing issue that cancer patients undergoing chemotherapy or radiotherapy face. Our previous study regarding lung-cancer-associated pleural fluid (LCPF) demonstrated its propensity to promote endothelial proliferation, migration, and angiogenesis, which are crucial features during cutaneous wound healing. Therefore, the current study aimed to investigate the effect of pleural fluid on cutaneous wound closure in vitro and in vivo using HaCaT keratinocytes and a full-thickness skin wound model, respectively. Both heart-failure-associated pleural fluid (HFPF) and LCPF were sequentially centrifuged and filtered to obtain a cell-free status. Treatment with HFPF and LCPF homogeneously induced HaCaT proliferation with cell cycle progression, migration, and MMP2 upregulation. Western blotting revealed increased PI3K/Akt phosphorylation and VEGFR2/VEGFA expression in HaCaT cells. When treated with the PI3K inhibitor, LCPF-induced keratinocyte proliferation was attenuated with decreased pS6 levels. By applying the VEGFR2 inhibitor, LCPF-induced keratinocyte proliferation was ameliorated by pS6 and MMP2 downregulation. The effect of LCPF-induced cell junction rearrangement was disrupted by co-treatment with a VEGFR2 inhibitor. Compared with a 0.9% saline dressing, LCPF significantly accelerated wound closure and re-epithelization when used as a dressing material in a full-thickness wound model. Histological analysis revealed increased neo-epidermis thickness and dermis collagen synthesis in the LCPF-treated group. Furthermore, LCPF treatment activated basal keratinocytes at the wound edge with the upregulation of Ki-67, VEGFA, and MMP2. Our preliminaries provided the benefit of wet dressing with pleural fluid to improve cutaneous wound closure through enhanced re-epithelization and disclosed future autologous application in cancer wound treatment.

There are many high-power electrical cables around and within semiconductor foundries. These cables are the source of extremely low-frequency (ELF < 300 Hz) magnetic fields that affect the tools which operate by the function of electronic beams. Miss operation (MO) happens because the ELF magnetic fields induce beam shift during the measurement or process for cutting-edge chips below 40 nm. We present the optimal permutation of power transmission lines to reduce electromagnetic influence in high-technology nano fabs. In this study, the magnetic field was reduced using a mirror array power cable system, and simulation results predicted the best permutations to decrease the electromagnetic interference (EMI) value to below 0.4 mG in a working space without any shielding. Furthermore, this innovative method will lower the cost of high-technology nano fabs, especially for the 28 nm process. The motivation behind this paper is to find the ideal permutation of power transmission lines with a three-phase, four-cable framework to decrease the EMI in high-technology nano fabs. In this study, the electromagnetic interference was diminished using the ideal-permutation methodology without investing or using additional energy, labor, or apparatus. Moreover, this advanced methodology will help increase the effectiveness and reduce the costs of nano fabs. The mathematical and experimental results of the study are presented with analysis.