Abstract
The purpose of this study was to examine the changes in severity of anxiety and depression symptoms, stress and sleeping quality after three months of mass quarantine for COVID-19 among ...undergraduate fresh students compared to their pre-COVID-19 measures. We used participants from the Chinese Undergraduate Cohort (CUC), a national prospective longitudinal study to examine the changes in anxiety and depression symptoms severity, stress and sleep quality after being under mass quarantine for three months. Wilcoxon matched pair signed-rank test was used to compare the lifestyle indicators. Severity of anxiety, depression symptoms, stress and sleep quality were compared with Wilcoxon signed-rank test. We used generalized estimating equation (GEE) to further quantify the change in mental health indicators and sleep quality after the COVID-19 mass quarantine compared to baseline. This study found that there was no deterioration in mental health status among Chinese new undergraduate students in 2020 after COVID-19 mass quarantine compared with the baseline measures in 2019. There was an improvement in sleep quality and anxiety symptoms. After adjusting for age, sex, exercise habit, time spent on mobile gadgets, and time spent outdoors, year 2020 was significantly associated with severity of depression symptoms in males (OR:1.52. 95%CI:1.05–2.20,
p
-value = 0.027). Year 2020 was significantly associated with the improvement of sleeping quality in total (OR:0.45, 95%CI:0.38–0.52,
p
< 0.001) and in all the subgroups. This longitudinal study found no deterioration in mental health status among Chinese new undergraduate students after three months of mass quarantine for COVID-19.
Ym1 is a rodent-specific chitinase-like protein (CLP) lacking catalytic activity, whose cellular origins are mainly macrophages, neutrophils and other cells. Although the detailed function of Ym1 ...remains poorly understood, Ym1 has been generally recognized as a fundamental feature of alternative activation of macrophages in mice and hence one of the prevalent detecting targets in macrophage phenotype distinguishment. Studies have pointed out that Ym1 may have regulatory effects, which are multifaceted and even contradictory, far more than just a mere marker. Allergic lung inflammation, parasite infection, autoimmune diseases, and central nervous system diseases have been found associations with Ym1 to varying degrees. Thus, insights into Ym1’s role in diseases would help us understand the pathogenesis of different diseases and clarify the genuine roles of CLPs in mammals. This review summarizes the information on Ym1 from the gene to its expression and regulation and focuses on the association between Ym1 and diseases.
Nanobodies are antibody fragments derived from camelids, naturally endowed with properties like low molecular weight, high affinity and low immunogenicity, which contribute to their effective use as ...research tools, but also as diagnostic and therapeutic agents in a wide range of diseases, including brain diseases. Also, with the success of Caplacizumab, the first approved nanobody drug which was established as a first-in-class medication to treat acquired thrombotic thrombocytopenic purpura, nanobody-based therapy has received increasing attention. In the current review, we first briefly introduce the characterization and manufacturing of nanobodies. Then, we discuss the issue of crossing of the brain-blood-barrier (BBB) by nanobodies, making use of natural methods of BBB penetration, including passive diffusion, active efflux carriers (ATP-binding cassette transporters), carrier-mediated influx
via
solute carriers and transcytosis (including receptor-mediated transport, and adsorptive mediated transport) as well as various physical and chemical methods or even more complicated methods such as genetic methods
via
viral vectors to deliver nanobodies to the brain. Next, we give an extensive overview of research, diagnostic and therapeutic applications of nanobodies in brain-related diseases, with emphasis on Alzheimer’s disease, Parkinson’s disease, and brain tumors. Thanks to the advance of nanobody engineering and modification technologies, nanobodies can be linked to toxins or conjugated with radionuclides, photosensitizers and nanoparticles, according to different requirements. Finally, we provide several perspectives that may facilitate future studies and whereby the versatile nanobodies offer promising perspectives for advancing our knowledge about brain disorders, as well as hopefully yielding diagnostic and therapeutic solutions.
Both C19 and C34 spiroketal domains of okadaic acid were assembled using gold(I) chloride catalyzed spiroketalizations, and the two resulting fragments were coupled to give the C15-C38 fragment of ...okadaic acid, a known intermediate for the total synthesis of this important natural product.
Okadaic acid (OA) and the closely related dinophysistoxins (DTXs) are algal toxins that accumulate in shellfish and are known serine/threonine protein phosphatase (ser/thr PP) inhibitors. ...Phosphatases are important modulators of enzyme activity and cell signaling pathways. However, the interactions between the OA/DTX toxins and phosphatases are not fully understood. This study sought to identify phosphatase targets and characterize their structure-activity relationships (SAR) with these algal toxins using a combination of phosphatase activity and cytotoxicity assays. Preliminary screening of 21 human and yeast phosphatases indicated that only three ser/thr PPs (PP2a, PP1, PP5) were inhibited by physiologically saturating concentrations of DTX2 (200 nM). SAR studies employed naturally-isolated OA, DTX1, and DTX2, which vary in degree and/or position of methylation, in addition to synthetic 2-
-DTX2. OA/DTX analogs induced cytotoxicity and inhibited PP activity with a relatively conserved order of potency: OA = DTX1 ≥ DTX2 >> 2-
-DTX. The PPs were also differentially inhibited with sensitivities of PP2a > PP5 > PP1. These findings demonstrate that small variations in OA/DTX toxin structures, particularly at the head region (i.e., C1/C2), result in significant changes in toxicological potency, whereas changes in methylation at C31 and C35 (tail region) only mildly affect potency. In addition to this being the first study to extensively test OA/DTX analogs' activities towards PP5, these data will be helpful for accurately determining toxic equivalence factors (TEFs), facilitating molecular modeling efforts, and developing highly selective phosphatase inhibitors.
The first total syntheses of the title compounds highlight novel assemblies of the C1–C14 and C28–C38 domains, including an unexpected diastereoselectivity in the Sharpless asymmetric dihydroxylation ...of an alkene at C1C2. PPase inhibition assays revealed that 2‐epi‐DTX‐2 is at least 1 to 2 orders of magnitude less potent than DTX‐2, thus indicating that the configuration at C2 in DTX‐2 is crucial for potent inhibition (see picture).
The thesis described here is synthetic effort towards marine natural PP1 and 2A inhibitor dinophysistoxin-2 (DTX-2) and its unnatural analogues. The first total synthesis of DTX-2 is completed here, ...which applies the previously developed coupling strategies and features a newly designed synthetic access to C1-C14 and C28-C38 segments. Sharpless Asymmetric Dihydroxylation (SAD) is applied to install the C2 stereochemistry, which gives unexpected diastereoselectivity and leads to the synthesis of 2-epi-DTX-2. 2-epi -DTX-2 exhibits greatly reduced potency towards PP1 and 2A, which indicated that the stereochemistry of C2 is crucial to the potency of DTX-2. To fully elucidate the structural basis of DTX-2’s inhibition to PP1 and 2A, a set of analogues is designed based upon preliminary SAR studies and X-ray crystal structure of DTX-2 bound to PP1 and 2A. C8 spiroketal moities of the shared 7-deoxy C1-C14 domain of DTX-2 is prepared via gold (I) catalyzed dehydro-spiroketalization process, which provides a rapid access to the designed analogues of DTX-2.
Die ersten Totalsynthesen der Titelverbindungen nutzten einen neuartigen Aufbau der Einheiten C1–C14 und C28–C38 mit einer unerwarteten Diastereoselektivität der asymmetrischen ...Sharpless‐Dihydroxylierung eines C1C2‐Alkens. 2‐epi‐DTX‐2 erwies sich bei der PPase‐Inhibierung als mindestens ein bis zwei Größenordnungen weniger effektiv als DTX‐2, was auf eine entscheidende Rolle der C2‐Konfiguration in DTX‐2 hinweist (siehe Bild).
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