Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus that affects approximately half of patients with diabetes. Current treatment regimens cannot treat DPN effectively. ...Schwann cells (SCs) are very sensitive to glucose concentration and insulin, and closely associated with the occurrence and development of type 1 diabetic mellitus (T1DM) and DPN. Apoptosis of SCs is induced by hyperglycemia and is involved in the pathogenesis of DPN. This review considers the pathological processes of SCs apoptosis under high glucose, which include the following: oxidative stress, inflammatory reactions, endoplasmic reticulum stress, autophagy, nitrification and signaling pathways (PI3K/AKT, ERK, PERK/Nrf2, and Wnt/β-catenin). The clarification of mechanisms underlying SCs apoptosis induced by high glucose will help us to understand and identify more effective strategies for the treatment of T1DM DPN.
Display omitted
•The prevalence of anxiety symptom and depressive symptom during the COVID-19 pandemic were relatively high.•The prevalence of anxiety symptom and depressive symptom varies among different countries’ ...college students.•The pooled prevalence of depressive symptom in females was higher compared with males.
The global pandemic of COVID-19 has brought huge changes to people's lifestyles, college students have also been affected seriously. Evidence about these significant changes indicated that college students were more prone to feel anxious and depressed. To derive a precise assessment of the prevalence of anxiety symptom and depressive symptom among college students worldwide, we conducted this meta-analysis.
Based on the guidance of PRISMA, literature was searched in Pubmed, Web of Science, Embase, and PsycArticles (last search November 6, 2020). These articles after the screening were analyzed by a random-effects model to estimate the pooled prevalence of anxiety symptom and depressive symptom. Also, subgroup analysis, sensitivity analysis, and publication bias were performed in this meta-analysis.
The results showed that the pooled anxiety symptom prevalence was 31% (95% CI: 23-39%), pooled depressive symptom prevalence was 34% (95% CI: 27-41%). Subgroup analysis showed that the prevalence of anxiety symptom and depressive symptom among different countries’ college students were different, and the pooled depressive symptom prevalence of females was higher compared with males.
The prevalence of anxiety symptom and depressive symptom in worldwide college students could be better assessed by a standard and reliable questionnaire.
The results suggest that the prevalence of anxiety symptom and depressive symptom during the COVID-19 pandemic is relatively high. Except for interventions that should be taken to control the pandemic urgently, mental health services are also needed to decrease the risk of anxiety and depression among college students.
Saponins are amphiphilic molecules consisting of carbohydrate and either triterpenoid or steroid aglycone moieties and are noted for their multiple biological activities-Fungicidal, antimicrobial, ...antiviral, anti-inflammatory, anticancer, antioxidant and immunomodulatory effects have all been observed. Saponins from natural sources have long been used in herbal and traditional medicines; however, the isolation of complexed saponins from nature is difficult and laborious, due to the scarce amount and structure heterogeneity. Chemical synthesis is considered a powerful tool to expand the structural diversity of saponin, leading to the discovery of promising compounds. This review focuses on recent developments in the structure optimization and biological evaluation of synthetic triterpenoid and steroid saponin derivatives. By summarizing the structure-activity relationship (SAR) results, we hope to provide the direction for future development of saponin-based bioactive compounds.
With the climate constantly changing, plants suffer more frequently from various abiotic and biotic stresses. However, they have evolved biosynthetic machinery to survive in stressful environmental ...conditions. Flavonoids are involved in a variety of biological activities in plants, which can protect plants from different biotic (plant-parasitic nematodes, fungi and bacteria) and abiotic stresses (salt stress, drought stress, UV, higher and lower temperatures). Flavonoids contain several subgroups, including anthocyanidins, flavonols, flavones, flavanols, flavanones, chalcones, dihydrochalcones and dihydroflavonols, which are widely distributed in various plants. As the pathway of flavonoid biosynthesis has been well studied, many researchers have applied transgenic technologies in order to explore the molecular mechanism of genes associated with flavonoid biosynthesis; as such, many transgenic plants have shown a higher stress tolerance through the regulation of flavonoid content. In the present review, the classification, molecular structure and biological biosynthesis of flavonoids were summarized, and the roles of flavonoids under various forms of biotic and abiotic stress in plants were also included. In addition, the effect of applying genes associated with flavonoid biosynthesis on the enhancement of plant tolerance under various biotic and abiotic stresses was also discussed.
Research Summary
Strategic management has seen numerous studies analyzing interaction terms in nonlinear models since Hoetker's (Strat Mgmt J., 2007, 28(4), 331–343) best‐practice recommendations and ...Zelner's (Strat Mgmt J., 2009, 30(12), 1335–1348) simulation‐based approach. We suggest an alternative recentering approach to assess the statistical and economic importance of interaction terms in nonlinear models. Our approach does not rely on making assumptions about the values of the control variables; it takes the existing model and data as is and requires fewer computational steps. The recentering approach not only provides a consistent answer about statistical meaningfulness of the interaction term at a given point of interest, but also helps to assess the effect size using the template that we offer in this study. We demonstrate how to implement our approach and discuss the implications for strategy researchers.
Managerial Summary
In industry settings, the relationship between multiple corporate strategy‐related inputs and corporate performance is often nonlinear in nature. Furthermore, such relationships tend to vary for different types of firms represented within the broader population of firms in a given industry. It is thus imperative for managers to know how to take nonlinear relationships between related business factors into account when they make strategic decisions. We suggest a simple and easily implementable way of assessing and interpreting interactions in a nonlinear setting, which we term a recentering approach. We demonstrate how to apply our approach to a strategic management setting.
Stress reduction through contact with nature is well established, but far less is known about the contribution of contact parameters - duration, frequency, and nature quality. This study describes ...the relationship between duration of a nature experience (NE), and changes in two physiological biomarkers of stress - salivary cortisol and alpha-amylase. It is the first study to employ long-term, repeated-measure assessment and the first evaluation wherein study participants are free to choose the time of day, duration, and the place of a NE in response to personal preference and changing daily schedules. During an 8-week study period, 36 urban dwellers were asked to have a NE, defined as spending time in an outdoor place that brings a sense of contact with nature, at least three times a week for a duration of 10 min or more. Their goal was compliance within the context of unpredictable opportunity for taking a nature pill. Participants provided saliva samples before and after a NE at four points over the study period. Before-NE samples established the diurnal trajectory of each stress indicator and these were in line with published outcomes of more closely controlled experiments. For salivary cortisol, an NE produced a 21.3%/hour drop beyond that of the hormone's 11.7% diurnal drop. The efficiency of a nature pill per time expended was greatest between 20 and 30 min, after which benefits continued to accrue, but at a reduced rate. For salivary alpha-amylase, there was a 28.1%/h drop after adjusting for its diurnal rise of 3.5%/h, but only for participants that were least active sitting or sitting with some walking. Activity type did not influence cortisol response. The methods for this adaptive management study of nature-based restoration break new ground in addressing some complexities of measuring an effective nature dose in the context of normal daily life, while bypassing the limitations of a clinical pharmacology dose-response study. The results provide a validated starting point for healthcare practitioners prescribing a nature pill to those in their care. This line of inquiry is timely in light of expanding urbanization and rising healthcare costs.
The grain boundaries (GBs)/surface defects within perovskite film directly impede the further improvement of photoelectric conversion efficiency (PCE) and stability of planar perovskite solar cells ...(PSCs). Herein, 3D phytic acid (PA) and phytic acid dipotassium (PAD) with polydentate are explored to synchronously passivate the defects of perovskite absorber directly in multiple spatial directions. The strong electron‐donating groups (H2PO4) in the PA molecule afford six anchor sites to bind firmly with uncoordinated Pb2+ at the GBs/surface and modulate perovskite crystallization, thus enhancing the quality of perovskite film. Particularly, PAD containing an additional (K→PO) push–pull structure promotes the dominant coordination of phosphate group (PO) with Pb2+ and passivates halide anion defects due to the complexation of potassium ions (K+) with iodide ions (I‐). Consequently, the PAD‐complexed PSCs deliver a champion PCE of 23.18%, which is remarkably higher than that of the control device (19.94%). Meanwhile, PAD‐complexed PSCs exhibit superior moisture and thermal stability, remaining 79% of their initial PCE after 1000 h under continuous illumination, while the control device remain only 48% of their PCE after 1000 h. This work provides important insights into designing multifunctional 3D passivators for the purpose of simultaneously enhancing the efficiency and stability of devices.
3D polydentate complexing agents are explored to synchronously passivate defects of perovskite absorber directly in multiple spatial directions. The strong electron‐donating groups (H2PO4) in the phytic acid can passivate non‐coordinated Pb2+ at the ground boundaries/surface and modulate perovskite crystallization. Especially, phytic acid dipotassium (PAD) containing additional (K→PO) push–pull structure passivates the amphoteric defects. Therefore, the PAD‐passivated perovskite solar cells deliver a champion photoelectric conversion efficiency of 23.18%.
The effects of intravenous corticosteroids in patients with sepsis remain controversial due to mixed results from randomized trials. Moreover, updated definitions of sepsis, Sepsis-3, were proposed ...in 2016, and findings related to the effects of corticosteroids in patients defined by the Sepsis-3 criteria are scarce.
To investigate the effectiveness of corticosteroids in patients with sepsis or septic shock using real-world data to complement the findings of randomized controlled trials, and to determine whether the treatment effects differ by sepsis definitions.
We conducted this study by utilizing a large, multi-center healthcare database, eICU, in which we identified patients with sepsis admitted to 208 intensive care units across the US from 2014 to 2015 based on two different definitions: prior explicit definitions (i.e., based on diagnosis codes) and the Sepsis-3 definitions (i.e., based on SOFA score). The association between intravenous corticosteroids and in-hospital survival up to 50 days in patients with sepsis was retrospectively analyzed. A parametric hazard model with stabilized inverse probability of treatment weight adjustment was used to control for baseline confounders.
Of the 7,158 patients identified based on the explicit definition, 562 (7.9%) received corticosteroids; of the 5,009 patients identified based on the Sepsis-3 definition, 465 (9.3%) received corticosteroids. In the explicit cohort, adjusted in-hospital survival at day 50 was 0.62 in the treated vs 0.57 in the non-treated, with a survival difference of 0.05 (95%CI: -0.11, 0.17). Similar results were seen in the Sepsis-3 cohort (0.58 vs 0.56 in treated and non-treated, respectively), with a 50-day survival difference of 0.02 (95%CI: -0.19, 0.17).
In patients with sepsis or septic shock, intravenous corticosteroids were not associated with a higher in-hospital survival up to 50 days regardless of the sepsis definitions. Further research may be necessary to definitively confirm effectiveness in real-world practice.
Utilization of laser headspace and near-infrared (NIR) methods provides rapid and non-destructive approaches for moisture detection of lyophilized drug products to facilitate lyophilization ...formulation characterization and process development. In the present study, the NIR method was developed based on a partial least square regression (PLSR) model calibrated and validated with Karl Fisher (KF) data, whereas the laser headspace method was developed with aid of dynamic vapor sorption (DVS) method so that the water vapor pressure measured from the headspace of a lyophilized drug product vial can be converted directly to water content value through the water vapor sorption isotherm of the lyophilized drug product bypassing KF calibration. The water contents of lyophilized samples obtained from both methods agreed well with KF data, with a root mean squared error of prediction (RMSEP) of less than 0.15%. The pros and cons of NIR and laser headspace method were evaluated. The results suggest that traditional off-line KF method can be potentially replaced by at-line laser headspace method combined with water sorption isotherm data from DVS. Further studies may be needed to evaluate the quantitation limit and generality of this method to a variety of lyophilized formulations.
The outbreak of COVID-19 caused by SARS-CoV-2 has resulted in more than 50 million confirmed cases and over 1 million deaths worldwide as of November 2020. Currently, there are no effective ...antivirals approved by the Food and Drug Administration to contain this pandemic except the antiviral agent remdesivir. In addition, the trimeric spike protein on the viral surface is highly glycosylated and almost 200,000 variants with mutations at more than 1,000 positions in its 1,273 amino acid sequence were reported, posing a major challenge in the development of antibodies and vaccines. It is therefore urgently needed to have alternative and timely treatments for the disease. In this study, we used a cell-based infection assay to screen more than 3,000 agents used in humans and animals, including 2,855 small molecules and 190 traditional herbal medicines, and identified 15 active small molecules in concentrations ranging from 0.1 nM to 50 μM. Two enzymatic assays, along with molecular modeling, were then developed to confirm those targeting the virus 3CL protease and the RNA-dependent RNA polymerase. Several water extracts of herbal medicines were active in the cell-based assay and could be further developed as plant-derived anti-SARS-CoV-2 agents. Some of the active compounds identified in the screen were further tested in vivo, and it was found that mefloquine, nelfinavir, and extracts of
(RF3),
, and
were effective in a challenge study using hamsters as disease model.
PDF
