Network pharmacology reveals that Berberine may function against Alzheimer’s disease via the AKT signaling pathway

ObjectiveTo investigate the mechanism underlying the effects of berberine (BBR) in the treatment of Alzheimer’s disease (AD).Methods3 × Tg AD mice were treated with BBR for 3 months, then the open field test (OFT), the novel object recognition test (NOR) and the Morris water maze (MWM) test were performed to assess behavioral performance. Hematoxylin–eosin (HE) staining, Nissl staining were used to examine histopathological changes. The pharmacological and molecular properties of BBR were obtained from the TCMSP database. BBR-associated AD targets were identified using the PharmMapper (PM), the comparative toxicogenomics database (CTD), DisGeNet and the human gene database (GeneCards). Core networks and BBR targets for the treatment of AD were identified using PPI network and functional enrichment analyses. AutoDock software was used to model the interaction between BBR and potential targets. Finally, RT-qPCR, western blotting were used to validate the expression of core targets.ResultsBehavioral experiments, HE staining and Nissl staining have shown that BBR can improve memory task performance and neuronal damage in the hippocampus of AD mice. 117 BBR-associated targets for the treatment of AD were identified, and 43 genes were used for downstream functional enrichment analysis in combination with the results of protein–protein interaction (PPI) network analysis. 2,230 biological processes (BP) terms, 67 cell components (CC) terms, 243 molecular function (MF) terms and 118 KEGG terms were identified. ALB, EGFR, CASP3 and five targets in the PI3K-AKT signaling pathway including AKT1, HSP90AA1, SRC, HRAS, IGF1 were selected by PPI network analysis, validated by molecular docking analysis and RT-q PCR as core targets for further analysis. Akt1 mRNA expression levels were significantly decreased in AD mice and significantly increased after BBR treatment (p < 0.05). Besides, AKT and ERK phosphorylation decreased in the model group, and BBR significantly increased their phosphorylation levels.ConclusionAKT1, HSP90AA1, SRC, HRAS, IGF1 and ALB, EGFR, CASP3 were core targets of BBR in the treatment of AD. BBR may exert a neuroprotective effect by modulating the ERK and AKT signaling pathways

The Psychological Effect of Forming WeChat Groups Between Medical Staff and Patients With COVID-19

Background: This study was conducted in order to explore the effect of psychological intervention based on the use of WeChat with coronavirus disease 2019 (COVID-19) patients.Methods: A total of 65 patients with COVID-19, from two wards, were divided into an experimental group and a control group with the ward as the basic unit. Communication concerning routine treatment and nursing was established between the medical staff and patients in the experimental group via WeChat groups. Within 48 h of admission, at 7 days, and on discharge, all 65 patients completed two self-evaluation questionnaires: the Positive and Negative Affect Schedule (PANAS) and the Hospital Anxiety and Depression Scale (HADS). Hospital stay statistics and a satisfaction survey on discharge were also collated for both groups of patients.Results: The PANAS scores of the experimental group were 26.61 ± 7.99 points on admission, 20.81 ± 5.48 points at 7 days, and 19.58 ± 6.61 points on discharge (P < 0.05). The scores of HADS in the experimental group were 27.74 ± 9.35 points on admission, 12.19 ± 1.92 points at 7 days, and 11.71 ± 3.64 points on discharge (P < 0.05). The differences in the PANS and HADS scores between the experimental and control groups at 7 days and on discharge were statistically significant. The discharge satisfaction ratings of the two groups of patients were 99.87 ± 0.34 and 98.68 ± 1.09 points, the difference being statistically significant (t = 5.827, P < 0.05).Conclusion: Establishing WeChat groups between medical staff and patients with COVID-19 and building a bridge for better communication improved patients' positive mentality and their compliance with doctors, shortened their hospital stay, and promoted their recovery

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

A dataset of tomato fruits images for object detection in the complex lighting environment of plant factories

Plant factories are an advanced form of facility agriculture that enable efficient plant cultivation through controllable environmental conditions, making them highly suitable for the automation and intelligent application of machinery. Tomato cultivation in plant factories has significant economic and agricultural value and can be utilized for various applications such as seedling cultivation, breeding, and genetic engineering. However, manual completion is still required for operations such as detection, counting, and classification of tomato fruits, and the application of machine detection is currently inefficient. Furthermore, research on the automation of tomato harvesting in plant factory environments is limited due to the lack of a suitable dataset. To address this issue, a tomato fruit dataset was constructed for plant factory environments, named as TomatoPlantfactoryDataset, which can be quickly applied to multiple tasks, including the detection of control systems, harvesting robots, yield estimation, and rapid classification and statistics. This dataset features a micro tomato variety and was captured under different artificial lighting conditions, including changes in tomato fruit, complex lighting environment changes, distance changes, occlusion, and blurring. By facilitating the intelligent application of plant factories and the widespread adoption of tomato planting machinery, this dataset can contribute to the detection of intelligent control systems, operation robots, and fruit maturity and yield estimation. The dataset is publicly available for free and can be utilized for research and communication purposes

Two new polyoxomolybdate-based organic–inorganic hybrid compounds with copper ions and bridging ligands

Two new polyoxomolybdate-based organic–inorganic hybrid compounds with copper ions and bridging ligands were prepared in a hydrothermal reaction system, and the chemical formulas are [Cu2(L1)4S][Mo6O19] (1) and [CuIICuI2(L2)5][β-Mo8O26] (2) (L1 = 1,2-bis(iminazole-1-ylmethyl)benzene, L2 = 1,4-bis(1,2,4-triazol-1-ylmethyl)benzene). Complexes 1 and 2 were characterized by elemental analysis, IR spectra, TG analyses and single-crystal X-ray diffraction analyses. Compound 1 exhibits 2-D layers with honeycomb-like cavities, further stacking into a 3-D supramolecular framework with the [Mo6O19]2- polyoxoanions as guest templates in the honeycomb-like cavities. Compound 2 possesses an overall 3D(2D/3D) framework constituted by the undulating 2-D motifs and the 3D sqp framework. The photocatalytic activities of 1 and 2 under UV light were investigated based on the degradation of methylene blue (MB). Both compounds exhibit efficient catalytic activity for the degradation of MB.</p

Surface Electrical Potentials of Root Cell Plasma Membranes: Implications for Ion Interactions, Rhizotoxicity, and Uptake

Many crop plants are exposed to heavy metals and other metals that may intoxicate the crop plants themselves or consumers of the plants. The rhizotoxicity of heavy metals is influenced strongly by the root cell plasma membrane (PM) surface’s electrical potential (ψ0). The usually negative ψ0 is created by negatively charged constituents of the PM. Cations in the rooting medium are attracted to the PM surface and anions are repelled. Addition of ameliorating cations (e.g., Ca2+ and Mg2+) to the rooting medium reduces the effectiveness of cationic toxicants (e.g., Cu2+ and Pb2+) and increases the effectiveness of anionic toxicants (e.g., SeO42− and H2AsO4−). Root growth responses to ions are better correlated with ion activities at PM surfaces ({IZ}0) than with activities in the bulk-phase medium ({IZ}b) (IZ denotes an ion with charge Z). Therefore, electrostatic effects play a role in heavy metal toxicity that may exceed the role of site-specific competition between toxicants and ameliorants. Furthermore, ψ0 controls the transport of ions across the PM by influencing both {IZ}0 and the electrical potential difference across the PM from the outer surface to the inner surface (Em,surf). Em,surf is a component of the driving force for ion fluxes across the PM and controls ion-channel voltage gating. Incorporation of {IZ}0 and Em,surf into quantitative models for root metal toxicity and uptake improves risk assessments of toxic metals in the environment. These risk assessments will improve further with future research on the application of electrostatic theory to heavy metal phytotoxicity in natural soils and aquatic environments

Assessment of the Zn-Co mixtures rhizotoxicity under Ca deficiency: Using two conventional mixture models based on the cell membrane surface potential

Toxicity assessment of Zn-Co mixtures involves multiple ions interactions. The negative potential (ψ0) at the cell membrane surface (CMs) concentrated cationic toxicants (denoted {M2+}0) and influenced the rhizotoxicity of Co2+ or Zn2+. The single and joint rhizotoxicity of Co2+ and Zn2+ to wheat (Triticum aestivum L.) were examined, coupled with different Ca2+ levels. Joint effects of Zn2+, Co2+ and Ca2+ were estimated by the linearly extended concentration addition (CA) and response addition (RA) models. Incorporation of Ca2+ in single metal toxicity assessment significantly enhanced the prediction accuracy (r2 increased from 0.948 to 0.550 for Zn2+ and from 0.903 to 0.611 for Co2+, respectively). ψ0 affected the multiple metals toxicity in both conventional mixture models (r2=0.814 for CA model and 0.820 for RA model). Concretely, {Zn2+}0 alleviated the toxicity of {Co2+}0, while {Co2+}0 had non-significant effect on {Zn2+}0 toxicity. Growth responses to {Ca2+}0 were substantially affected by {Zn2+}0 and {Co2+}0. Ca addition in medium decreased the {M2+}0 by reducing the ψ0 negativity, moreover this addition alleviated Ca deficiency at CMs induced by Zn2+ (or Co2+). These consistent results from both extended CA and RA models indicated that ψ0 provided a novel sight for understanding the rhizotoxicity of multiple metals

Effect of different nitrogen forms on the toxicity of Zn in wheat seedling root: a modeling analysis

Heavy metal stress in culture media is always rhizotoxic. Our study aims to investigate the role of negative potential (ψ) at root cell membrane surface (CMs) on modeling Zn toxicity to wheat seedling roots and to examine the effects of different nitrogen forms (NH and NO ) on ψ and Zn rhizotoxicity. Solution culture experiments were conducted to measure the root elongation and Zn accumulation under Zn exposure. The role of two nitrogen forms in affecting Zn toxicity was compared, giving particular consideration to ψ and Zn activities at CMs ({Zn}). Results showed that NH alleviates Zn rhizotoxicity and NO increases Zn rhizotoxicity. In modeling the rhizotoxicity, root length correlated better with {Zn} than {Zn}, and the predictive accuracy (r) of NH treatment increased from 0.748 to 0.917 when incorporation of {Zn} and {Ca} into analysis. Oppositely, ψ played a limited role in modeling Zn rhizotoxicity and bioavailability in NO treated medium (r\ua0=\ua00.609). Moreover, higher concentration of Zn in roots was found in NO treatment, compared with the NH treatment. ψ rather than the rhizotoxicity data correlated better with Zn accumulation especially in the NO treatment (r\ua0>\ua00.7), which meant the electrical driving force at CMs playing a dominant role in modeling the metal accumulation. In conclusion, the alleviatory role of NH on Zn toxicity and uptake was well explained and modeled by electrostatic effects at CMs. Though our data do not explore mechanisms for the NO -Zn interactions, we propose that ψ worked better in affecting the driving force for root Zn uptake, than influencing metal bioavailability at CMs