Icariside II Ameliorates Cognitive Impairments Induced by Chronic Cerebral Hypoperfusion by Inhibiting the Amyloidogenic Pathway: Involvement of BDNF/TrkB/CREB Signaling and Up-Regulation of PPARα and PPARγ in Rats

Chronic cerebral hypoperfusion (CCH) is regarded as a high-risk factor for cognitive decline of vascular dementia (VD) as it is conducive to induce beta-amyloid (Aβ) aggregation. Icariside II (ICS II), a plant-derived flavonoid compound, has showed neuroprotective effect on animal models of Alzheimer’s disease (AD) by decreasing Aβ levels. Here, we assessed the effect of ICS II on CCH-induced cognitive deficits and Aβ levels in rats, and the possible underlying mechanisms were also explored. It was disclosed that CCH induced by bilateral common carotid artery occlusion (BCCAO) caused cognitive deficits, neuronal injury and increase of Aβ1-40 and Aβ1-42 levels in the rat hippocampus, while oral administration of ICS II for 28 days abolished the above deficits in the hippocampus of BCCAO rats. Meanwhile, ICS II significantly decreased the expression of beta-amyloid precursor protein (APP) and β-site amyloid precursor protein cleavage enzyme 1 (BACE1), as well as increased the expression of a disintegrin and metalloproteinase domain 10 (ADAM10) and insulin-degrading enzyme (IDE). ICS II also activated peroxisome proliferator-activated receptor (PPAR)α and PPARγ, enhanced the expression of brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB), levels of Akt and cAMP response element binding protein (CREB) phosphorylation. Together, these findings suggested that ICS II attenuates CCH-induced cognitive deficits by inhibiting the amyloidogenic pathway via involvement of BDNF/TrkB/CREB signaling and up-regulation of PPARα and PPARγ in rats

Significance of Photosynthetic Characters in the Evolution of Asian Gnetum (Gnetales)

Gnetum is a genus in the Gnetales that has a unique but ambiguous placement within seed plant phylogeny. Previous studies have shown that Gnetum has lower values of photosynthetic characters than those of other seed plants, but few Gnetum species have been studied, and those that have been studied are restricted to narrow taxonomic and geographic ranges. In addition, the mechanism underlying the lower values of photosynthetic characters in Gnetum remains poorly understood. Here, we investigated the photosynthetic characters of a Chinese lianoid species, i.e., Gnetum parvifolium, and co-occurring woody angiosperms growing in the wild, as well as seedlings of five Chinese Gnetum species cultivated in a greenhouse. The five Gnetum species had considerably lower values for photosynthesis parameters (net photosynthetic rate, transpiration rate, intercellular CO2 concentration, and stomatal conductance) than those of other seed plant representatives. Interrelated analyses revealed that the low photosynthetic capacity may be an intrinsic property of Gnetum, and may be associated with its evolutionary history. Comparison of the chloroplast genomes (cpDNAs) of Gnetum with those of other seed plant representatives revealed that 17 coding genes are absent from the cpDNAs of all species of Gnetum. This lack of multiple functional genes from the cpDNAs probably leads to the low photosynthetic rates of Gnetum. Our results provide a new perspective on the evolutionary history of the Gnetales, and on the ecophysiological and genomic attributes of tropical biomes in general. These results could also be useful for the breeding and cultivation of Gnetum

The Role of Long Non-Coding RNAs in Epithelial-Mesenchymal Transition-Related Signaling Pathways in Prostate Cancer

Prostate cancer (PCa) is one of the most common male malignancies with frequent remote invasion and metastasis, leading to high mortality. Epithelial-mesenchymal transition (EMT) is a fundamental process in embryonic development and plays a key role in tumor proliferation, invasion and metastasis. Numerous long non-coding RNAs (lncRNAs) could regulate the occurrence and development of EMT through various complex molecular mechanisms involving multiple signaling pathways in PCa. Given the importance of EMT and lncRNAs in the progression of tumor metastasis, we recapitulate the research progress of EMT-related signaling pathways regulated by lncRNAs in PCa, including AR signaling, STAT3 signaling, Wnt/β-catenin signaling, PTEN/PI3K/AKT signaling, TGF-β/Smad and NF-κB signaling pathways. Furthermore, we summarize four modes of how lncRNAs participate in the EMT process of PCa via regulating relevant signaling pathways

Clinical distribution of carbapenem genotypes and resistance to ceftazidime-avibactam in Enterobacteriaceae bacteria

IntroductionBacterial resistance is a major threat to public health worldwide. To gain an understanding of the clinical infection distribution, drug resistance information, and genotype of CRE in Dongguan, China, as well as the resistance of relevant genotypes to CAZ-AVI, this research aims to improve drug resistance monitoring information in Dongguan and provide a reliable basis for the clinical control and treatment of CRE infection.MethodsVITEK-2 Compact automatic analyzer was utilized to identify 516 strains of CRE collected from January 2017 to June 2023. To determine drug sensitivity, the K-B method, E-test, and MIC methods were used. From June 2022 to June 2023, 80 CRE strains were selected, and GeneXpert Carba-R was used to detect and identify the genotype of the carbapenemase present in the collected CRE strains. An in-depth analysis was conducted on the CAZ-AVI in vitro drug sensitivity activity of various genotypes of CRE, and the results were statistically evaluated using SPSS 23.0 and WHONET 5.6 software.ResultsThis study identified 516 CRE strains, with the majority (70.16%) being K.pneumoniae, followed by E.coli (18.99%). Respiratory specimens had highest detection rate with 53.77% identified, whereas urine specimens had the second highest detection rate with 17.99%. From June 2022 to June 2023, 95% of the strains tested using the CRE GeneXpert Carba-R assay possessed carbapenemase genes, of which 32.5% were blaNDM strains and 61.25% blaKPC strains. The results showed that CRE strains containing blaKPC had a significantly higher rate of resistance to amikacin, cefepime, and aztreonam than those harboring blaNDM.ConclusionsThe CRE strains isolated from Dongguan region demonstrated a high resistance rate to various antibiotics used in clinical practice but a low resistance rate to tigecycline. These strains produce Class A serine carbapenemases and Class B metals β-lactamases, with the majority of them carrying blaNDM and blaKPC. Notably, CRE strains with blaKPC and blaNDM had significantly lower resistance rates to tigecycline. CAZ-AVI showed a good sensitivity rate with no resistance to CRE strains carrying blaKPC. Therefore, CAZ-AVI and tigecycline should be used as a guide for rational use of antibiotics in clinical practice to effectively treat CRE

Muc2 Protects against Lethal Infectious Colitis by Disassociating Pathogenic and Commensal Bacteria from the Colonic Mucosa

Despite recent advances in our understanding of the pathogenesis of attaching and effacing (A/E) Escherichia coli infections, the mechanisms by which the host defends against these microbes are unclear. The goal of this study was to determine the role of goblet cell-derived Muc2, the major intestinal secretory mucin and primary component of the mucus layer, in host protection against A/E pathogens. To assess the role of Muc2 during A/E bacterial infections, we inoculated Muc2 deficient (Muc2−/−) mice with Citrobacter rodentium, a murine A/E pathogen related to diarrheagenic A/E E. coli. Unlike wildtype (WT) mice, infected Muc2−/− mice exhibited rapid weight loss and suffered up to 90% mortality. Stool plating demonstrated 10–100 fold greater C. rodentium burdens in Muc2−/− vs. WT mice, most of which were found to be loosely adherent to the colonic mucosa. Histology of Muc2−/− mice revealed ulceration in the colon amid focal bacterial microcolonies. Metabolic labeling of secreted mucins in the large intestine demonstrated that mucin secretion was markedly increased in WT mice during infection compared to uninfected controls, suggesting that the host uses increased mucin release to flush pathogens from the mucosal surface. Muc2 also impacted host-commensal interactions during infection, as FISH analysis revealed C. rodentium microcolonies contained numerous commensal microbes, which was not observed in WT mice. Orally administered FITC-Dextran and FISH staining showed significantly worsened intestinal barrier disruption in Muc2−/− vs. WT mice, with overt pathogen and commensal translocation into the Muc2−/− colonic mucosa. Interestingly, commensal depletion enhanced C. rodentium colonization of Muc2−/− mice, although colonic pathology was not significantly altered. In conclusion, Muc2 production is critical for host protection during A/E bacterial infections, by limiting overall pathogen and commensal numbers associated with the colonic mucosal surface. Such actions limit tissue damage and translocation of pathogenic and commensal bacteria across the epithelium

Response to first-line erlotinib in a false EGFR mutation-negative patient with non-small-cell lung cancer: Make no assumptions

So far, in the advanced non-small cell lung cancer (NSCLC) with clear epidermal growth factor receptor (EGFR) gene status, the treatment remmendations has reached an agreement: for patients with EGFR mutation-positive, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is the first choice, which can maximize the benefit from the treatment; while for the patients with wild-type EGFR gene, we should give priority to chemotherapy whether in the first-line or second-line therapy. However, about 70% of the patients were diagnosed at the late stage, so the pathological diagnosis and EGFR gene mutation detection depend on small specimens. Due to the limitations of small specimens, it may lead false EGFR mutation-negative, which results in these patients losing the opportunity to receive EGFR-TKI. Therefore, more simple and accessible predictors, in order to discover these potential false negatives of EGFR mutation, are urgently warranted.Here, we report a case showing a positive response to erlotinib treatment in the first-line setting. The patient, an middle-aged male smoker with stage IV NSCLC, had a tumor that was EGFR mutation-negative (wild-type EGFR). Based on this clinical case, we will discuss how to distinguish the false negatives of EGFR mutation and explore the predictors of EGFR mutation-positive , response and survival to EGFR-TKIs in first-line treatment.</p

Characterizing the Status of Energetic Metabolism of Dinoflagellate Resting Cysts under Mock Conditions of Marine Sediments via Physiological and Transcriptional Measurements

Similar to the seeds of higher plants, resting cysts, a non-motile, benthic, and dormant stage in the life history of many dinoflagellate species, play vital roles via germination in the seasonal dynamics and particularly the initiation of harmful algal blooms (HABs) of dinoflagellates. It is thus crucial for resting cysts to balance between the energetic catabolism for viability maintenance and the energy preservation for germination during their dormancy. Despite this importance, studies on how resting cysts of dinoflagellates accomplish energetic metabolism in marine sediment have been virtually absent. In this study, using the cosmopolitan HABs-causing species Scrippsiella acuminata as a representative, we measured the transcriptional activity of the most efficient pathway of the energy catabolism tricarboxylic acid (TCA) cycle, cell viability (via neutral red staining), and the cellular ATP content of resting cysts under a set of mock conditions in marine sediments (e.g., 4 °C, darkness, and anoxia) for a maximum period of one year. Based on the correlation analyses among the expression levels of genes, cyst viability, and ATP content, we revealed that the TCA cycle was still a crucial pathway of energetic catabolism for resting cysts under aerobic conditions, and its expression was elevated at higher temperatures, light irradiation, and the early stage of dormancy. Under anaerobic conditions, however, the TCA cycle pathway ceased expression in resting cysts, as also supported by ATP measurements. Our results have laid a cornerstone for the comprehensive revelation of the energetic metabolism and biochemical processes of dormancy of resting cysts in marine sediments

The Main Evaluation Indicators for the Quality of Fruit Radish

The aim of this study was to establish an scientific evaluation system for fruit radish quality. 8 quality indicators were measured for 23 varieties, such as Meinong, Qiaotouqing and Chunbulao. The indicators included root weight, root shape index, water content, crispness, soluble solids, crude fiber, isothiocyanate and vitamin C. These data were analyzed by variation correlation analysis, principal component analysis and system cluster analysis. 23 varieties of fruit radish were analyzed by variation correlation; 8 indicators were compressed into 6 integrated variables using principal component analysis. Finally, the main evaluation indicators of fruit radish were determined by using cluster analysis and correlation analysis. The results indicated that the range of variation coefficient was from 1.64%—89.99%. Water content, crispness, soluble solids, crude fiber, isothiocyanate were important components of fruit radish quality, playing a major role in the quality. These 8 indicators were closely related and relatively independent. Water content was significantly and positively correlated with crispness; soluble solids and crude fiber were significantly and negatively related to vitamin C; crispness was significantly and positively correlated with crude fiber and vitamin C. Based on the above results, 4 representative indicators were used for evaluating fruit radish quality, that is water content, crispness, soluble solids, crude fiber, which could reflect the most information of fruit radish quality