Search

Abstract To date, earlier diagnosis of Alzheimer’s disease (AD) is still challenging. Recent studies revealed the elevated expression of connective tissue growth factor (CTGF) in AD brain is an upstream regulator of amyloid-beta (Aβ) plaque, thus CTGF could be an earlier diagnostic biomarker of AD than Aβ plaque. Herein, we develop a peptide-coated gold nanocluster that specifically targets CTGF with high affinity (KD ~ 21.9 nM). The probe can well penetrate the blood-brain-barrier (BBB) of APP/PS1 transgenic mice at early-stage (earlier than 3-month-old) in vivo, allowing non-invasive NIR-II imaging of CTGF when there is no appearance of Aβ plaque deposition. Notably, this probe can also be applied to measuring CTGF on postmortem brain sections by multimodal analysis, including fluorescence imaging, peroxidase-like chromogenic imaging, and ICP-MS quantitation, which enables distinguishment between the brains of AD patients and healthy people. This probe possesses great potential for precise diagnosis of earlier AD before Aβ plaque formation.

As the operating speed of electric multiple units (EMUs) in high-speed railways increases, pantograph–catenary (PC) detachment arcing occurs frequently. The resulting vehicular-grounding electromagnetic transients are related to the dynamic characteristics of the arc length. During large detachment, the processes of arc extinction and arc reignition may occur, resulting in more severe train body (TB) over-voltages and adverse effects on some vehicular electronic devices. As an extension of the previous works, this paper aims to establish a suitable PC arc model to examine the TB transient voltages. To begin with, the arc length dynamic characteristics are reasonably analyzed to deduce the relationship between the detachment distance and the arc length via the chain arc model. Then, the dynamic characteristics of the arc length are introduced, and an arc modeling scheme is proposed to elaborate the vehicle-grid electric power model for EMUs encountering various arcing scenarios. Based on this, the transient over-voltages are analyzed, accounting for both the arc extinction and arc reignition, as well as the mutual influences of multiple detachments in a short time. The influential factors, including arc length characteristics, phase angle, excitation inductance, and grounding parameters, are also involved in the performed analyses.

Peptide-protected gold nanoclusters (AuNCs), possessing exceptional biocompatibility and remarkable physicochemical properties, have demonstrated intrinsic pharmaceutical activity in immunomodulation, making them a highly attractive frontier in the field of nanomedicine exploration. Autoimmune hepatitis (AIH) is a serious autoimmune liver disease caused by the disruption of immune balance, for which effective treatment options are still lacking. In this study, we initially identified glutathione (GSH)-protected AuNCs as a promising nanodrug candidate for AIH alleviating in a Concanavalin A (Con A)-induced mice model. However, to enhance treatment efficiency, liver-targeted delivery needs to be improved. Therefore, human serum albumin (HSA)-encapsulated AuNCs were constructed to achieve enhanced liver targeting and more potent mitigation of Con A-induced elevations in plasma aspartate transaminase (AST), alanine transaminase (ALT), and liver injury in mice. In vivo and in vitro mechanism studies indicated that AuNCs could suppress the secretion of IFN-γ by Con A-stimulated T cells and subsequently inhibit the activation of the JAK2/STAT1 pathway and eventual hepatocyte apoptosis induced by IFN-γ. These actions ultimately protect the liver from immune cell infiltration and damage caused by Con A. These findings suggest that bio-protected AuNCs hold promise as nanodrugs for AIH therapy, with their liver targeting capabilities and therapeutic efficiency being further improved via rational surface ligand engineering.

Objective • Many randomized controlled trials (RCTs) have reported the effect of probiotics on reducing plasma lipids with inconsistent results. An explicit systematic review and meta-analysis were conducted in this study to evaluate the effect of probiotics on the lipid profile of healthy and hyperlipidemia participants. Methods • A comprehensive literature search of RCTs was conducted using PubMed, Embase, World Health Organization (WHO) Global Index Medicus, WHO clinical trial registry, and Clinicaltrials.gov. Inclusion criteria included RCTs comparing the use of any strain of a specified probiotic with the placebo control group. The change in lipid profiles was analyzed. Results • The probiotics can decrease the total cholesterol (TC) level in hyperlipidemia participants but not healthy persons (MD = -0.43, 95% CI -0.60 – -0.25, P < .01; MD = -0.09, 95% CI -0.26 – 0.08, P > .05). Probiotics did not reduce high-density lipoprotein cholesterol (HDL-C) in patients with hyperlipidemia or healthy people (MD = -0.01, 95% CI -0.09 – 0.07, P > .05; MD = 0.02, 95% CI -0.04 – 0.09, P > .05). Furthermore, probiotics can reduce the low-density lipoprotein cholesterol (LDL-C) level both in hyperlipidemia and healthy persons (MD = -0.34, 95% CI -0.43 – -0.26, P < .01; MD = -0.15, 95% CI -0.28 – -0.02, P < .05). Lastly, the effect of probiotics on reducing triglyceride (TG) levels was significant in hyperlipidemia persons but not in the healthy population (MD = -0.20, 95% CI -0.37 – -0.04, P < .01; MD = -0.01, 95% CI -0.02 – 0.04, P > .05). Conclusions • Through our analysis, the effect of probiotics on lowering plasma lipid was more obvious in hyperlipidemia participants than healthy population. However, further studies are required to confirm the findings due to pronounced clinical heterogeneity [ABSTRACT FROM AUTHOR]

Copper-based nanomaterials demonstrate promising potential in cancer therapy. Cu+ efficiently triggers a Fenton-like reaction and further consumes the high level of glutathione, initiating chemical dynamic therapy (CDT) and ferroptosis. Cuproptosis, a newly identified cell death modality that represents a great prospect in cancer therapy, is activated. However, active homeostatic systems rigorously keep copper levels within cells exceptionally low, which hinders the application of cooper nanomaterials-based therapy. Herein, a novel strategy of CRISPR-Cas9 RNP nanocarrier to deliver cuprous ions and suppress the expression of copper transporter protein ATP7A for maintaining a high level of copper in cytoplasmic fluid is developed. The Cu2O and organosilica shell would degrade under the high level of glutathione and weak acidic environment, further releasing RNP and Cu+. The liberated Cu+ triggered a Fenton-like reaction for CDT and partially transformed to Cu2+, consuming intracellular GSH and initiating cuproptosis and ferroptosis efficiently. Meanwhile, the release of RNP effectively reduced the expression of copper transporter ATP7A, subsequently increasing the accumulation of cooper and enhancing the efficacy of CDT, cuproptosis, and ferroptosis. Such tumor microenvironment responsive multimodal nanoplatform opens an ingenious avenue for colorectal cancer therapy based on gene editing enhanced synergistic cuproptosis/CDT/ferroptosis.

To investigate the impact of different seedling transplanting times on rice growth, the present study evaluated seedling age and root pruning using treatments consisting of root pruning (RC20, RC30, and RC40) and no root pruning (CK20, CK30, and CK40). Quantitative analysis using curve fitting of the changes in dry matter accumulation (DMA) during the seedling and field stages was performed, and the changes in root parameters during the re-greening stage were observed. The results showed that the seedling stage could be divided into a gradual increase period, a rapid increase period, and a slow increase period. Transplanting at different time periods resulted in different transplanting shock effects. During the field stage, the DMA exhibited a slow-fast-slow "S" shaped curve as the developmental time progressed. However, significant differences were observed in growth parameters among the different treatments. Root injury promoted early maturity in young seedlings but also prolonged the whole growth period in older seedlings. The inhibitory effect of root pruning on rice root growth increased with young seedling age. The present results provide a theoretical basis for the design of seedling needle structure and the optimisation of rice seedling cultivation practices.

Abstract Background Non‐apoptotic cell death is presently emerging as a potential direction to overcome the apoptosis resistance of cancer cells. In the current study, a natural plant agent α‐hederin (α‐hed) induces caspase‐independent paraptotic modes of cell death. Purpose The present study is aimed to investigate the role of α‐hed induces paraptosis and the associated mechanism of it. Methods The cell proliferation was detected by CCK‐8. The cytoplasm organelles were observed under electron microscope. Calcium (Ca2+) level was detected by flow cytometry. Swiss Target Prediction tool analyzed the potential molecule targets of α‐hed. Molecular docking methods were used to evaluate binding abilities of α‐hed with targets. The expressions of genes and proteins were analyzed by RT‐qPCR, western blotting, immunofluorescence, and immunohistochemistry. Xenograft models in nude mice were established to evaluate the anticancer effects in vivo. Results α‐hed exerted significant cytotoxicity against a panel of CRC cell lines by inhibiting proliferation. Besides, it induced cytoplasmic vacuolation in all CRC cells. Electron microscopy images showed the aberrant dilation of endoplasmic reticulum and mitochondria. Both mRNA and protein expressions of Alg‐2 interacting proteinX (Alix), the marker of paraptosis, were inhibited by α‐hed. Besides, both Swiss prediction and molecular docking showed that the structure of α‐hed could tightly target to GPCRs. GPCRs were reported to activate the phospholipase C (PLC)‐β3/ inositol 1,4,5‐trisphosphate receptor (IP3R)/ Ca2+/ protein kinase C alpha (PKCα) pathway, and we then found all proteins and mRNA expressions of PLCβ3, IP3R, and PKCα were increased by α‐hed. After blocking the GPCR signaling, α‐hed could not elevate Ca2+ level and showed less CRC cell cytotoxicity. MAPK cascade is the symbol of paraptosis, and we then demonstrated that α‐hed activated MAPK cascade by elevating Ca2+ flux. Since non‐apoptotic cell death is presently emerging as a potential direction to overcome chemo‐drug resistance, we then found α‐hed also induced paraptosis in 5‐fluorouracil‐resistant (5‐FU‐R) CRC cells, and it reduced the growth of 5‐FU‐R CRC xenografts. Conclusions Collectively, our findings proved α‐hed as a promising candidate for inducing non‐apoptotic cell death, paraptosis. It may overcome the resistance of apoptotic‐based chemo‐resistance in CRC.

Olfaction is critical for guiding the physiological activities of insects, with antennae being the primary olfactory organs. However, recent evidence suggests that other tissues may also participate in olfactory recognition. Among these, the genitalia of moths have received attention due to their roles in mating and oviposition. Sensilla and odorant receptors (ORs) in moth genitalia highlight the potential olfactory function of these structures. In this study, we examined the olfactory sensing capacity of the genitalia in Helicoverpa armigera by analyzing their structure in males and females and characterizing the expressed ORs. Scanning electron microscopy uncovered many sensilla distributed throughout the male and female genitalia. Transcriptome sequencing identified 20 ORs in the genitalia, with HarmOR68 exhibiting significant responses to methyl esters: methyl benzoate and salicylate. Our findings provide theoretical evidence that H. armigera genitalia may have significant olfactory perception functions.