PiR-hsa-23533 promotes malignancy in head and neck squamous cell carcinoma via USP7.

BACKGROUND: With regard to head and neck squamous cell carcinoma (HNSCC), its occurrence and advancement are controlled by genetic and epigenetic anomalies. PIWI-interacting RNAs (piRNAs) are recognized with significance in tumor, but the precise molecular mechanisms of piRNAs in HNSCC largely remain undisclosed. METHODS: Differentially expressed piRNAs were identified by RNA sequencing. The expression of piR-hsa-23533 was evaluated using quantitative real-time PCR and RNA in situ hybridization. The impacts of piR-hsa-23533 on the proliferation and apoptosis of HNSCC cells were investigated by a series of in vitro and in vivo assays. RESULTS: piR-hsa-23533 exhibits upregulation within HNSCC cells and tissues. Besides, piR-hsa-23533 overexpression promotes proliferation while inhibiting apoptosis in vitro and in vivo, while piR-hsa-23533 silencing has an opposite function. From the mechanistic perspective, piR-hsa-23533 can bind to Ubiquitin-specific protease 7 (USP7), as shown through RNA pull-down and RNA immunoprecipitation assays, promoting USP7 mRNA and protein expression. CONCLUSIONS: These findings highlight the functional importance of piR-hsa-23533 in HNSCC and may assist in the development of anti-HNSCC therapeutic target.

Microstructures of layered Ni-rich cathodes for lithium-ion batteries.

Millions of electric vehicles (EVs) on the road are powered by lithium-ion batteries (LIBs) based on nickel-rich layered oxide (NRLO) cathodes, and they suffer from a limited driving range and safety concerns. Increasing the Ni content is a key way to boost the energy densities of LIBs and alleviate the EV range anxiety, which are, however, compromised by the rapid performance fading. One unique challenge lies in the worsening of the microstructural stability with a rising Ni-content in the cathode. In this review, we focus on the latest advances in the understanding of NLRO microstructures, particularly the microstructural degradation mechanisms, state-of-the-art stabilization strategies, and advanced characterization methods. We first elaborate on the fundamental mechanisms underlying the microstructural failures of NRLOs, including anisotropic lattice evolution, microcracking, and surface degradation, as a result of which other degradation processes, such as electrolyte decomposition and transition metal dissolution, can be severely aggravated. Afterwards, we discuss representative stabilization strategies, including the surface treatment and construction of radial concentration gradients in polycrystalline secondary particles, the fabrication of rod-shaped primary particles, and the development of single-crystal NRLO cathodes. We then introduce emerging microstructural characterization techniques, especially for identification of the particle orientation, dynamic changes, and elemental distributions in NRLO microstructures. Finally, we provide perspectives on the remaining challenges and opportunities for the development of stable NRLO cathodes for the zero-carbon future.

Building Stable Anodes for High-Rate Na-Metal Batteries.

Due to low cost and high energy density, sodium metal batteries (SMBs) have attracted growing interest, with great potential to power future electric vehicles (EVs) and mobile electronics, which require rapid charge/discharge capability. However, the development of high-rate SMBs has been impeded by the sluggish Na+ ion kinetics, particularly at the sodium metal anode (SMA). The high-rate operation severely threatens the SMA stability, due to the unstable solid-electrolyte interface (SEI), the Na dendrite growth, and large volume changes during Na plating-stripping cycles, leading to rapid electrochemical performance degradations. This review surveys key challenges faced by high-rate SMAs, and highlights representative stabilization strategies, including the general modification of SMB components (including the host, Na metal surface, electrolyte, separator, and cathode), and emerging solutions with the development of solid-state SMBs and liquid metal anodes; the working principle, performance, and application of these strategies are elaborated, to reduce the Na nucleation energy barriers and promote Na+ ion transfer kinetics for stable high-rate Na metal anodes. This review will inspire further efforts to stabilize SMAs and other metal (e.g., Li, K, Mg, Zn) anodes, promoting high-rate applications of high-energy metal batteries towards a more sustainable society.

Interface Engineering Enables Wide-Temperature Li-Ion Storage in Commercial Silicon-Based Anodes.

Silicon-based materials have been considered potential anode materials for next-generation lithium-ion batteries based on their high theoretical capacity and low working voltage. However, side reactions at the Si/electrolyte interface bring annoying issues like low Coulombic efficiency, sluggish ionic transport, and inferior temperature compatibility. In this work, the surface Al2 O3 coating layer is proposed as an artificial solid electrolyte interphase (SEI), which can serve as a physical barrier against the invasion of byproducts like HF(Hydrogen Fluoride) from the decomposition of electrolyte, and acts as a fast Li-ion transport pathway. Besides, the intrinsically high mechanical strength can effectively inhibit the volume expansion of the silicon particles, thus promoting the cyclability. The as-assembled battery cell with the Al2 O3 -coated Si-C anode exhibits a high initial Coulombic efficiency of 80% at RT and a capacity retention ratio up to ≈81.9% after 100 cycles, which is much higher than that of the pristine Si-C anode (≈74.8%). Besides, the expansion rate can also be decreased from 103% to 50%. Moreover, the Al2 O3 -coated Si-C anode also extends the working temperature from room temperature to 0 °C-60 °C. Overall, this work provides an efficient strategy for regulating the interface reactions of Si-based anode and pushes forward the practical applications at real conditions.

Dietary Nucleotides Promote Neonatal Rat Microbiota-Gut-Brain Axis Development by Affecting Gut Microbiota Composition and Metabolic Function.

A variety of active factors in milk and foods have been proven to serve as microbial nutrients that regulate the formation of early gut microbiota (GM), thereby ensuring the healthy development of infants. This study demonstrated that dietary nucleotides (NTs), one of the main nitrogen-containing substances in human milk, promoted the neurodevelopment of neonatal rats and the expression of Sox2, Dcx, Tuj1, and NeuN in the prefrontal cortex and hippocampus, but had no significant regulatory effects in the striatum. 16s rRNA sequencing and metabolomics of the colon contents of neonatal rats at different developmental stages showed that the early intake of NTs promoted an increase in the abundance of beneficial microorganisms related to neurodevelopment, digestion, and gut absorption, such as g_Romboutsia and g_Akkermansia. Changes in the ability of the GM to regulate folate synthesis, riboflavin metabolism, and other processes were also observed. Further analysis revealed significant correlations between the level of characteristic metabolites, namely, trans-3-indoleacrylic acid, urocanic acid, inosine, and adenosine, in the gut with neurodevelopment and characteristic GM components. These findings suggest that NTs in milk may affect neurodevelopment and maturation in early life by regulating the GM composition-gut-brain axis.

Combined signature of N7-methylguanosine regulators with their related genes and the tumor microenvironment: a prognostic and therapeutic biomarker for breast cancer.

Background: Identifying predictive markers for breast cancer (BC) prognosis and immunotherapeutic responses remains challenging. Recent findings indicate that N7-methylguanosine (m7G) modification and the tumor microenvironment (TME) are critical for BC tumorigenesis and metastasis, suggesting that integrating m7G modifications and TME cell characteristics could improve the predictive accuracy for prognosis and immunotherapeutic responses. Methods: We utilized bulk RNA-sequencing data from The Cancer Genome Atlas Breast Cancer Cohort and the GSE42568 and GSE146558 datasets to identify BC-specific m7G-modification regulators and associated genes. We used multiple m7G databases and RNA interference to validate the relationships between BC-specific m7G-modification regulators (METTL1 and WDR4) and related genes. Single-cell RNA-sequencing data from GSE176078 confirmed the association between m7G modifications and TME cells. We constructed an m7G-TME classifier, validated the results using an independent BC cohort (GSE20685; n = 327), investigated the clinical significance of BC-specific m7G-modifying regulators by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, and performed tissue-microarray assays on 192 BC samples. Results: Immunohistochemistry and RT-qPCR results indicated that METTL1 and WDR4 overexpression in BC correlated with poor patient prognosis. Moreover, single-cell analysis revealed relationships between m7G modification and TME cells, indicating their potential as indicators of BC prognosis and treatment responses. The m7G-TME classifier enabled patient subgrouping and revealed significantly better survival and treatment responses in the m7Glow+TMEhigh group. Significant differences in tumor biological functions and immunophenotypes occurred among the different subgroups. Conclusions: The m7G-TME classifier offers a promising tool for predicting prognosis and immunotherapeutic responses in BC, which could support personalized therapeutic strategies.

Neuroprotective effect of chitosan oligosaccharide on alcohol-induced hippocampal injury using proteomic analysis.

Alcoholism is a serious public health problem, and the abuse of drinking seriously damages the health of people. Chitosan oligosaccharides (COSs) are small-molecule oligosaccharides with amino groups that have many unique properties. The neuroprotective effect of COS on alcohol-induced hippocampal injury in Sprague-Dawley (SD) rats was investigated. The discrimination ratio of the COS group in the Y-maze experiment was 59.3% higher than that of the ETOH group. Meanwhile, the discrimination index was less than 0 in the ETOH group but greater than 0 in the COS group during the object recognition test. The cells in the COS group were more tightly arranged than those in the ETOH group. Proteomics was used to identify differentially expressed proteins in the hippocampus. There were 27 differentially expressed proteins in the COS and ETOH group for further bioinformatic analysis. There are three enriched pathway categories, namely, primary immunodeficiency, hedgehog signaling, and sulfur relay system. Next, sonic hedgehog signaling pathway-related proteins were verified through western blotting. The protein expression level of ß-arrestin-2 in the COS group was 2.85 times higher than that in the ETOH group. This work may contribute to understanding the underlying mechanism of the neuroprotective effect of COS against alcohol-induced hippocampal injury in SD rats.

The efficacy and safety of telerehabilitation for patients following total knee arthroplasty: a overviews of systematic reviews.

BACKGROUND: Studies evaluating the effectiveness and safety of telerehabilitation in patients undergoing total knee arthroplasty (TKA) have increased. However, the study quality and results differ, systematic reviews are limited. We aimed to synthesise systematic reviews and meta-analyses to assess the effects of telerehabilitation in patients post-TKA. MATERIALS AND METHODS: Systematic reviews and meta-analyses regarding the effectiveness and safety of TKA telerehabilitation were retrieved from eight databases from establishment to 18 December 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), Risk of Bias in Systematic Reviews (ROBIS) and GRADE system were used to evaluate results, methods, bias and evidence quality. RESULTS: Thirteen systematic reviews and meta-analyses were analysed. The AMSTAR 2 showed low methodological quality in seven studies and very low quality in six. Among the key items, item 2 had been registered on website before systematic review in four reviews. Concerning item 4, did not provide a comprehensive search strategy in 4 reviews. For item 7, none of the reviews provided a list of reasons for excluding an article. For item 9, regarding whether appropriate tools were used to assess the risk of bias of each included study, one review was assessed as 'partially yes', one review only included RCTs, and the remainder were assessed as 'yes'. For item 11, one review did not specify the statistical methods used, and three reviews did not conduct a meta-analysis. For item 13, four reviews considered the risk of bias when interpreting or discussing the study results. For item 15, seven reviews did not evaluate publication bias. The PRISMA scores of the 13 reviews ranged from 17.5 to 26.0. The PRISMA indicated that 69.2% had no protocol registration, 38.5% did not provide other materials and evidence certainty, 23.1% did not provide certainty assessment, 30.8% did not report study bias. According to the ROBIS scale, diferrent domains have diferrent risks in all the reviews. CONCLUSION: Telerehabilitation positively affects walking ability, knee extension and patient costs post-TKA surgery. Regarding the quality of life, patient satisfaction and the WOMAC, telerehabilitation had similar effects to conventional rehabilitation. Owing to the low quality of the studies, these conclusions should be interpreted cautiously, high-quality studies are needed in the future.

Clinical study on single-port endoscopic resection via a gasless transaxillary approach in the treatment of breast fibroadenoma in adolescents.

BACKGROUND: Breast fibroadenoma is the most common benign breast tumour. This study aimed to investigate the advantages and disadvantages of endoscopic-assisted resection via a gas-less transaxillary single-port approach for breast fibroadenoma in adolescent patients, compared with a traditional approach. METHODS: The clinical data of 83 patients with breast fibroadenoma treated in our hospital from October 2019 to October 2021 were collected for retrospective analysis. These patients were divided into an endoscopic-assisted surgery (ES) group (n = 39) and a traditional open surgery (OS) group (n = 44) according to the surgical approach. The operative time, intraoperative blood loss, incision length, postoperative complications, and patient satisfaction were compared between the two groups. RESULTS: The surgical cost was (5.1 ± 0.6) thousand Yuan [(0.7 ± 0.1) thousand US dollars] in the ES group and (3.5 ± 2.7) thousand Yuan [(0.5 ± 0.4) thousand US dollars] in the OS group, showing a statistically significant difference (p < 0.001). There was no significant difference in surgical time, intraoperative blood loss, incision length, or the rate of postoperative complications between the two groups. Stratified analysis revealed that the ES group had a significantly shorter operative time [(57.00 ± 10.26) min vs. (78.27 ± 7.63)] (p < 0.001), a smaller incision length [(3.73 ± 0.34) cm vs. (4.42 ± 0.44) cm] (p < 0.001), and a lower complication incidence rate (11.1% vs. 63.6) (p = 0.011) than the OS group in the cases with a nodule number ≥ 3. The satisfaction score using the BREAST-Q scale indicated that psychosocial well-being and patient satisfaction with the breast in the ES group were significantly superior to those in the OS group [(91.18 ± 3.12) points vs. (87.00 ± 4.45) points and (91.03 ± 6.80) points vs. (84.45 ± 6.06) points, respectively] (p < 0.001). CONCLUSION: ES is a safe and effective method for the treatment of fibroadenoma. In patients with multiple fibroadenomas (≥ 3 tumours), ES has a shorter operative time and fewer postoperative complications. ES demonstrates a significant, prominent advantage in cosmetic appearance. However, it should be noted that ES is associated with higher costs than OS.

A Deep Learning Method for Rolling Bearing Fault Diagnosis Based on Attention Mechanism and Graham Angle Field.

Focusing on the low accuracy and timeliness of traditional fault diagnosis methods for rolling bearings which combine massive amounts of data, a fault diagnosis method for rolling bearings based on Gramian angular field (GAF) coding technology and an improved ResNet50 model is proposed. Using the Graham angle field technology to recode the one-dimensional vibration signal into a two-dimensional feature image, using the two-dimensional feature image as the input for the model, combined with the advantages of the ResNet algorithm in image feature extraction and classification recognition, we realized automatic feature extraction and fault diagnosis, and, finally, achieved the classification of different fault types. In order to verify the effectiveness of the method, the rolling bearing data of Casey Reserve University are selected for verification, and compared with other commonly used intelligent algorithms, the results show that the proposed method has a higher classification accuracy and better timeliness than other intelligent algorithms.

The E3 ubiquitin ligase MIB1 suppresses breast cancer cell migration through regulating CTNND1 protein level.

Breast cancer is one of the most common invasive cancers among women. The leading cause of difficulty in treating breast cancer patients is metastasis. Because cell migration is closely related to breast cancer metastasis, elucidating the detailed mechanism by which breast cancer cells promote their migration is crucial for improving the prognosis of patients. In this study, we investigated the relationship between breast cancer cell migration and Mind bomb1 (MIB1), an E3 ubiquitin ligase. We found that the downregulation of MIB1 promotes the cell migration of MCF7, a breast cancer-derived cell line. Furthermore, knockdown of MIB1 caused a reduction in CTNND1 and thereby impaired E-cadherin membrane localization in the cell boundary region. Taken together, our data suggest that MIB1 might play a role in suppressing breast cancer cell migration.

Differential reinforcement of intestinal barrier function by various Lactobacillus reuteri strains in mice with DSS-induced acute colitis.

AIMS: Inflammatory bowel disease is a complex, refractory disorder characterised by chronic gastrointestinal inflammation. Studies have reported that Lactobacillus reuteri alleviates gastrointestinal inflammation and strengthens the intestinal barrier. However, further biochemical and genetic studies are required to correctly understand the therapeutic potential of L. reuteri. MATERIALS AND METHODS: This study sought to further understand the anti-colitis effect of L. reuteri isolated from faecal samples of healthy locals by focusing on biochemical (immunological, mechanical, chemical and biological barriers) and genetic studies. KEY FINDINGS: In this study, we assessed and compared the benefits and efficacy of L. reuteri FYNDL13 and FCQHC8L in the treatment of colitis and found strain FYNDL13 to be superior to FCQHC8L in this regard. Compared with FCQHC8L, FYNDL13 was associated with more diverse and powerful regulatory pathways. Meanwhile, it encouraged butyric acid formation, upregulated antimicrobial peptide-coding gene transcription and prevented hyperimmune reactions on the intestinal periphery and within the intestine. Moreover, it enhanced the abundance of beneficial bacteria (Bifidobacterium, Akkermansia, Blautia and Oscillospira), thereby limiting the relative abundance of harmful bacteria (Bacteroides and Sutterella). Furthermore, the advantage might be attributed to metabolism- and defence system-related genomic characteristics. SIGNIFICANCE: Taken together, our study compares and summarizes a pathway paradigm of these two L. reuteri strains in reinforcing the intestinal barrier against colitis and identifies candidate genes responsible for microbiota-immune axis balance.

Ultrathin metal-organic framework nanosheets as building blocks of lamellar nanofilms for ultrafast molecular sieving.

Metal-organic framework (MOF) nanosheets have significant potential applications including separation, catalysis, and sensors. However, the on-demand design with tunable thickness and morphology remains a great challenge, leading to difficulties in modulating their hierarchical assembly for the preparation of macroscopic films. Herein, we report the successful synthesis of smooth and ultrathin MOF (Cu-TCPP (TCPP = 4,4,4,4-(porphine-5,10,15,20-tetrayl)tetrakis(benzoic acid))) nanosheets used in lamellar nanofilms for the rejection of organic molecules from water. Dopamine hydrochloride (DA-HCl) is used as an adjuvant in the synthesis. Facilitated by a HCl acid environment and DA competitive coordination, the normal and lateral growths of Cu-TCPP nanosheets are modulated to achieve the desired thickness and morphology. DA-HCl can be also easily removed from the nanosheets without affecting their physicochemical properties. The as-synthesized nanosheets are utilized as nanofilm building blocks in which they are stacked into ordered bricks. The obtained membrane displays an ultrahigh water permeance of 2540 L m-2 h-1 bar-1, which is two orders of magnitude higher than the currently reported polymer membranes, while it does not sacrifice the solute rejection as completely determined by the intrinsic pore size of the nanosheets (i.e., 98.8% for molecules larger than 1.3 nm). This work provides a novel and facile strategy to tailor the morphology of the MOF nanosheets for maximizing their functionalities and structure superiority in many engineering applications.

Physiological and molecular mechanisms of the response of roots of Pinus massoniana Lamb. to low-temperature stress.

Pinus massoniana Lamb. is the timber species with the widest distribution and the largest afforestation area in China, providing a large amount of timber, turpentine and ecological products. but low temperature limits its growth and geographical distribution. Physiological and molecular studies can well explain the mechanism of P. massoniana response to low temperature. In this study, physiological and biochemical indexes, cell morphology, lignin content, gene regulatory networks, and gene expression patterns of different P. massoniana varieties (cold-tolerant and cold-sensitive) were studied from physiological, biochemical, and molecular perspectives. The results indicated that under low-temperature stress, the cold-tolerant cultivar maintained high contents of osmoregulatory substances, and the root morphology and structure remained intact. In the initial stage of low-temperature stress, the number of differentially expressed genes was 7148, and with the extension of stress time, the number of differentially expressed genes decreased to 1991. P. massoniana might direct its responses to low temperature by regulating phenylpropane metabolism, starch and sucrose metabolism, hormone signaling pathways, and transcription factors. BAM, 4CL, CCoAOMT, PRX5, WRKYs, and hormone synthesis related genes play important roles. P. massoniana cultivars may vary in response mechanisms. In this study, physiological and analytical techniques were used to study the root tip response mechanism of Masson's pine to low temperature stress. The results of this study lay a foundation for in-depth research on the molecular functions of P. massoniana under low-temperature stress conditions.

Topological polarization singular lasing with highly efficient radiation channel.

Bound states in the continuum (BICs) in photonic crystals describe the originally leaky Bloch modes that can become bounded when their radiation fields carry topological polarization singularities. However, topological polarization singularities do not carry energy to far field, which limits radiation efficiencies of BICs for light emitting applications. Here, we demonstrate a topological polarization singular laser which has a topological polarization singular channel in the second Brillouin zone and a paired linearly polarized radiation channel in the first Brillouin zone. The presence of the singular channel enables the lasing mode with a higher quality factor than other modes for single mode lasing. In the meanwhile, the presence of the radiation channel secures the lasing mode with high radiation efficiency. The demonstrated topological polarization singular laser operates at room temperature with an external quantum efficiency exceeding 24%. Our work presents a new paradigm in eigenmode engineering for mode selection, exotic field manipulation and lasing.

Identification of WRKY transcription factor family genes in Pinus massoniana Lamb. and their expression patterns and functions in response to drought stress.

BACKGROUND: Pinus massoniana Lamb. is the timber species with the widest distribution and the largest afforestation area in China, providing a large amount of timber, turpentine and ecological products. Seasonal drought caused by climate warming severely constrains the quality and growth of P. massoniana forests. WRKY transcription factors play an important role in plant responses to abiotic stress. In this study, the molecular mechanisms by which P. massoniana responds to drought stress were analysed based on the P. massoniana WRKY (PmWRKY) family of genes. RESULTS: Forty-three PmWRKYs are divided into three major families, 7 sub-families, and the conserved motifs are essentially the same. Among these 43 PmWRKYs express under drought stress but with different expression patterns in response to stress. PmWRKYs respond to drought stress induced by exogenous hormones of SA, ABA, and MeJA. The expression of PmWRKY6, PmWRKY10, and PmWRKY30 up-regulate in different families and tissues under drought stress, while PmWRKY22 down-regulate. Transgenetic tobaccos of PmWRKY31 are with lower malondialdehyde (MDA) content and higher proline (Pro) content than wild type (WT) tobaccos. In transgenic tobaccos of PmWRKY31, expression levels of related genes significantly improve, and drought tolerance enhance. CONCLUSIONS: This study analysed the molecular biological characteristics of PmWRKYs and investigated the expression patterns and functions of PmWRKYs in response to drought stress in P. massoniana. The results of this study provide a basis for in-depth research of the molecular functions of PmWRKYs in response to drought stress.

Bifidobacterium adolescentis Is Effective in Relieving Type 2 Diabetes and May Be Related to Its Dominant Core Genome and Gut Microbiota Modulation Capacity.

The prevalence of diabetes mellitus is increasing globally. Probiotics have been shown to be an effective intervention for diabetes. This study focused on the relieving effects and possible mechanisms of 16 strains of two dominant Bifidobacterium species (B. bifidum and B. adolescentis, which exist in the human gut at different life stages) on type 2 diabetes (T2D). The results indicated that more B. adolescentis strains appeared to be superior in alleviating T2D symptoms than B. bifidum strains. This effect was closely related to the ability of B. adolescentis to restore the homeostasis of the gut microbiota, increase the abundance of short-chain fatty acid-producing flora, and alleviate inflammation in mice with T2D. In addition, compared with B. bifidum, B. adolescentis had a higher number of core genes, and these genes were more evolutionarily stable, including unique environmental tolerance, carbon and nitrogen utilization genes, and a blood sugar regulation gene, glgP. This may be one of the reasons why B. adolescentis is more likely to colonize in the adult gut and show a superior ability to relieve T2D. This study provides insights into future studies aimed at investigating probiotics for the treatment of metabolic diseases.

Chitosan oligosaccharides exert neuroprotective effects via modulating the PI3K/Akt/Bcl-2 pathway in a Parkinsonian model.

Parkinson's disease (PD), the second most common neurodegenerative disease, is a threat to patients due to the inability to prevent or decelerate disease progression. Currently, most clinical drugs for the treatment of PD are synthetic drugs that always present undesirable adverse or toxic effects. Chitosan oligosaccharide (COS) is a natural oligosaccharide that has been considered relatively safe and studied in the therapeutic effects on different types of neuronal disorders. In this study, we separated four COS monomers (COSs) including chitobiose (COS2), chitotriose (COS3), chitotetraose (COS4) and chitopentaose (COS5) to explore their structure-activity relationship in PD mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Techniques including TLC, HPLC, MS, and NMR were applied to investigate the purity and structure of the COSs. After the oral administration of COSs, behavior indexes, pathological indexes, cytokines, and expression of proteins in the nigrostriatal pathway of the mice were analyzed. The results showed that the four COSs were fully deacetylated and the purity was >90%. Additionally, the neurobehavioral deficits of the PD mice were improved by treatment with COSs. The results further proved that COSs could protect the TH-labelled dopaminergic neurons via reducing the overexpression of α-synuclein, alleviating neuroinflammation, and activating the PI3K/Akt/Bcl-2 pathway to reduce apoptosis. COS3 exhibited a better effect on protecting dopaminergic neurons; however, COS2 provided a better effect on reducing the overexpression of α-synuclein. To conclude, the neuroprotective activity makes COSs a viable candidate as an ingredient for healthcare products.

Toxic Effects and Mechanisms of Silver and Zinc Oxide Nanoparticles on Zebrafish Embryos in Aquatic Ecosystems.

The global application of engineered nanomaterials and nanoparticles (ENPs) in commercial products, industry, and medical fields has raised some concerns about their safety. These nanoparticles may gain access into rivers and marine environments through industrial or household wastewater discharge and thereby affect the ecosystem. In this study, we investigated the effects of silver nanoparticles (AgNPs) and zinc oxide nanoparticles (ZnONPs) on zebrafish embryos in aquatic environments. We aimed to characterize the AgNP and ZnONP aggregates in natural waters, such as lakes, reservoirs, and rivers, and to determine whether they are toxic to developing zebrafish embryos. Different toxic effects and mechanisms were investigated by measuring the survival rate, hatching rate, body length, reactive oxidative stress (ROS) level, apoptosis, and autophagy. Spiking AgNPs or ZnONPs into natural water samples led to significant acute toxicity to zebrafish embryos, whereas the level of acute toxicity was relatively low when compared to Milli-Q (MQ) water, indicating the interaction and transformation of AgNPs or ZnONPs with complex components in a water environment that led to reduced toxicity. ZnONPs, but not AgNPs, triggered a significant delay of embryo hatching. Zebrafish embryos exposed to filtered natural water spiked with AgNPs or ZnONPs exhibited increased ROS levels, apoptosis, and lysosomal activity, an indicator of autophagy. Since autophagy is considered as an early indicator of ENP interactions with cells and has been recognized as an important mechanism of ENP-induced toxicity, developing a transgenic zebrafish system to detect ENP-induced autophagy may be an ideal strategy for predicting possible ecotoxicity that can be applied in the future for the risk assessment of ENPs.

IGF-1R/YAP signaling pathway is involved in collagen V-induced insulin biosynthesis and secretion in rat islet INS-1 cells.

PURPOSE: Type V collagen (collagen V) is one of the important components of extracellular matrix (ECM) in pancreas. We previously reported that pre-coating collagen V on the culture dishes enhanced insulin production in INS-1 rat pancreatic ß cells. In this study, we investigate the underlying mechanism. RESULTS: Insulin biosynthesis and secretion are both increased in INS-1 cells cultured on collagen V-coated dishes, accompanied by the reduced nuclear translocation of Yes-associated protein (YAP), a transcriptional co-activator. YAP, the downstream effector of Hippo signaling pathway, plays an important role in the development and function of pancreas. Inhibition of YAP activation by verteporfin further up-regulates insulin biosynthesis and secretion. Silencing large tumor suppressor (LATS), a core component of Hippo pathway which inhibits activity of YAP by phosphorylation, by siRNA transfection inhibits both insulin biosynthesis and secretion. In the present study, the protein level of insulin-like growth factor 1 receptor (IGF-1 R), detected as the upstream molecule of YAP, is reduced in the INS-1 cells cultured on the dishes coated with collagen V. The silencing of IGF-1 R by siRNA transfection further enhances insulin biosynthesis and secretion. IGF-1 treatment reduces collagen V-induced up-regulation of insulin biosynthesis and secretion, accompanying the increased nuclear YAP. CONCLUSION: Inhibition of IGF-1 R/YAP signal pathway is involved in collagen V-induced insulin biosynthesis and secretion in INS-1 cells.