Stage-specific requirement for METTL3-dependent m6A modification during dental pulp stem cell differentiation.

BACKGROUND: N6-methyladenosine (m6A) is the most prevalent epigenetic modification in eukaryotic messenger RNAs and plays a critical role in cell fate transition. However, it remains to be elucidated how m6A marks functionally impact the transcriptional cascades that orchestrate stem cell differentiation. The present study focuses on the biological function and mechanism of m6A methylation in dental pulp stem cell (DPSC) differentiation. METHODS: m6A RNA immunoprecipitation sequencing was utilized to assess the m6A-mRNA landscape during DPSC differentiation. Ectopic transplantation of DPSCs in immunodeficient mice was conducted to verify the in vitro findings. RNA sequencing and m6A RNA immunoprecipitation sequencing were combined to identify the candidate targets. RNA immunoprecipitation and RNA/protein stability of Noggin (NOG) were evaluated. The alteration in poly(A) tail was measured by 3'-RACE and poly(A) tail length assays. RESULTS: We characterized a dynamic m6A-mRNA landscape during DPSC mineralization with increasing enrichment in the 3' untranslated region (UTR). Methyltransferase-like 3 (METTL3) was identified as the key m6A player, and METTL3 knockdown disrupted functional DPSC differentiation. Moreover, METTL3 overexpression enhanced DPSC mineralization. Increasing m6A deposition in the 3' UTR restricted NOG expression, which is required for DPSC mineralization. This stage-specific m6A methylation and destabilization of NOG was suppressed by METTL3 knockdown only in differentiated DPSCs. Furthermore, METTL3 promotes the degradation of m6A-tagged NOG by shortening the poly(A) tail length in the differentiated stage. CONCLUSIONS: Our results address an essential role of dynamic m6A signaling in the temporal control of DPSC differentiation and provide new insight into epitranscriptomic mechanisms in stem cell-based therapy.

Graphene-based nanomaterials for breast cancer treatment: promising therapeutic strategies.

Breast cancer is the most common malignancy in women, and its incidence increases annually. Traditional therapies have several side effects, leading to the urgent need to explore new smart drug-delivery systems and find new therapeutic strategies. Graphene-based nanomaterials (GBNs) are potential drug carriers due to their target selectivity, easy functionalization, chemosensitization and high drug-loading capacity. Previous studies have revealed that GBNs play an important role in fighting breast cancer. Here, we have summarized the superior properties of GBNs and modifications to shape GBNs for improved function. Then, we focus on the applications of GBNs in breast cancer treatment, including drug delivery, gene therapy, phototherapy, and magnetothermal therapy (MTT), and as a platform to combine multiple therapies. Their advantages in enhancing therapeutic effects, reducing the toxicity of chemotherapeutic drugs, overcoming multidrug resistance (MDR) and inhibiting tumor metastasis are highlighted. This review aims to help evaluate GBNs as therapeutic strategies and provide additional novel ideas for their application in breast cancer therapy.

Nanomaterial-mediated autophagy: coexisting hazard and health benefits in biomedicine.

BACKGROUND: Widespread biomedical applications of nanomaterials (NMs) bring about increased human exposure risk due to their unique physicochemical properties. Autophagy, which is of great importance for regulating the physiological or pathological activities of the body, has been reported to play a key role in NM-driven biological effects both in vivo and in vitro. The coexisting hazard and health benefits of NM-mediated autophagy in biomedicine are nonnegligible and require our particular concerns. MAIN BODY: We collected research on the toxic effects related to NM-mediated autophagy both in vivo and in vitro. Generally, NMs can be delivered into animal models through different administration routes, or internalized by cells through different uptake pathways, exerting varying degrees of damage in tissues, organs, cells, and organelles, eventually being deposited in or excreted from the body. In addition, other biological effects of NMs, such as oxidative stress, inflammation, necroptosis, pyroptosis, and ferroptosis, have been associated with autophagy and cooperate to regulate body activities. We therefore highlight that NM-mediated autophagy serves as a double-edged sword, which could be utilized in the treatment of certain diseases related to autophagy dysfunction, such as cancer, neurodegenerative disease, and cardiovascular disease. Challenges and suggestions for further investigations of NM-mediated autophagy are proposed with the purpose to improve their biosafety evaluation and facilitate their wide application. Databases such as PubMed and Web of Science were utilized to search for relevant literature, which included all published, Epub ahead of print, in-process, and non-indexed citations. CONCLUSION: In this review, we focus on the dual effect of NM-mediated autophagy in the biomedical field. It has become a trend to use the benefits of NM-mediated autophagy to treat clinical diseases such as cancer and neurodegenerative diseases. Understanding the regulatory mechanism of NM-mediated autophagy in biomedicine is also helpful for reducing the toxic effects of NMs as much as possible.

Insights into the angiogenic effects of nanomaterials: mechanisms involved and potential applications.

The vascular system, which transports oxygen and nutrients, plays an important role in wound healing, cardiovascular disease treatment and bone tissue engineering. Angiogenesis is a complex and delicate regulatory process. Vascular cells, the extracellular matrix (ECM) and angiogenic factors are indispensable in the promotion of lumen formation and vascular maturation to support blood flow. However, the addition of growth factors or proteins involved in proangiogenic effects is not effective for regulating angiogenesis in different microenvironments. The construction of biomaterial scaffolds to achieve optimal growth conditions and earlier vascularization is undoubtedly one of the most important considerations and major challenges among engineering strategies. Nanomaterials have attracted much attention in biomedical applications due to their structure and unique photoelectric and catalytic properties. Nanomaterials not only serve as carriers that effectively deliver factors such as angiogenesis-related proteins and mRNA but also simulate the nano-topological structure of the primary ECM of blood vessels and stimulate the gene expression of angiogenic effects facilitating angiogenesis. Therefore, the introduction of nanomaterials to promote angiogenesis is a great helpful to the success of tissue regeneration and some ischaemic diseases. This review focuses on the angiogenic effects of nanoscaffolds in different types of tissue regeneration and discusses the influencing factors as well as possible related mechanisms of nanomaterials in endothelial neovascularization. It contributes novel insights into the design and development of novel nanomaterials for vascularization and therapeutic applications.

Key Role of Microtubule and Its Acetylation in a Zinc Oxide Nanoparticle-Mediated Lysosome-Autophagy System.

Autophagy is a biological process that has attracted considerable attention as a target for novel therapeutics. Recently, nanomaterials (NMs) have been reported to modulate autophagy, which makes them potential agents for the treatment of autophagy-related diseases. In this study, zinc oxide nanoparticles (ZNPs) are utilized to evaluate NM-induced autophagy and debate the mechanisms involved. It is found that ZNPs undergo pH-dependent ion shedding and that intracellular zinc ions (Zn2+ ) play a crucial role in autophagy. Autophagy is activated with ZNPs treatment, which is inhibited after Zn2+ sequestration via ethylenediamine tetra-acetic acid. Lysosome-based autophagic degradation is halted after ZNPs treatment for more than 3 h and is accompanied by blockage of lysophagy, which renews impaired lysosomes. Furthermore, the microtubule (MT) system participates in ZNP-induced lysosome-autophagy system changes, especially in the fusion between autophagosomes and lysosomes. MT acetylation is helpful for protecting from ZNP-induced MT disruption, and it promotes the autophagic degradation process. In conclusion, this study provides valuable information on NM-induced lysosome-autophagy system changes, particularly with respect to the role of lysophagy and the MT system, which point to some attractive targets for the design of engineered nanoparticles.

Neuroinflammation is induced by tongue-instilled ZnO nanoparticles via the Ca2+-dependent NF-κB and MAPK pathways.

BACKGROUND: The extensive biological applications of zinc oxide nanoparticles (ZnO NPs) in stomatology have created serious concerns about their biotoxicity. In our previous study, ZnO NPs were confirmed to transfer to the central nervous system (CNS) via the taste nerve pathway and cause neurodegeneration after 30 days of tongue instillation. However, the potential adverse effects on the brain caused by tongue-instilled ZnO NPs are not fully known. METHODS: In this study, the biodistribution of Zn, cerebral histopathology and inflammatory responses were analysed after 30 days of ZnO NPs tongue instillation. Moreover, the molecular mechanisms underlying neuroinflammation in vivo were further elucidated by treating BV2 and PC12 cells with ZnO NPs in vitro. RESULTS: This analysis indicated that ZnO NPs can transfer into the CNS, activate glial cells and cause neuroinflammation after tongue instillation. Furthermore, exposure to ZnO NPs led to a reduction in cell viability and induction of inflammatory response and calcium influx in BV2 and PC12 cells. The mechanism underlying how ZnO NPs induce neuroinflammation via the Ca2+-dependent NF-κB, ERK and p38 activation pathways was verified at the cytological level. CONCLUSION: This study provided a new way how NPs, such as ZnO NPs, induce neuroinflammation via the taste nerve translocation pathway, a new mechanism for ZnO NPs-induced neuroinflammation and a new direction for nanomaterial toxicity analysis.

CD44 and CD44v6 are Correlated with Gastric Cancer Progression and Poor Patient Prognosis: Evidence from 42 Studies.

BACKGROUND/AIMS: The prognostic power of the levels of total CD44 and its isoform CD44v6 for patients with gastric cancer (GC) remains controversial. Therefore, our study aims to generalize the clinicopathological and prognostic significance of these two proteins in GC. METHODS: A literature search of the PubMed, Web of Science and Embase databases was conducted to identify eligible studies. The odds ratio (OR) with a 95% confidence interval (CI) was used to assess the effects. RESULTS: In all, 42 studies including 6,229 patients were included in this analysis. Total CD44 was mentioned in 21 papers, and the results showed that CD44 was positively correlated with the T category, the N category, distant metastasis, lymphatic invasion and TNM stage. Moreover, patients with CD44 overexpression had a lower 5-year overall survival (OS) rate (OR = 3.35, 95%CI = 1.83-6.13). CD44v6 was mentioned in 24 studies, with results that were similar to those for total CD44. However, total CD44 or CD44v6 expression was not correlated with tumor size and histological grade. CONCLUSION: High CD44 or CD44v6 expression levels were correlated with cancer progression and poor prognosis in patients with GC. Both CD44 and CD44v6 may be useful diagnostic or prognostic biomarkers for GC.

DNA repair gene XRCC3 polymorphisms and bladder cancer risk: a meta-analysis.

The X-ray repair cross-complementing group 3 (XRCC3) in homologous recombination repair (HRR) pathway plays a vital role in DNA double-strand break repair (DSBR). Variants in the XRCC3 gene might result in altered protein structure or function which may influence DSBR efficiency and lead to cancer. Numerous epidemiological studies have been conducted to evaluate the association between XRCC3 polymorphisms and bladder cancer risk. However, the results of these previous studies have been inconsistent. To derive a more precise estimation of the association, we performed a meta-analysis of all available studies relating XRCC3 polymorphisms and bladder cancer. All studies published up to April 2013 on the association between XRCC3 polymorphisms and bladder cancer risk were identified by searching electronic databases PubMed, EMBASE, and Chinese Biomedical Literature databases. The association between the XRCC3 polymorphisms and bladder cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). A total of 16 case-control studies met the inclusion criteria and were selected. With respect to C18067T polymorphism, significant increased bladder cancer risk was found when all eligible studies were pooled into the meta-analysis (TT vs. CC: OR = 1.174, 95%CI = 1.033-1.335, P = 0.014 and recessive model TT vs. TC + CC: OR = 1.147, 95%CI = 1.020-1.290, P = 0.022, respectively). The results were still significant after excluding the Hardy-Weinberg equilibrium violation studies (TT vs. CC: OR = 1.178, 95%CI = 1.036-1.339, P = 0.013 and recessive model TT vs. TC + CC: OR = 1.144, 95%CI = 1.017-1.287, P = 0.025, respectively). In subgroup analysis by ethnicity, significant elevated risk was found among Asians (dominant model TT + TC vs. CC: OR = 1.285, 95%CI = 1.012-1.631). In the subgroup analyses according to smoking status, no significant association was detected in all genetic comparison models. With respect to A17893G and A4541G polymorphisms, no significant association with bladder cancer risk was observed in the overall and subgroup analyses. This meta-analysis suggests that the XRCC3 C18067T polymorphism was associated with increased bladder cancer risk especially among Asians. However, the XRCC3 A17893G and A4541G polymorphisms may not play important roles in bladder carcinogenesis. Further studies with larger sample sizes are needed to validate our finds.

Meta-analysis: eating frequency and risk of colorectal cancer.

Eating frequency has been implicated in the risk of colorectal cancer (CRC) in several epidemiological studies with contradictory and inconclusive findings. We performed a meta-analysis to evaluate their relationship. The pooled relative risk (RR) with 95% confidence interval (CI) was calculated to estimate the effects. A total of 15 eligible studies with 141,431 subjects and 11,248 cases were retrieved after a comprehensive search of the PubMed, Cochrane Library, and Web of Science databases up to October 2013. The overall meta-analysis revealed no strong significant association between eating frequency and risk of CRC in different eating occasion categories (1 meal/day): RR = 1.01, 95% CI 0.94-1.09, P = 0.709; 3 vs. <3 daily meals: RR = 1.17, 95% CI 0.93-1.46; 4 vs. <3 daily meals: RR = 1.13, 95% CI 0.92-1.38; ≥ 5 vs. <3 daily meals: RR = 0.95, 95% CI 0.61-1.47; 4 vs. ≤ 3 daily meals: RR = 1.18, 95% CI 0.92-1.51; and 1-2 vs. 3 or 4 daily meals: RR = 0.82, 95% CI 0.63-1.06). However, modest evidence of an increased risk of CRC in case-control studies (RR = 1.30; 95% CI, 1.11-1.52) and ≥ 5 vs. ≤ 3 meals group (RR = 1.30; 95% CI, 1.11-1.52) was observed. Our meta-analysis results do not support the hypothesis that eating frequency strongly reduced or increased the risk of CRC. Clinical randomized trials are required to evaluate this relationship further.

The association of interleukin-16 gene polymorphisms with IL-16 serum levels and risk of nasopharyngeal carcinoma in a Chinese population.

Interleukin (IL)-16 plays a fundamental role in inflammatory diseases, as well as in the development and progression of tumors. Genetic variation in DNA sequence of IL16 gene may lead to altered cytokine production and/or activity, and this variation may modulate an individual's susceptibility to nasopharyngeal carcinoma (NPC). To test this hypothesis, we investigated the association of IL16 gene polymorphisms and serum IL-16 levels with NPC risk in a Chinese population. We analyzed IL16 gene rs11556218 T/G, rs4778889 T/C, and rs4072111 C/T polymorphisms using PCR-RFLP and DNA sequencing, and serum IL-16 levels were measured by ELISA. The IL16 rs11556218 T/G polymorphism was significantly associated with the susceptibility to NPC patients. The TG genotype was associated with a significantly higher risk of NPC as compared with the TT genotype (OR = 2.05, 95% CI 1.04-4.01; p = 0.037). Patients carrying the G allele had a significantly higher risk for developing NPC compared with individuals carrying the T allele (OR = 1.79, 95% CI 1.07-3.01; p = 0.027). The serum IL-16 levels were increased in NPC patients compared with controls (p < 0.01); the genotypes carrying the IL16 rs11556218 G variant allele were associated with increased serum IL-16 levels compared with the homozygous wild-type genotype in NPC patients (all p values <0.01). Our data suggested that IL16 rs11556218 T/G polymorphism was associated with increased susceptibility to NPC through increasing the production of serum IL-16 levels.

S-1-based therapy versus S-1 monotherapy in advanced gastric cancer: a meta-analysis.

This study aimed to derive a more precise estimate of the prognostic significance of S-1-based therapy over S-1 monotherapy in patients with advanced gastric cancer (AGC), including overall survival (OS) time, progression-free survival (PFS) time, objective response rate (ORR), and adverse events (AEs). Studies stratifying OS, PFS, ORR, and AEs in AGC patients in an S-1-based therapy versus an S-1 monotherapy setting were eligible for analysis by systematic computerized PubMed, Embase and Cochrane Library searches. Data from these studies were pooled using STATA package version 11.0. Six studies that investigated outcomes in a total of 913 AGC cases, of which 443 (48.5%) received S-1-based therapy and 470 (51.5%) received S-1 monotherapy, were included in the meta-analysis. Median OS and median PFS were significantly prolonged in AGC patients receiving S-1-based therapy compared with those receiving S-1 monotherapy (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.71-0.96, P = 0.015, and HR 0.69, 95% CI 0.60-0.80, P = 0.000, respectively). The ORR favored patients with S-1-based therapy (OR 1.65, 95% CI 1.34-2.06, P = 0.000). Higher incidence of grade 3/4 neutropenia was found in patients with S-1-based therapy (P = 0.000). For the Asian population, S-1-based therapy significantly improved OS and PFS and enhanced ORR in comparison to S-1 monotherapy. The safety profile was poorer in patients with S-1-based therapy, but could be considerable between the S-1-based therapy and S-1 monotherapy group. Our conclusion needs to be confirmed via high-quality trials and the results need to be reproduced in other regions and populations.

ERCC1 expression levels predict the outcome of platinum-based chemotherapies in advanced bladder cancer: a meta-analysis.

The objective of this study was to provide a precise evaluation of whether expression levels of excision repair cross-complementation group 1 (ERCC1) are associated with objective response, overall survival (OS), and median survival in patients with advanced bladder cancer treated with platinum-based chemotherapy. Systematic computerized searches of the electronic databases PubMed, EMBASE, Ovid, ASCO, and CNKI were performed and a meta-analysis was carried out to evaluate the correlation between ERCC1 expression levels and objective response rate, OS, or progression-free survival in patients with advanced bladder cancer receiving platinum-based chemotherapy. References within the articles identified were also searched manually. STATA package version 11.0 was used for the comprehensive quantitative analyses. A total of six studies involving 356 patients, of which ERCC1 expression was high/positive in 138 (38.8%) and low/negative in 218 (61.2%), were included in the meta-analysis. The median age of the patients was 63.7 years. The objective response rate favored patients with ERCC1 low/negative expression after platinum-based chemotherapy, but showed no significant difference [odds ratio 0.86, 95% confidence interval (CI) 0.36-2.06, P=0.734]. The median OS time and the median progression-free survival time were significantly prolonged when ERCC1 low/negative expression was compared with ERCC1 high/positive expression (hazard ratio 0.69, 95% CI 0.54-0.89, P=0.004, and hazard ratio 0.76, 95% CI 0.66-0.89, P=0.000, respectively). In conclusion, low/negative expression of ERCC1 was associated with higher objective response, median progression-free survival, and median OS in patients with advanced bladder cancer treated with platinum-based chemotherapy. ERCC1 may be a suitable marker of prognosis and sensitivity to platinum-based chemotherapy in patients with advanced bladder cancer. Larger studies and further clinical trials are warranted to confirm these findings.

Establishing reference values for blood urea nitrogen and serum creatinine in Chinese Han ethnic adult men.

BACKGROUND: The aim was to calculate the two-sided 95th percentile reference values for blood urea nitrogen (BUN) and serum creatinine (SCr) in Chinese Han ethnic adult men. METHODS: Serum samples were collected from Chinese Han ethnic adult men aged 20 - 69 years. After screening based on the inclusion and exclusion criteria, a total of 1575 individuals were enrolled in our study. BUN and SCr values were measured on an automatic analyzer (Dade Behring, USA). The data was analyzed and calculated using nonparametric statistical methods. RESULTS: BUN and SCr values were not normally distributed. The reference values were in the range 3.3 - 7.5 mmol/L for BUN and 64 - 113 micromol/L for SCr. BUN levels were significantly lower in the smoking group than the non-smoking group (Z = -4.52, p < 10(-5)). An increase with age was observed in BUN levels (r(s) = 0.172, p < 0(-5)) and lower SCr levels were weakly associated with the older subjects (r(s) = -0.071, p = 0.005). Moreover, it was found that higher Body Mass Index (BMI) tended toward higher levels of SCr (r(s) = 0.118, p < 10(-5)). CONCLUSIONS: The reference values established for BUN and SCr exhibit a slight deviation compared to those developed in previous studies. We propose reference values of BUN for smokers and non-smokers be constructed, and age- and BMI-specific reference values be applied in clinical laboratories.

Determination of reference intervals for serum complement C3 and C4 levels in Chinese Han ethnic males.

BACKGROUND: Clinical laboratory reference intervals (RIs) for serum complement C3 and C4 levels have been established in many countries but there is a lack of published data regarding normal RIs in Chinese population. We attempted to establish RIs for serum complement C3 and C4 levels in Chinese Han ethnic males. METHODS: A total of 1,234 healthy male subjects, aged 20 - 69 years, were collected from the Fangchenggang Area Male Health and Examination Survey (FAMHES). Serum complement C3 and C4 levels were measured by immunoturbidimetry. The two-sided 95-percentile RIs were calculated using parametric statistical methods. RESULTS: Serum C3 values showed normal distribution and C4 were log-normal distributed. The two-sided 95% RIs (mean +/- 2 SD) for serum C3 and C4 were 0.656 - 1.52 g/L and 0.181 - 0.561 g/L, respectively. Body Mass Index (BMI) had a significant positive association with C3 (r = 0.342) and C4 (r = 0.258), and age had a significant positive association with C4 (r = 0.117). No significant difference was found either between smoking groups or drinking groups. A significant increase with BMI was found both for C3 (p < 0.001) and C4 (p < 0.001). BMI-specific RIs were also calculated. CONCLUSIONS: The RIs for serum C3 and C4 show a slight deviation compared to previously reported reference levels. BMI-specific reference values should be implemented in clinical laboratories.

Inverted loading strategy regulates the Mn-OV-Ce sites for efficient fenton-like catalysis.

Regulating interfacial active sites to improve peroxymonosulfate (PMS) activation efficiency is a hot topic in the heterogeneous catalysis field. In this study, we develop an inverted loading strategy to engineer asymmetric Mn-OV-Ce sites for PMS activation. Mn3O4@CeO2 prepared by loading CeO2 nanoparticles onto Mn3O4 nanorods exhibits the highest catalytic activity and stability, which is due to the formation of more oxygen vacancies (OV) at the Mn-OV-Ce sites, and the surface CeO2 layer effectively inhibits corrosion by preventing the loss of manganese ion active species into the solution. In situ characterizations and density functional theory (DFT) studies have revealed effective bimetallic redox cycles at asymmetric Mn-OV-Ce active sites, which promote surface charge transfer, enhance the adsorption reaction activity of active species toward pollutants, and favor PMS activation to generate (•OH, SO4•-, O2•- and 1O2) active species. This study provides a brand-new perspective for engineering the interfacial behavior of PMS activation.

Disulfidptosis and ferroptosis related genes predict prognosis and personalize treatment for hepatocellular carcinoma.

Background: Understanding the interplay between disulfidptosis, ferroptosis, and hepatocellular carcinoma (HCC) could provide valuable insights into the pathogenesis of HCC and potentially identify novel therapeutic targets for the treatment of this deadly disease. This study aimed to identify a prognostic signature for HCC by examining the differential expression of genes related to disulfidptosis and ferroptosis (DRG-FRG), and to assess its clinical applicability. Methods: By integrating 23 disulfidptosis and 259 ferroptosis related genes with HCC messenger RNA (mRNA) expression data from The Cancer Genome Atlas (TCGA), differentially expressed DRG-FRG genes were identified. From these, 11 DRG-FRG genes were selected to construct a risk signature model using least absolute shrinkage and selection operator regression analyses. The prognostic performance of this model was evaluated by Kaplan-Meier survival analysis and time-dependent receiver operating characteristic (ROC) analysis. Subsequently, a nomogram was built by combining the signature with clinical variables. To further delve into the underlying mechanisms, we performed bioinformatics analysis using a variety of databases. Results: A prognostic signature based on 11 DRG-FRG genes effectively categorized HCC patients into high- and low-risk groups, showing a significant survival difference. Even after considering clinical variables, this signature remained an independent prognostic factor. Furthermore, the signature played a role in various critical biological processes and pathways that drive HCC progression. Potential therapeutic benefits could be derived from small molecule drugs targeting NQO1 and SLC7A11. Interestingly, the high-risk group exhibited resistance to several chemotherapeutic drugs, yet showed sensitivity to others when contrasted with the low-risk group. Lastly, the DRG-FRG genes signature had a strong correlation with the tumor immune microenvironment, marked by an elevated expression of immune checkpoint molecules in the high-risk group. Conclusions: The signature based on 11 DRG-FRG genes stands out as a promising prognostic biomarker for HCC. Beyond its predictive value, it sheds light on the intricate crosstalk between DRG-FRG genes and HCC. Importantly, these findings could pave the way for enhanced prognostic prediction, informed treatment decisions, and the advancement of immunotherapy for HCC patients.

Nanomaterials Regulate Bacterial Quorum Sensing: Applications, Mechanisms, and Optimization Strategies.

Anti-virulence therapy that interferes with bacterial communication, known as "quorum sensing (QS)", is a promising strategy for circumventing bacterial resistance. Using nanomaterials to regulate bacterial QS in anti-virulence therapy has attracted much attention, which is mainly attributed to unique physicochemical properties and excellent designability of nanomaterials. However, bacterial QS is a dynamic and multistep process, and there are significant differences in the specific regulatory mechanisms and related influencing factors of nanomaterials in different steps of the QS process. An in-depth understanding of the specific regulatory mechanisms and related influencing factors of nanomaterials in each step can significantly optimize QS regulatory activity and enhance the development of novel nanomaterials with better comprehensive performance. Therefore, this review focuses on the mechanisms by which nanomaterials regulate bacterial QS in the signal supply (including signal synthesis, secretion, and accumulation) and signal transduction cascade (including signal perception and response) processes. Moreover, based on the two key influencing factors (i.e., the nanomaterial itself and the environment), optimization strategies to enhance the QS regulatory activity are comprehensively summarized. Collectively, applying nanomaterials to regulate bacterial QS is a promising strategy for anti-virulence therapy. This review provides reference and inspiration for further research on the anti-virulence application of nanomaterials.

Copper oxides activate peroxymonosulfate for degradation of methylene blue via radical and nonradical pathways: surface structure and mechanism.

A one-step hydrothermal method for preparation of copper oxides with different valences using ascorbic acid as a reducing reagent was developed for environmental remediation. The results suggested that the notable degradation performance of CuO0 may be attributable to the abundant active sites, such as Cu or Cu-O, and was not significantly related to the Cu valence state. In contrast to direct degradation of pollutants by traditional superoxide radicals (O2•-), O2•- played an important role in the reduction of high-valence Cu ions (Cu(III)). In addition, a series of radical quenching, electron paramagnetic resonance (EPR), and electrochemical experiments validated the existence of direct electron transfer between methylene blue (MB) and PMS mediated by CuO0 and surface-bound radicals. The results suggested that the CuO0/PMS system may be less susceptible to diverse ions and natural organic matter other than dihydrogen phosphate anions. The mechanism of MB degradation under alkaline conditions was different from that under acidic conditions in that it was not reliant on radicals or charge transfer but direct oxidation by PMS. This study provides new insights into the heterogeneous processes involved in PMS activation by the copper oxides. Furthermore, this paper devotes to providing theoretical basis on pollutant removal via PMS activated by copper oxides and developing low-cost and high-efficiency catalysts.

MDM2 upregulation induces mitophagy deficiency via Mic60 ubiquitination in fetal microglial inflammation and consequently neuronal DNA damage caused by exposure to ZnO-NPs during pregnancy.

During pregnancy, the human body is quite vulnerable to external stimuli. Zinc oxide nanoparticles (ZnO-NPs) are widely used in daily life, and they enter the human body via environmental or biomedical exposure, thus having potential risks. Although accumulating studies have demonstrated the toxic effects of ZnO-NPs, few studies have addressed the effect of prenatal ZnO-NP exposure on fetal brain tissue development. Here, we systematically studied ZnO-NP-induced fetal brain damage and the underlying mechanism. Using in vivo and in vitro assays, we found that ZnO-NPs could cross the underdeveloped bloodbrain barrier and enter fetal brain tissue, where they could be endocytosed by microglia. ZnO-NP exposure impaired mitochondrial function and induced autophagosome overaccumulation by downregulation of Mic60, thus inducing microglial inflammation. Mechanistically, ZnO-NPs increased Mic60 ubiquitination by activating MDM2, resulting in imbalanced mitochondrial homeostasis. Inhibition of Mic60 ubiquitination by MDM2 silencing significantly attenuated the mitochondrial damage induced by ZnO-NPs, thereby preventing autophagosome overaccumulation and reducing ZnO-NP-mediated inflammation and neuronal DNA damage. Our results demonstrate that ZnO-NPs are likely to disrupt mitochondrial homeostasis, inducing abnormal autophagic flux and microglial inflammation and secondary neuronal damage in the fetus. We hope the information provided in our study will improve the understanding of the effects of prenatal ZnO-NP exposure on fetal brain tissue development and draw more attention to the daily use of and therapeutic exposure to ZnO-NPs among pregnant women.