Syringeable Near-Infrared Light-Activated In Situ Immunogenic Hydrogel Boosts the Cancer-Immunity Cycle to Enhance Anticancer Immunity.

Effective anticancer immunity depends on properly activating multiple stepwise events in the cancer-immunity cycle. An immunologically "cold" tumor microenvironment (TME) engenders immune evasion and refractoriness to conventional checkpoint blockade immunotherapy. Here, we combine nanoparticle formulations and an in situ formed hydrogel scaffold to treat accessible tumors locally and to stimulate systemic immunity against metastatic tumor lesions. The nanoparticles encapsulate poly(ε-caprolactone)-derived cytotoxic chemotherapy and adjuvant of Toll-like receptor 7/8 through a reactive oxygen species (ROS)-cleavable linker that can be self-activated by the coassembled neighboring photosensitizer following near-infrared (NIR) laser irradiation. Further development results in syringeable, NIR light-responsive, and immunogenic hydrogel (iGEL) that can be implanted peritumorally and deposited into the tumor surgical bed. Upon NIR laser irradiation, the generated ROS induces iGEL degradation and bond cleavage in the polymer-drug conjugates, triggering the immunogenic cell death cascade in cancer cells and spontaneously releasing encapsulated agents to rewire the cancer-immunity cycle. Notably, upon application in multiple preclinical models of melanoma and triple-negative breast cancer, which are aggressive and refractory to conventional immunotherapy, iGEL induces durable remission of established tumors, extends postsurgical tumor-free survival, and inhibits metastatic burden. The result of this study is a locally administrable immunogenic hydrogel for triggering host systemic immunity to improve immunotherapeutic efficacy with minimal off-target side effects.

Associations between Geriatric Nutrition Risk Index, bone mineral density and body composition in type 2 diabetes patients.

BACKGROUND: Type 2 diabetes mellitus (T2DM), a fast-growing issue in public health, is one of the most common chronic metabolic disorders in older individuals. Osteoporosis and sarcopenia are highly prevalent in T2DM patients and may result in fractures and disabilities. In people with T2DM, the association between nutrition, sarcopenia, and osteoporosis has rarely been explored. AIM: To evaluate the connections among nutrition, bone mineral density (BMD) and body composition in patients with T2DM. METHODS: We enrolled 689 patients with T2DM for this cross-sectional study. All patients underwent dual energy X-ray absorptiometry (DXA) examination and were categorized according to baseline Geriatric Nutritional Risk Index (GNRI) values calculated from serum albumin levels and body weight. The GNRI was used to evaluate nutritional status, and DXA was used to investigate BMD and body composition. Multivariate forward linear regression analysis was used to identify the factors associated with BMD and skeletal muscle mass index. RESULTS: Of the total patients, 394 were men and 295 were women. Compared with patients in tertile 1, those in tertile 3 who had a high GNRI tended to be younger and had lower HbA1c, higher BMD at all bone sites, and higher appendicular skeletal muscle index (ASMI). These important trends persisted even when the patients were divided into younger and older subgroups. The GNRI was positively related to ASMI (men: r = 0.644, P < 0.001; women: r = 0.649, P < 0.001), total body fat (men: r = 0.453, P < 0.001; women: r = 0.557, P < 0.001), BMD at all bone sites, lumbar spine (L1-L4) BMD (men: r = 0.110, P = 0.029; women: r = 0.256, P < 0.001), FN-BMD (men: r = 0.293, P < 0.001; women: r = 0.273, P < 0.001), and hip BMD (men: r = 0.358, P < 0.001; women: r = 0.377, P < 0.001). After adjustment for other clinical parameters, the GNRI was still significantly associated with BMD at the lumbar spine and femoral neck. Additionally, a low lean mass index and higher ß-collagen special sequence were associated with low BMD at all bone sites. Age was negatively correlated with ASMI, whereas weight was positively correlated with ASMI. CONCLUSION: Poor nutrition, as indicated by a low GNRI, was associated with low levels of ASMI and BMD at all bone sites in T2DM patients. Using the GNRI to evaluate nutritional status and using DXA to investigate body composition in patients with T2DM is of value in assessing bone health and physical performance.

The effect of GnRH analog treatment on BMI in children treated for precocious puberty: a systematic review and meta-analysis.

INTRODUCTION: The purpose of the present meta-analysis was to systematically evaluate the effect of GnRHa treatment on the BMI of children with precocious puberty after GnRHa treatment as compared to before, and to analyze the effect of GnRHa treatment on the body composition of children with precocious puberty at different BMIs by classifying into normal body mass, overweight, and obese groups according to BMI at the time of initial diagnosis. CONTENT: A meta-analysis was performed using Stata 12.0 software by searching PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP database), and Wan fang database for relevant literature on standard deviation score of body mass index (BMI-SDS) after GnRHa treatment as compared to before in children with precocious puberty. SUMMARY: A total of eight studies were included with a total sample size of 715 cases, and the results of meta-analysis showed that BMI-SDS increased in children with precocious puberty after GnRHa treatment as compared to before starting [(weighted mean difference (WMD)=0.23, 95 % CI: 0.14-0.33, p=0.000)] and also increased in children with normal body mass [(WMD=0.37, 95 % CI: 0.28-0.46, p=0.000)], and there was no significant change in BMI-SDS in children in the overweight or obese group [(WMD=0.01, 95 % CI: -0.08-0.10, p=0.775)]. OUTLOOK: Overall, there was an observed increase in BMI-SDS at the conclusion of GnRHa treatment in children with precocious puberty. Additionally, it was found that the effect of GnRHa treatment on body composition varied among children with different BMI status. Clinicians should emphasize the promotion of a healthy lifestyle and personalized dietary management for children.

LncRNA ZNF674-AS1 drives cell growth and inhibits cisplatin-induced pyroptosis via up-regulating CA9 in neuroblastoma.

Neuroblastoma (NB) is a challenging pediatric extracranial solid tumor characterized by a poor prognosis and resistance to chemotherapy. Identifying targets to enhance chemotherapy sensitivity in NB is of utmost importance. Increasing evidence implicates long noncoding RNAs (lncRNAs) play important roles in cancer, but their functional roles remain largely unexplored. Here, we analyzed our RNA sequencing data and identified the upregulated lncRNA ZNF674-AS1 in chemotherapy non-responsive NB patients. Elevated ZNF674-AS1 expression is associated with poor prognosis and high-risk NB. Importantly, targeting ZNF674-AS1 expression in NB cells suppressed tumor growth in vivo. Further functional studies have revealed that ZNF674-AS1 constrains cisplatin sensitivity by suppressing pyroptosis and promoting cell proliferation. Moreover, ZNF674-AS1 primarily relies on CA9 to fulfill its functions on cisplatin resistance. High CA9 levels were associated with high-risk NB and predicted poor patient outcomes. Mechanistically, ZNF674-AS1 directly interacted with the RNA binding protein IGF2BP3 to enhance the stability of CA9 mRNA by binding with CA9 transcript, leading to elevated CA9 expression. As a novel regulator of CA9, IGF2BP3 positively upregulated CA9 expression. Together, these results expand our understanding of the cancer-associated function of lncRNAs, highlighting the ZNF674-AS1/IGF2BP3/CA9 axis as a constituting regulatory mode in NB tumor growth and cisplatin resistance. These insights reveal the pivotal role of ZNF674-AS1 inhibition in recovering cisplatin sensitivity, thus providing potential therapeutic targets for NB treatment.

Role of the In-Situ-Formed Surface (Pt-S-O)-Ti Active Structure in SO2-Promoted C3H8 Combustion over a Pt/TiO2 Catalyst.

Typically, SO2 unavoidably deactivates catalysts in most heterogeneous catalytic oxidations. However, for Pt-based catalysts, SO2 exhibits an extraordinary boosting effect in propane catalytic oxidation, but the promotive mechanism remains contentious. In this study, an in situ-formed tactful (Pt-S-O)-Ti structure was concluded to be a key factor for Pt/TiO2 catalysts with a substantial SO2 tolerance ability. The experiments and theoretical calculations confirm that the high degree of hybridization and orbital coupling between Pt 5d and S 3p orbitals enable more charge transfer from Pt to S species, thus forming the (Pt-S-O)-Ti structure with the oxygen atom dissociated from the chemisorbed O2 adsorbed on oxygen vacancies. The active oxygen atom in the (Pt-S-O)-Ti active structure is a robust site for C3H8 adsorption, leading to a better C3H8 combustion performance. This work can provide insights into the rational design of chemical bonds for high SO2 tolerance catalysts, thereby improving economic and environmental benefits.

Gliclazide Ameliorates Neuronal Injury by Attenuating Oxidative Stress in D-gal-Induced Senescent Cells and Aging Mice.

Enhancement of oxidative stress and resultant neuronal injury play important roles in initiating cognitive impairment during the aging process. Thus, attenuating oxidative injury is regarded as a profitable therapeutic strategy for age-associated cognitive impairment. Previous studies showed that gliclazide (Gli) had a protective role in neuronal injury from cerebral ischemia/reperfusion (I/R) injury. However, whether Gli has a profitable effect on age-associated cognitive impairment remains largely unclear. The present study showed that Gli held the potential to attenuate neuronal apoptosis in D-gal-induced senescent cells and aging mice. Additionally, Gli could alleviate synaptic injury and cognitive function in D-gal-induced aging mice. Further study showed that Gli could attenuate oxidative stress in D-gal-induced senescent cells and aging mice. The p38 MAPK pathway was predicted as the downstream target of Gli retarding oxidative stress using in silico analysis. Further studies revealed that Gli attenuated D-gal-induced phosphorylation of p38 and facilitated Nrf2 nuclear expression, indicating that the anti-oxidative property of Gli may be associated with the p38 MAPK pathway. The study demonstrates that Gli has a beneficial effect on ameliorating D-gal-induced neuronal injury and cognitive impairment, making this compound a promising agent for the prevention and treatment of age-associated cognitive impairment.

Facile Synthesis of 2D SiOx -3D Si Hybrid Anode Materials by Ca Modification Effect for Enhanced Lithium Storage Performance.

Al-Si dealloying method is widely used to prepare Si anode for alleviating the issues caused by a drastic volume change of Si-based anode. However, this method suffers from the problems of low Si powder yield (<20 wt.% Si) and complicated cooling equipment due to the hindrance of large-size primary Si particles. Here, a new modification strategy to convert primary Si to 2D SiOx nanosheets by introducing a Ca modifier into Al-Si alloy melt is presented. The thermodynamics calculation shows that the primary Si is preferentially converted to CaAl2 Si2 intermetallic compound in Al-Si-Ca alloy system. After the dealloying process, the CaAl2 Si2 is further converted to 2D SiOx nanosheets, and eutectic Si is converted to 3D Si, thus obtaining the 2D SiOx -3D Si hybrid Si-based materials (HSiBM). Benefiting from the modification effect, the HSiBM anode shows a significantly improved electrochemical performance, which delivers a capacity retention of over 90% after 100 cycles and keeps 98.94% capacity after the rate test. This work exhibits an innovative approach to produce stable Si-based anode through Al-Si dealloying method with a high Si yield and without complicated rapid cooling techniques, which has a certain significance for the scalable production of Si-based anodes.

The utility of quantitative computed tomography in cohort studies of chronic obstructive pulmonary disease: a narrative review.

Background and Objective: Chronic obstructive pulmonary disease (COPD) is a significant contributor to global morbidity and mortality. Quantitative computed tomography (QCT), a non-invasive imaging modality, offers the potential to assess lung structure and function in COPD patients. Amidst the coronavirus disease 2019 (COVID-19) pandemic, chest computed tomography (CT) scans have emerged as a viable alternative for assessing pulmonary function (e.g., spirometry), minimizing the risk of aerosolized virus transmission. However, the clinical application of QCT measurements is not yet widespread enough, necessitating broader validation to determine its usefulness in COPD management. Methods: We conducted a search in the PubMed database in English from January 1, 2013 to April 20, 2023, using keywords and controlled vocabulary related to QCT, COPD, and cohort studies. Key Content and Findings: Existing studies have demonstrated the potential of QCT in providing valuable information on lung volume, airway geometry, airway wall thickness, emphysema, and lung tissue density in COPD patients. Moreover, QCT values have shown robust correlations with pulmonary function tests, and can predict exacerbation risk and mortality in patients with COPD. QCT can even discern COPD subtypes based on phenotypic characteristics such as emphysema predominance, supporting targeted management and interventions. Conclusions: QCT has shown promise in cohort studies related to COPD, since it can provide critical insights into the pathogenesis and progression of the disease. Further research is necessary to determine the clinical significance of QCT measurements for COPD management.

Selection and validation of optimal reference genes for RT-qPCR analyses in Aphidoletes aphidimyza Rondani (Diptera: Cecidomyiidae).

Aphidoletes aphidimyza is a predator that is an important biological agent used to control agricultural and forestry aphids. Although many studies have investigated its biological and ecological characteristics, few molecular studies have been reported. The current study was performed to identify suitable reference genes to facilitate future gene expression and function analyses via quantitative reverse transcription PCR. Eight reference genes glyceraldehyde-3-phosphate dehydrogenase (GAPDH), RPS13, RPL8, RPS3, α-Tub, ß-actin, RPL32, and elongation factor 1 alpha (EF1-α) were selected. Their expression levels were determined under four different experimental conditions (developmental stages, adult tissues, sugar treatment, and starvation treatment) using qRT-PCR technology. The stability was evaluated with five methods (Ct value, geNorm, NormFinder, BestKeeper, and RefFinder). The results showed that GAPDH, RPL32, and EF1-α were ranked as the best reference gene combinations for measuring gene expression levels among different developing stages and in various starvation treatments. RPL8 and RPS3 were recommended to normalize the gene expression levels among different adult tissues. RPL32, ß-actin, and EF1-α were recommended sugar-feeding conditions. To validate the utility of the selected reference pair, RPL8, and RPS3, we estimated the tissue-biased expression level of a chemosensory protein gene (AaphCSP1). As expected, AaphCSP1 is highly expressed in the antennae and lowly expressed in the abdomen. These findings will lay the foundation for future research on the molecular physiology and biochemistry of A. aphidimyza.

An entropy weight method to integrate big omics and mechanistically evaluate DILI.

BACKGROUND AND AIMS: DILI accounts for more than half of acute liver failure cases in the United States and is a major health care issue for the public worldwide. As investigative toxicology is playing an evolving role in the pharmaceutical industry, mechanistic insights into drug hepatotoxicity can facilitate drug development and clinical medication. METHODS: By integrating multisource datasets including gene expression profiles of rat livers from open TG-GATE database and DrugMatrix, drug labels from FDA Liver Toxicity Knowledge Base, and clinical reports from LiverTox, and with the employment of bioinformatic and computational tools, this study developed an approach to characterize and predict DILI based on the molecular understanding of the processes (toxicity pathways). RESULTS: A panel of 11 pathways widely covering biological processes and stress responses was established using a training set of six positive and one negative DILI drugs from open TG-GATEs. An entropy weight method-based model was developed to weight responsive genes within a pathway, and an interpretable machine-learning (ML) model XGBoot-SHAP was trained to rank the importance of pathways to the panel activity. The panel activity was proven to differentiate between injured and noninjured sample points and characterize DILI manifestation using six training drugs. Next, the model was tested using an additional 89 drugs (61 positives + 28 negatives), and a precision of 86% and higher can be achieved. CONCLUSIONS: This study provides a novel approach to mechanisms-driven prediction modeling, as well as big data integration for insights into pharmacology and other human biology areas.

SUMOylation of SMAD4 by PIAS1 in Conjunction with Vimentin Upregulation Promotes Migration Potential in Non-Small Cell Lung Cancer.

BACKGROUND: The expression of vimentin as a marker of epithelial-to-mesenchymal transition (EMT) has been speculated to be associated with tissue heterogeneity and metastases of non-small cell lung cancer (NSCLC). METHODS: This study utilized in vitro co-immunoprecipitation with small interfering RNAs (siRNAs) against protein inhibitors of STAT system type 1 (PIAS1) or SMAD4 in transforming growth factor-beta (TGF-ß) signaling pathway in combination with SUMOylation assay. RESULTS: We successfully demonstrated that PIAS1 enhanced SUMOylation of SMAD4 by forming a complex PIAS1-SUMO1-SMAD4 protein complex. This, in accordance with subsequently increased production of vimentin microfilaments, led to enhanced migration ability of non-small cell lung cancer (NSCLC) A549 line, observed from wound healing assay. CONCLUSIONS: Our results further supported the positive correlation of SUMOylated SMAD4 mediated by PIAS1 and downstream overexpression of vimentin. In addition, the observation that overexpression of vimentin in this certain cell line was not necessarily linked with accelerated relative wound closure raised concerns that further exploration will be needed to confirm if the causal relationship exists between vimentin expression and the metastases of NSCLC, and if so, to what extent vimentin contributes to it.

Ferroptosis contributes to ethanol-induced hepatic cell death via labile iron accumulation and GPx4 inactivation.

Alcohol abuse is a significant cause of global morbidity and mortality, with alcoholic liver disease (ALD) being a common consequence. The pathogenesis of ALD involves various cellular processes, including oxidative stress, inflammation, and hepatic cell death. Recently, ferroptosis, an iron-dependent form of programmed cell death, has emerged as a potential mechanism in many diseases. However, the specific involvement and regulatory mechanisms of ferroptosis in ALD remain poorly understood. Here we aimed to investigate the presence and mechanism of alcohol-induced ferroptosis and the involvement of miRNAs in regulating ferroptosis sensitivity. Our findings revealed that long-term ethanol feeding induced ferroptosis in male mice, as evidenced by increased expression of ferroptosis-related genes, lipid peroxidation, and labile iron accumulation in the liver. Furthermore, we identified dysregulation of the methionine cycle and transsulfuration pathway, leading to severe glutathione (GSH) exhaustion and indirect deactivation of glutathione peroxidase 4 (GPx4), a critical enzyme in preventing ferroptosis. Additionally, we identified miR-214 as a ferroptosis regulator in ALD, enhancing hepatocyte ferroptosis by transcriptionally activating the expression of ferroptosis-driver genes. Our study provides novel insights into the involvement and regulatory mechanisms of ferroptosis in ALD, highlighting the potential therapeutic implications of targeting ferroptosis and miRNAs in ALD management.

Early Prediction of Epilepsy after Encephalitis in Childhood Based on EEG and Clinical Features.

Objective: The present study was designed to establish and evaluate an early prediction model of epilepsy after encephalitis in childhood based on electroencephalogram (ECG) and clinical features. Methods: 255 patients with encephalitis were randomly divided into training and verification sets and were divided into postencephalitic epilepsy (PE) and no postencephalitic epilepsy (no-PE) according to whether epilepsy occurred one year after discharge. Univariate and multivariate logistic regression analyses were used to screen the risk factors for PE. The identified risk factors were used to establish and verify a model. Results: This study included 255 patients with encephalitis, including 209 in the non-PE group and 46 in the PE group. Univariate and multiple logistic regression analysis showed that hemoglobin (OR = 0.968, 95% CI = 0.951-0.958), epilepsy frequency (OR = 0.968, 95% CI = 0.951-0.958), and ECG slow wave/fast wave frequency (S/F) in the occipital region were independent influencing factors for PE (P < 0.05).The prediction model is based on the above factors: -0.031 × hemoglobin -2.113 × epilepsy frequency + 7.836 × occipital region S/F + 1.595. In the training set and the validation set, the area under the ROC curve (AUC) of the model for the diagnosis of PE was 0.835 and 0.712, respectively. Conclusion: The peripheral blood hemoglobin, the number of epileptic seizures in the acute stage of encephalitis, and EEG slow wave/fast wave frequencies can be used as predictors of epilepsy after encephalitis.

Diesel exhaust particles exposure induces liver dysfunction: Exploring predictive potential of human circulating microRNAs signature relevant to liver injury risk.

Diesel exhaust particles (DEP) pollution should be taken seriously because it is an extensive environmental and occupational health concern. Exploring early effect biomarkers is crucial for monitoring and managing DEP-associated health risk assessment. Here, we found that serum levels of 67 miRNAs were dysregulated in DEP exposure group. Notably, 20 miRNAs were identified as each having a significant dose-response relationship with the internal exposure level of DEP. Further, we revealed that the DEP exposure could affect the liver function of subjects and that 7 miRNAs (including the well-known liver injury indicator, miR-122-5p) could serve as the novel epigenetic-biomarkers (epi-biomarkers) to reflect the liver-specific response to the DEP exposure. Importantly, an unprecedented prediction model using these 7 miRNAs was established for the assessment of DEP-induced liver injury risk. Finally, bioinformatic analysis indicated that the unique set of miRNA panel in serum might also contribute to the molecular mechanism of DEP exposure-induced liver damage. These results broaden our understanding of the adverse health outcomes of DEP exposure. Noteworthy, we believe this study could shed light on roles and functions of epigenetic biomarkers from environmental exposure to health outcomes by revealing the full chain of exposure-miRNAs-molecular pathways-disease evidence.

Transcriptomic Heterogeneity of Human Mesenchymal Stem Cells Derived from Bone Marrow, Dental Pulp, Adipose Tissue, and Umbilical Cord.

Compared with mesenchymal stem cells (MSCs) obtained from other tissue sources, those derived from umbilical cord (UC) tissue exhibit numerous advantages and vast potential for therapeutic applications. However, MSCs from different tissue sources are heterogeneous, and therefore, the therapeutic efficacy of UC-derived MSCs as a replacement for other tissue-derived MSCs needs to be studied. To better understand the distinctions between UC-derived MSCs and MSCs derived from other tissues, we conducted a transcriptome analysis of MSCs obtained from UC and three other tissues. Correlation analysis revealed the strongest correlation between UC-MSCs (UC-MSCs) and bone marrow-MSCs (BM-MSCs). Compared with UC-MSCs, the lower differentially expressed genes of BM-MSCs, dental pulp-MSCs (DP-MSCs), and adipose tissue-MSCs (AP-MSCs) were predominantly enriched in actin-related terms, while higher differentially expressed genes were predominantly enriched in immunological processes. We also analyzed the distribution of 34 frequently or highly expressed cell characterization molecules in BM-MSCs, DP-MSCs, AP-MSCs, and UC-MSCs. CD200 (FPKM >10) was only detected in UC-MSCs, while CD106 was detected in AD-MSCs and DP-MSCs (FPKM >10). The reliability of transcriptomic data analysis was verified by quantitative real-time PCR. Finally, we recommend the use of CD200, CD106, and other similar markers with unstable expression as benchmark molecules to monitor the proliferation and differentiation potential of MSCs. This study provides comprehensive insights into the heterogeneity between UC-MSCs and MSCs derived from other tissues, which can guide the therapeutic application of UC-MSCs.

Reversible Diode with Tunable Band Alignment for Photoelectricity-Induced Artificial Synapse.

The advent of big data era has put forward higher requirements for electronic nanodevices that have low energy consumption for their application in analog computing with memory and logic circuit to address attendant energy efficiency issues. Here, a miniaturized diode with a reversible switching state based on N-n MoS2 homojunction used a bandgap renormalization effect through the band alignment type regulated by both dielectric and polarization, controllably switched between type-I and type-II, which can be simulated as artificial synapse for sensing memory processing because of its rectification, nonvolatile characteristic and high optical responsiveness. The device demonstrates a rectification ratio of 103 . When served as memory retention time, it can attain at least 7000 s. For the synapse simulation, it has an ultralow-level energy consumption because of the pA-level operation current with 5 pJ for long-term potentiation and 7.8 fJ for long-term depression. Furthermore, the paired pulse facilitation index reaches up to 230%, and it realizes the function of optical storage that can be applied to simulate visual cells.

Dynamics of histone acetylation during human early embryogenesis.

It remains poorly understood about the regulation of gene and transposon transcription during human early embryogenesis. Here, we report that broad H3K27ac domains are genome-widely distributed in human 2-cell and 4-cell embryos and transit into typical peaks in the 8-cell embryos. The broad H3K27ac domains in early embryos before zygotic genome activation (ZGA) are also observed in mouse. It suggests that broad H3K27ac domains play conserved functions before ZGA in mammals. Intriguingly, a large portion of broad H3K27ac domains overlap with broad H3K4me3 domains. Further investigation reveals that histone deacetylases are required for the removal or transition of broad H3K27ac domains and ZGA. After ZGA, the number of typical H3K27ac peaks is dynamic, which is associated with the stage-specific gene expression. Furthermore, P300 is important for the establishment of H3K27ac peaks and the expression of associated genes in early embryos after ZGA. Our data also indicate that H3K27ac marks active transposons in early embryos. Interestingly, H3K27ac and H3K18ac signals rather than H3K9ac signals are enriched at ERVK elements in mouse embryos after ZGA. It suggests that different types of histone acetylations exert distinct roles in the activation of transposons. In summary, H3K27ac modification undergoes extensive reprogramming during early embryo development in mammals, which is associated with the expression of genes and transposons.

Using a human bronchial epithelial cell-based malignant transformation model to explore the function of hsa-miR-200 family in the progress of PM2.5-induced lung cancer development.

Numerous studies have revealed that ambient long-term exposure to fine particulate matter (PM2.5) is significantly related to the development of lung cancer, but the molecular mechanisms of PM2.5 exposure-induced lung cancer remains unknown. As an important epigenetic regulator, microRNAs (miRNAs) play vital roles in responding to environment exposure and various diseases including lung cancer development. Here we constructed a PM2.5-induced malignant transformed cell model and found that miR-200 family, especially miR-200a-3p, was involved in the process of PM2.5 induced lung cancer. Further investigation of the function of miR-200 family (miR-200a-3p as a representative revealed that miR-200a-3p promoted cell migration by directly suppressing TNS3 expression. These results suggested that ambient PM2.5 exposure may increase the expression of miR-200 family and then promote the proliferation and migration of lung cancer cells. Our study provided novel model and insights into the molecular mechanism of ambient PM2.5 exposure-induced lung cancer.

Noncoding RNA circBtnl1 suppresses self-renewal of intestinal stem cells via disruption of Atf4 mRNA stability.

Intestinal stem cells (ISCs) at the crypt base are responsible for the regeneration of the intestinal epithelium. However, how ISC self-renewal is regulated still remains unclear. Here we identified a circular RNA, circBtnl1, that is highly expressed in ISCs. Loss of circBtnl1 in mice enhanced ISC self-renewal capacity and epithelial regeneration, without changes in mRNA and protein levels of its parental gene Btnl1. Mechanistically, circBtnl1 and Atf4 mRNA competitively bound the ATP-dependent RNA helicase Ddx3y to impair the stability of Atf4 mRNA in wild-type ISCs. Furthermore, ATF4 activated Sox9 transcription by binding to its promoter via a unique motif, to enhance the self-renewal capacity and epithelial regeneration of ISCs. In contrast, circBtnl1 knockout promoted Atf4 mRNA stability and enhanced ATF4 expression, which caused Sox9 transcription to potentiate ISC stemness. These data indicate that circBtnl1-mediated Atf4 mRNA decay suppresses Sox9 transcription that negatively modulates self-renewal maintenance of ISCs.

Sodium butyrate protects against rotavirus-induced intestinal epithelial barrier damage by activating AMPK-Nrf2 signaling pathway in IPEC-J2 cells.

Rotavirus (RV) mainly infects intestinal epithelial cells, which leads to diarrhea in newborn piglets with dysfunction in the intestinal mucosal mechanical barrier. Sodium butyrate (SB) is one of the metabolites excreted by gut microbes. However, the protective effect of SB on RV infection induced intestinal mucosal mechanical barrier injury and its potential mechanism has not been well elucidated. In the present study, IPEC-J2 cells with RV infection was a model of intestinal mucosal mechanical barrier injury. Our results demonstrated that the appropriate concentration of SB can effectively alleviate TJ structural damage and up-regulating the expression of TJ-related genes. Furthermore, the appropriate concentration of SB can effectively reverse the increase of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) level induced by RV infection. Meanwhile, the levels of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-px) and antioxidant proteins NAD(P)H dehydrogenase quinone 1 (NQO1) and heme oxygenase-1 (HO-1) were increased through SB treatment. In addition, we found that SB increased cellular antioxidant capacity by activating the adenosine monophosphate-activated protein kinase (AMPK)-nuclear factor erythroid 2-related factor (Nrf2) signaling pathway and the cytoprotective effect of SB is limited by GPR109A siRNA. Thus, our findings revealed that SB reduces oxidative stress caused by RV infection and restores the intestinal mucosal mechanical barrier function by activating the AMPK-Nrf2 signal pathway mediated by the receptor GPR109A.