Eriocalyxin B alleviated ischemic cerebral injury by limiting microglia-mediated excessive neuroinflammation in mice.

Excessive neuroinflammation mediated by microglia has a detrimental effect on the progression of ischemic stroke. Eriocalyxin B (EriB) was found with a neuroprotective effect in mice with Parkinson's disease via the suppression of microglial overactivation. This study aimed to investigate the roles of EriB in permanent middle cerebral artery occlusion (pMCAO) mice. The pMCAO was induced in the internal carotid artery of the mice by the intraluminal filament method, and EriB (10 mg/kg) was administered immediately after surgery by intraperitoneal injection. The behavior score, 2,3,5-triphenyltetrazole chloride staining, Nissl staining, TUNEL, immunohistochemistry, immunofluorescence, PCR, ELISA, and immunoblotting revealed that EriB administration reduced brain infarct and neuron death and ameliorated neuroinflammation and microglia overactivation in pMCAO mice, manifested by alterations of TUNEL-positive cell numbers, ionized calcium binding adaptor molecule 1 (Iba-1)-positive cell numbers, and expression of tumor necrosis factor-α, interleukin 6, IL-1ß, inducible nitric oxide synthase, and arginase 1. In addition, EriB suppressed ischemia-induced activation of nuclear factor kappa B (NF-κB) signaling in the brain penumbra, suggesting the involvement of NF-κB in EriB function. In conclusion, EriB exerted anti-inflammatory effects in ischemia stroke by regulating the NF-κB signaling pathway, and this may provide insights into the neuroprotective effect of EriB in the treatment of ischemic stroke.

The paracrine isthmin1 transcriptionally regulated by C/EBPß exacerbates pulmonary vascular leakage in murine sepsis.

It is known that pulmonary vascular leakage, a key pathological feature of sepsis-induced lung injury, is largely regulated by perivascular cells. However, the underlying mechanisms have not been fully uncovered. In the present study, we aimed to evaluate the role of isthmin1, a secretory protein originating from alveolar epithelium, in the pulmonary vascular leakage during sepsis and to investigate the regulatory mechanisms of isthmin1 gene transcription. We observed an elevated isthmin1 gene expression in the pulmonary tissue of septic mice induced by cecal ligation and puncture (CLP), as well as in primary murine alveolar type II epithelial cells (ATII) exposed to lipopolysaccharide (LPS). Furthermore, we confirmed that isthmin1 derived from ATII contributes to pulmonary vascular leakage during sepsis. Specifically, adenovirus-mediated isthmin1 disruption in ATII led to a significant attenuation of the increased pulmonary microvascular endothelial cell (PMVEC) hyperpermeability in a PMVEC/ATII coculture system when exposed to LPS. In addition, adeno-associated virus 9 (AAV9)-mediated knockdown of isthmin1 in the alveolar epithelium of septic mice significantly attenuated pulmonary vascular leakage. Finally, mechanistic studies unveiled that nuclear transcription factor CCAAT/enhancer binding protein (C/EBP)ß participates in isthmin1 gene activation by binding directly to the cis-regulatory element of isthmin1 locus and may contribute to isthmin1 upregulation during sepsis. Collectively, the present study highlighted the impact of the paracrine protein isthmin1, derived from ATII, on the exacerbation of pulmonary vascular permeability in sepsis and revealed a new regulatory mechanism for isthmin1 gene transcription.NEW & NOTEWORTHY This article addresses the role of the alveolar epithelial-secreted protein isthmin1 on the exacerbation of pulmonary vascular permeability in sepsis and identified nuclear factor CCAAT/enhancer binding protein (C/EBP)ß as a new regulator of isthmin1 gene transcription. Targeting the C/EBPß-isthmin1 regulatory axis on the alveolar side would be of great value in the treatment of pulmonary vascular leakage and lung injury induced by sepsis.

Dental pulp stem cells induce anti-inflammatory phenotypic transformation of macrophages to enhance osteogenic potential via IL-6/GP130/STAT3 signaling.

Background: Periodontitis is a major oral condition and current treatment outcomes can be unsatisfactory. Macrophages are essential to the regeneration process, so we investigated the influence of human dental pulp stem cells (hDPSCs) on macrophage differentiation and the microenvironment and the underlying mechanism. Methods: hDPSCs were isolated from healthy third molars extracted from patients undergoing maxillofacial surgery. The surface antigens CD73, CD45, CD90 and CD11b of the hDPSCs were detected using flow cytometry. hDPSCs were induced for osteogenic and adipogenic differentiation, and the outcome was assessed by alizarin red staining or Oil Red O staining. The IL-6 level released by hDPSCs was measured by enzyme linked immunosorbent assay (ELISA). Tohoku Hospital Pediatrics-1 (THP-1) cells were cultured and induced into macrophages by phorbol-12-myristate-13-acetate. After coculture of THP-1-derived macrophages with hDPSCs, interleukin 6 (IL-6), Argininase-1 (Arg-1), Mannose receptor C-1 (Mrc-1), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-α (TNF-α) levels in the medium were measured using ELISA and quantificational RT-PCR (qRT-PCR). The numbers of CD80+ and CD163+ macrophages were counted by immunofluorescence, and GP130/STAT3 signaling protein expression was detected. After coculturing the culture medium of hDPSCs with human bone marrow stem cells (BMSCs), scratch assays and transwell assays were performed to evaluate cell migration and invasion. Results: Alkaline phosphatase (ALP) staining, alizarin red staining, and western blots were performed to assess osteoblast differentiation. The hDPSCs were positive for surface antigens CD73 and CD90 and negative for CD45 and CD11b expression. The level of IL-6 secreted by hDPSCs significantly increased the number of CD80+ cells as well as the levels of Arg-1 and Mrc-1. It also promoted M2 macrophage polarization and activated GP130/STAT3 signaling. However, the medium cocultured with THP-1-derived macrophages by hDPSCs facilitated the migration, invasion, and osteogenic abilities of human bone marrow-derived stem cells (hBMSCs). Conclusions: hDPSCs can regulate the periodontal microenvironment through IL-6 by inducing phenotypic transformation of M2 macrophages and stimulating osteogenic differentiation of BMSCs.

Therapeutic effects of atorvastatin on doxorubicin-induced hepatotoxicity in rats via antioxidative damage, anti-inflammatory, and anti-lipotoxicity.

Doxorubicin (DOX), is a high efficiency anthracycline antitumor drug. However, the clinical application of DOX is limited mainly by dose-related adverse drug reactions. Currently, the therapeutic effects of Atorvastatin (ATO) on DOX-induced hepatotoxicity were studied in vivo. The results indicated that DOX impaired hepatic function, as measured by an increased levels of liver weight index and serum concentrations of aspartate transaminase and alanine transaminase, as well as alteration of hepatic histology. In addition, DOX increased the serum levles of triglyceride (TG) and nonestesterified fatty acid. ATO prevented these changes. Mechanical analysis revealed that ATO restored the changes of malondialdehyde, reactive oxygen radical species, glutathione peroxidase and manganese superoxide dismutase. Additionally, ATO inhibited the increased expression levels of nuclear factor-kappa B and interleukin 1ß, hence suppressing inflammation. Meanwhile, ATO inhibited cell apoptosis by dramatically decreasing the Bax/Bcl-2 ratio. In addition, ATO mitigated the lipidtoxicity by inhibiting the adipolysis of TG and accelerating hepatic lipid metabolism. Taken together, the results suggest ATO has therapeutic effect on DOX-induced hepatotoxicity via inhibition of oxidative damage, inflammatory and apoptosis. In addition, ATO attenuates DOX-induced hyperlipidemia via modulation of lipid metabolism.

Efficacy and safety evaluations of anlotinib in patients with advanced non-small cell lung cancer treated with bevacizumab.

Objective: The purpose of this study is to evaluate the efficacy and safety of anlotinib in patients with advanced non-small cell lung cancer (NSCLC) who had previously received bevacizumab. Methods: The participants were histopathologically or cytologically diagnosed advanced NSCLC patients whose disease progressed after at least one type of systemic therapy and who had previously received bevacizumab treatment. The patients were on 3-week administration cycles, including 2 weeks on-treatment (12 mg anlotinib oral route, once a day) and 1 week off-treatment. The primary end point of the trial was overall survival (OS). The secondary end points were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and safety. Results: As of the data collection deadline (31 March 2021), 30 patients were enrolled in the study and received anlotinib treatment. All patients were included in the data set except one, who withdrew their consent after the start of treatment. The median follow-up period was 12.1 months (range, 3.6-25.0 months), and 29 patients were included in the evaluation of the treatment. Of the 29 patients, no CR cases occurred. In total, three patients (10.2%) showed a PR, 21 (72.4%) had SD, and five patients (17.2%) had PD. The objective response rate (ORR) was 10.2% (3 of 29 patients), and the disease control rate (DCR) was 82.7% (24 of 29 patients). The median progression-free survival (PFS) was 5.6 months (95% CI, 5.0-6.1 months; Figure 2). The median overall survival (OS) was 10.6 months (95% CI, 9.4-11.8 months; Figure 3). The overall tolerance of the anlotinib treatment was high among the enrolled patients. No treatment-related grade four or five toxicities were observed. Of the 29 patients, one patient's anlotinib administration was reduced to 8 mg/day due to hypertension and headache. Most adverse events (AEs) were grade one or two; the most common AEs were fatigue (51.7%), hypertension (41.3%), hand-foot syndrome (41.4%), anorexia (34.5%) and hypertriglyceridemia (34.5%). Conclusion: Anlotinib demonstrated favourable activity and manageable toxicity in NSCLC patients who were treated with bevacizumab previously.

TRIM16 exerts protective function on myocardial ischemia/reperfusion injury through reducing pyroptosis and inflammation via NLRP3 signaling.

Myocardial infarction is still a leading cause of morbidity and mortality worldwide, but its pathogenesis has not been fully understood. In the study, we attempted to explore the effects of E3 ligase tripartite motif 16 (TRIM16) on myocardial ischemia-reperfusion (MI/R) injury in vivo and in vitro, and the underlying mechanisms. We identified that TRIM16 was indeed a potent regulator during MI/R progression in murine models and surprisingly showed a negative correlation with the concentrations of cardiac pro-inflammatory cytokines. Adenoviral vectors encoding GFP or TRIM16 (Ad-TRIM16) were subjected to mice through direct injection into the left ventricular (LV). We found that Ad-TRIM16 significantly reduced the infarct size, and improved the cardiac function and structure compared with the Ad-GFP mice after MI/R operation. More studies indicated that TRIM16 over-expression strongly meliorated nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and associated inflammatory response in hearts of MI/R-induced mice, which were validated in hypoxia/reoxygenation (H/R)-exposed primary cardiomyocytes in vitro. In particular, MI/R operation led to cardiac pyroptosis by increasing the cleavage of Caspase-1 and Gasdermin D (GSDMD), while being considerably abrogated upon TRIM16 over-expression. Mechanistically, TRIM16 interacted with NLRP3 and promoted the K48-linked polyubiquitination of NLRP3, ultimately promoted its degradation. Together, we identified TRIM16 as a novel E3 ubiquitin ligase for NLRP3, which played an essential role in modulating its expression, and subsequently influenced inflammatory response and pyroptosis in MI/R murine model, confirming that TRIM16 may be a potential therapeutic target for myocardial infarction.

Exploration of the relationship between hippocampus and immune system in schizophrenia based on immune infiltration analysis.

Immune dysfunction has been implicated in the pathogenesis of schizophrenia (SZ). Despite previous studies showing a broad link between immune dysregulation and the central nervous system of SZ, the exact relationship has not been completely elucidated. With immune infiltration analysis as an entry point, this study aimed to explore the relationship between schizophrenia and the immune system in more detail from brain regions, immune cells, genes, and pathways. Here, we comprehensively analyzed the hippocampus (HPC), prefrontal cortex (PFC), and striatum (STR) between SZ and control groups. Differentially expressed genes (DEGs) and functional enrichment analysis showed that three brain regions were closely related to the immune system. Compared with PFC and STR, there were 20 immune-related genes (IRGs) and 42 immune pathways in HPC. The results of immune infiltration analysis showed that the differential immune cells in HPC were effector memory T (Tem) cells. The correlation of immune-related DEGs (IDEGs) and immune cells further analysis showed that NPY, BLNK, OXTR, and FGF12, were moderately correlated with Tem cells. Functional pathway analysis indicated that these four genes might affect Tem by regulating the PI3K-AKT pathway and the neuroactive ligand-receptor interaction pathway. The receiver operating characteristic curve (ROC) analysis results indicated that these four genes had a high diagnostic ability (AUC=95.19%). Finally, the disease animal model was successfully replicated, and further validation was conducted using the real-time PCR and the western blot. These results showed that these gene expression changes were consistent with our previous expression profiling. In conclusion, our findings suggested that HPC in SZ may be more closely related to immune disorders and modulate immune function through Tem, PI3K-Akt pathway, and neuroactive ligand-binding receptor interactions. To the best of our knowledge, the Immucell AI tool has been applied for the first time to analyze immune infiltration in SZ, contributing to a better understanding of the role of immune dysfunction in SZ from a new perspective.

CircZDBF2 up-regulates RNF145 by ceRNA model and recruits CEBPB to accelerate oral squamous cell carcinoma progression via NFκB signaling pathway.

BACKGROUND: Oral squamous cell carcinoma (OSCC), as one of the commonest malignancies showing poor prognosis, has been increasingly suggested to be modulated by circular RNAs (circRNAs). Through GEO (Gene Expression Omnibus) database, a circRNA derived from ZDBF2 (circZDBF2) was uncovered to be with high expression in OSCC tissues, while how it may function in OSCC remains unclear. METHODS: CircZDBF2 expression was firstly verified in OSCC cells via qRT-PCR. CCK-8, along with colony formation, wound healing, transwell and western blot assays was performed to assess the malignant cell behaviors in OSCC cells. Further, RNA pull down assay, RIP assay, as well as luciferase reporter assay was performed to testify the interaction between circZDBF2 and RNAs. RESULTS: CircZDBF2 expressed at a high level in OSCC cells and it accelerated OSCC cell proliferation, migration, invasion as well as EMT (epithelial-mesenchymal transition) process. Further, circZDBF2 sponged miR-362-5p and miR-500b-5p in OSCC cells to release their target ring finger protein 145 (RNF145). RNF145 expressed at a high level in OSCC cells and circZDBF2 facilitated RNF145 transcription by recruiting the transcription factor CCAAT enhancer binding protein beta (CEBPB). Moreover, RNF145 activated NFκB (nuclear factor kappa B) signaling pathway and regulated IL-8 (C-X-C motif chemokine ligand 8) transcription. CONCLUSION: CircZDBF2 up-regulated RNF145 expression by sponging miR-362-5p and miR-500b-5p and recruiting CEBPB, thereby promoting OSCC progression via NFκB signaling pathway. The findings recommend circZDBF2 as a probable therapeutic target for OSCC.

Effect of Prepregnancy Lymphocyte Active Immunotherapy on Unexplained Recurrent Miscarriage, Pregnancy Success Rate, and Maternal-Infant Outcome.

OBJECTIVE: To evaluate the effect of prepregnancy lymphocyte active immunotherapy on unexplained recurrent miscarriage, pregnancy success rate, and maternal-infant outcome. METHODS: A total of 124 patients with recurrent miscarriage admitted to our hospital from January 2018 to December 2020 were selected as the research objects and divided into the experimental group and the control group according to the random number table method, with 62 patients in each group. The experimental group was treated with lymphocyte active immunotherapy, and the control group was given conventional treatment. The pregnancy success rate, estrogen indexes, hemorheology indexes, and psychological state of the two groups were compared. RESULTS: The experimental group garnered a notably higher pregnancy success rate and a prominently lower miscarriage rate than the control group (P < 0.05). Better results of self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were observed in the experimental group, as compared to the control group (P < 0.05). The experimental group yielded more desirable results in terms of treatment satisfaction, estrogen indexes, and hemorheology indexes in comparison with the control group (P < 0.05). CONCLUSION: The use of lymphocyte active immunotherapy for patients with unexplained recurrent miscarriage can significantly increase the pregnancy success rate, optimize the maternal-infant outcome, drive down the miscarriage rate, and ameliorate the patient's estrogen levels and hemorheology indicators, which is worthy of promotion and application in clinical practice.

[Retracted] MicroRNA-200c inhibits the metastasis of non-small cell lung cancer cells by targeting ZEB2, an epithelial-mesenchymal transition regulator.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell Transwell assay data in the article (featured in Figs. 2C and 4C) were strikingly similar to data appearing in different form in other articles by different authors at different research institutions, which were already under consideration for publication or had already been published elsewhere at the time of the present article's submission [C. Lai et al, 'MicroRNA­133a inhibits proliferation and invasion, and induces apoptosis in gastric carcinoma cells via targeting fascin actin­bundling protein 1', Mol Med Rep 12: 1473­1478, 2015; and Y. Shi et al, 'MicroRNA­204 inhibits proliferation, migration, invasion and epithelial­mesenchymal transition in osteosarcoma cells via targeting Sirtuin 1', Oncol Rep 34: 399­406, 2015]. Owing to the fact that the contentious data in the above article had already appeared in different form in other articles prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors did not reply to indicate whether or not they agreed with the retraction of the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 13: 3349-3355, 2016; DOI: 10.3892/mmr.2016.4901].

Cadmium isotope fractionation during Cd-calcite coprecipitation: Insight from batch experiment.

Cadmium (Cd) calcite coprecipitation experiments were conducted to constrain the possible Cd isotope fractionation mechanism under different conditions. The changes in Cd/Ca molar ratio, HCO3- concentration, addition of Mg2+, Na2EDTA, or ionic strength (INaNO3) did not affect the composition of the precipitation but resulted in substantial change in mineral morphology. Cd exhibited an apparent isotope fractionation in the process of coprecipitation with calcite, and the fractional coefficient αCaCO3-Cd(aq) was less than one, indicating that the solution is preferentially enriched in heavy isotopes. The Cd mainly existed in the form of Cd(H2O)62+ in the solution before the reaction and was dominated by Cd(NO3)2, CdNO3+, Cd(EDTA)2- at the end of the experiments. The different isotopic ratios of Cd between the liquid phase and the solid phase can be explained by changes in Cd speciation which have different bond lengths of CdO. Expect for the experiments with Na2EDTA and high ionic strength, the measured isotope ratios under different conditions plotted around the theoretical Rayleigh fractionation curve. This demonstrates that Cd isotopes almost reach equilibrium with Cd-calcite coprecipitation under the different experiment conditions and the Cd isotope fractionation mechanism is closely related to the thermodynamic isotope fractionation. In the experiment with Na2EDTA and high ionic strength, the formation of Cd(EDTA)2- and ion occlusion at surface sites inhibit Cd2+ entering the calcite and the isotopes of the solid and liquid phases do not reach equilibrium. As the result, obtained experiment data shift from the Rayleigh fractionation curve indicating the Cd isotope fractionation mechanism is closely related to the kinetic isotope effect. In general, the study results indicate that the Cd/Ca molar ratio, ionic strength, HCO3-, Na2EDTA, and Mg2+ concentrations of the solution can cause Cd isotope fractionation in different degrees during Cd-calcite coprecipitation. Cd isotope ratios might potentially provide important information on Cd mobilization and transportation in groundwater environment.

Mechanistic insights into iodine enrichment in groundwater during the transformation of iron minerals in aquifer sediments.

Long-term intake of groundwater with elevated iodine concentration can cause thyroid dysfunction in humans; however, little is known on the mechanisms controlling the fate of iodine in groundwater systems. In this study, the groundwater and aquifer sediment samples from the Datong basin, a geologic iodine-affected area, were collected to perform the batch incubation experiments to understand the release and enrichment of iodine in groundwater systems. The results showed that the groundwater from the deep confined aquifer had a total iodine concentration of 473 µg/L, higher than that of shallow groundwater, and iodide is the dominant species of iodine. The deep confined aquifer was characterized by the reducing conditions. Meanwhile, a higher ratio of Fe(II) to total Fe was observed in bulk deep aquifer sediments (59%) in comparison with that of shallow sediments (33%). The results of batch incubation experiments showed that during the reductive transformation of Fe minerals in shallow aquifer sediments, iodide concentration in solution was gradually increasing from 24.7 to 101.5 µg/L after 10 days. It suggests that the transformation of Fe minerals in aquifer sediments acts as a diver causing the release of iodine from sediment into groundwater, which was further supported by the features Fe K-edge EXAFS before and after the batch experiments. Moreover, the changes in iodine species from iodate or organic iodine into iodide during the release further promotes the release of sediment iodine, which was supported by the developed geochemical models. The prevalence of reducing condition in deep aquifer favors the enrichment of released iodide. This study provides new insights into the mechanisms of iodide enrichment observed in deep confined aquifer.

Iron isotope evidence for arsenic mobilization in shallow multi-level alluvial aquifers of Jianghan Plain, central China.

Intake of groundwater with arsenic (As) concentrations exceeding the World Health Organization standard of 10 µg L-1 adversely impacts over 100 million people worldwide. Geogenic As contaminated groundwater within central Yangtze River Basin has recently been reported, but the variations within different depths of aquifers are not commonly observed and the processes controlling As variations have yet to be resolved. Here we report the significant As variations within two different depths (10 m and 25 m) of shallow multi-level alluvial aquifers at Jianghan Plain, a floodplain in the central Yangtze River Basin, which is also a recently discovered geogenic As affected area with cases of waterborne arsenicosis. The multi-year monitoring of aquifer chemistry results show that the As concentrations increase with the Fe(II) concentrations when As contents are relatively lower (<200 µg L-1) in upper phreatic aquitard (at 10 m depth), while decrease with Fe(II) concentrations when As contents are much greater in lower confined aquifer (at 25 m depth), and the highest is up to 1070 µg L-1. Iron isotope analysis were conducive to characterize Fe cycling in the aquifers and thus illustrate geochemical processes controlling As mobilization of shallow groundwaters. Results showed that groundwater is generally enriched in isotopically light Fe with δ56Fe values between - 1.60‰ and + 0.06‰ (median - 0.55‰). In the upper phreatic aquitard, microbial reductive dissolution of As-associated Fe(III) oxides, hydroxides and oxyhydroxides is the major process controlling As concentrations lower than 200 µg L-1. The reduction process could lead to the increasing As concentrations with the gradually increasing δ56Fe values, and a positive correlation between Fe and Î´56Fe, and between dissolved As and δ56Fe values is observed, respectively. In strongly reducing conditions as the lower confined aquifer, jointly microbial reduction of sulfate promotes the As mobilization through HS- abiotic reduction of Fe(III) minerals, resulting in As concentrations greater than 200 µg L-1. These findings could provide new insights for differentiating the major factors controlling As mobilization at different depths of aquifers, and provide better water managements for similar geogenic As-affected shallow alluvial aquifers.

Arsenic immobilization by in-situ iron coating for managed aquifer rehabilitation.

A long-lasting challenge in eliminating the worldwide impact of geogenic arsenic (As)-contaminated groundwater is the development of efficient, in-situ treatment technologies that are applicable in decentralized and rural areas. Here we present a managed aquifer rehabilitation (MAR) approach based on the in-situ creation of Fe-oxide scavengers for remediating As-contaminated groundwater. The Fe-oxide coatings on sediment surfaces were generated via periodic injection of Fe2+ and ClO- solutions into an As-affected sandy aquifer at the Datong Basin, northern China for 25 days. This treatment prompted the buildup of weakly alkaline/circumneutral and oxidizing conditions to enhance As(III) oxidation in the target aquifer. Dissolved As concentrations decreased from the initial average 78.0 to 9.8 µg/L over the 25-d amendment. Sediment imaging by scanning electron microscope-X-ray energy dispersive spectroscopy confirms the deposition of Fe-rich precipitates on sediment surfaces with the simultaneous retention of As, and high density electrical tomography suggests the occurrence of such a process throughout the target zone. Further X-ray diffraction analysis and sequential chemical extraction reveal that the neo-formed Fe minerals comprised both poorly crystalline (e.g., ferrihydrite) and better crystalline (e.g., goethite) Fe oxides. The process-based reactive-transport modeling for the variations of As species in the treated groundwater supports that the new Fe-oxide minerals, most probably goethite, acted as efficient removers of aqueous As. The low As level of ∼10 µg/L was maintained during the following 215-d monitoring, demonstrating the long effectiveness of the MAR approach. This study highlights the feasibility of As immobilization by manipulating in-situ Fe-oxide coating on sandy sediments at the pilot scale. The MAR technology may be applicable for As-affected aquifers with controlled oxidizing conditions in the Datong Basin and likely other high-As regions with similar hydrogeochemical settings.

Mechanism of PM2.5-induced human bronchial epithelial cell toxicity in central China.

Exposure to PM2.5 has been linked to respiratory disorders, yet knowledge of the molecular mechanism is limited. Here, PM2.5 was monitored and collected in central China, and its cytotoxicity mechanism on human bronchial epithelial cells (BEAS-2B) was investigated. With the average concentration of 109 ±â€¯69 µg/m3, PM2.5 was rich in heavy metals and organic pollutants. After exposure to PM2.5, the viability of BEAS-2B cells decreased, where 510 dysregulated genes were predicted to induce necroptosis via inhibiting ATP synthesis through the oxidative phosphorylation signaling pathway. Cellular experiments demonstrated that the content of ATP was downregulated, while the expression of RIP3, a necroptosis indicator, was upregulated. Besides, four enzymes in charge of ATP synthesis were downregulated, including ATP5F, NDUF, COX7A, and UQCR, while two genes of RELA and CAPN1 responsible for necroptosis were upregulated. Furthermore, N-acetylcysteine was applied as an enhancer for ATP synthesis, which reversed the downregulation of ATP5F, NDUF, and COX7A, and consequently alleviated the elevation of RELA, CAPN1, and RIP3. In conclusion, PM2.5 exposure downregulates ATP5F, NDUF, COX7A, and UQCR, and that inhibits ATP synthesis via the oxidative phosphorylation signaling pathway, which subsequently upregulates RELA and CAPN1 and ultimately leads to necroptosis of BEAS-2B cells.

Comprehensive characterization of endometrial competing endogenous RNA network in infertile women of childbearing age.

Endometriosis is widely associated with infertility in women of childbearing age, for which there have been no effective treatments. Recent studies suggest that the dysregulation of RNAs contributes to the pathogenesis of endometriosis, so we conduct the case-control genetic analysis to characterize the expression and interaction of different subtypes of RNAs in infertile women with endometriosis. The ectopic and eutopic endometrium of patients undergoing infertility treatment were collected and subjected to high throughput sequencing, and bioinformatics analysis was conducted to construct the competing endogenous RNA (ceRNA) network. As a result, the RNA interactive network was constructed in endometriosis, and a set of mRNAs such as cyclin-dependent kinase 1 (CDK1) and proliferating cell nuclear antigen (PCNA) along with their corresponding miRNAs and lncRNAs were found to promote the growth and death of endometrial stromal cells, which was essential for the pathogenesis of endometriosis. These data suggest that RNA crosstalk is a crucial segment in the development of endometriosis, where CDK1 and PCNA may serve as emerging targets for the treatment of endometriosis-related infertility in women of childbearing age.

Eriodictyol ameliorates lipopolysaccharide-induced acute lung injury by suppressing the inflammatory COX-2/NLRP3/NF-κB pathway in mice.

The purpose of this paper is to observe the protective action and its effective mechanism of eriodictyol on lipopolysaccharide (LPS)-induced acute lung injury (ALI). In this study, our results indicated that eriodictyol could dramatically suppress the inflammatory mediators, including interleukin-6 (IL-6), IL-1ß, prostaglandin E2, and tumor necrosis factor-α in bronchoalveolar lavage fluid of LPS-challenged mice. Eriodictyol also alleviated the wet/dry ratio and improved pathological changes of the lung. In addition, eriodictyol significantly decreased myeloperoxidase activity and malondialdehyde content as well as increased superoxide dismutase activity. Moreover, eriodictyol inhibited the COX-2/NLRP3/NF-κB signaling pathway in the lung tissues of ALI mice. In conclusion, our observations validated that eriodictyol processed the protective effects on ALI mice, which was related to the regulation of the COX-2/NLRP3/NF-κB signaling pathway.

Crosstalk between let-7a-5p and BCL-xL in the Initiation of Toxic Autophagy in Lung Cancer.

Autophagy is essential for cellular metabolism and plays pivotal roles in carcinogenesis, while excessive autophagy induces toxicity and cell death. Our previous studies have suggested that let-7a-5p/BCL-xL might regulate autophagy in lung cancer, but the regulatory mechanism is unclear. The central goal of the study was to figure out the role of let-7a-5p/BCL-xL in the initiation of autophagy and its effect on the migration, invasion, and proliferation of A549 cells as well as its therapeutic potential in lung cancer. Based on the genome-wide expression profiles of lung cancer, BCL-xL and let-7a-5p were found to be dysregulated and negatively correlated in lung adenocarcinoma, which was associated with the survival of lung cancer. The crosstalk between BCL-xL and let-7a-5p was then investigated using dual-luciferase reporter assay, and it was found to suppress the migration and invasion of A549 cells. Further, we found that the crosstalk between BCL-xL and let-7a-5p could lead to toxic autophagy and cell death through activating the PI3K-signaling pathway, which was independent of apoptosis or pyroptosis. These findings indicate that let-7a-5p is a sensitive initiator for toxic autophagy in A549 lung cancer cells and is an appealing target for lung cancer therapy.