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We conducted a crossover study employing air cleaner intervention among 125 schoolchildren aged 9-12 years in a boarding school in Beijing, China. The PM concentrations were monitored, and 27 biomarkers were analyzed. We used the linear mixed-effects model to evaluate the association of intervention/time-weighted PM concentrations with biomarkers. The outcomes showed that air cleaner intervention was associated with FeNO, exhaled breath condensate (EBC) IL-1β, and IL-6, which decreased by 12.57%, 10.83%, and 4.33%, respectively. Similar results were observed in the associations with PMs. Lag 1 day PMs had the strongest relationship with biomarkers, and significant changes were observed in biomarkers such as FEV1, FeNO, EBC 8-iso, and MCP-1. Boys showed higher percentage changes than girls, and the related biomarkers were FeNO, EBC 4-HNE, IL-1β, IL-6, and MCP-1. The results showed that biomarkers such as FeNO, EBC IL-6, MCP-1, and 4-HNE could sensitively reflect the early abnormal response of the respiratory system under short-term PM exposure among healthy schoolchildren and indicated that (1) air cleaners exert a protective effect on children's respiratory system. (2) PM had lag and cumulative effect, lag 1 day had the greatest effect. (3) The boys were more sensitive than the girls.

Burn injury has posed devastating burdens on the public health due to its inevitable damage to the skin structure resulting in the increased risk of infection. Therefore, it is highly demanding to develop efficacious antibacterial wound-healing dressing. Despite the favourable wound-healing activities, the curative efficacy of phytochemical compounds of quercetin (Qe) and its derivatives is limited by their poor water solubility. Here, we have fabricated a novel electrospun nanofiber membrane (ENM) consisting of polycaprolactone (PCL), chitosan oligosaccharides (COS), and Qe/Rutin (Ru) as the potential bioactive dressing for wound healing. The incorporation of chitosan oligosaccharides (COSs) in the PCL scaffold at the optimized molar ratio not only contributed to the improved hydrophilicity and water absorption performance of the ENM but effectively increased the specific surface area of the formed nanofibers. In particular, the antioxidant and antibacterial activities of the Qe/rutin-loaded nanofiber membranes were tested, which revealed that the PCL-COS-Qe membrane exhibited superior performance among all nanofiber membranes. Therefore, the developed PCL-COS-Qe/Ru nanofiber membranes hold enormous potential as healthcare products, such as wound dressings for burn injuries.

Nowadays, pathogenic infection has posed a severe threat to the public health and environmental sanitation, urging a continuous search of efficacious and safe bactericidal agents of various formulated forms. Here, a facile one-pot hydrothermal preparation of mesoporous silica nanoparticles using ultrasonication-assisted nanoemulsion of α-Linolenic acid (α-LA) as template was developed. The formed silica mesocomposite at water/fatty-acid surface provides an easy yet green synthesis route, which can be generalized for the further encapsulation of hydrophobic drugs such as antimycobacterial Rifampicin (RIF). The obtained α-LA nanoemulsion-templated silica nanoparticles (LNS NPs), with a weight content of ∼17% α-LA in the composite, showed apparent antibacterial effect against Staphylococcus aureus (S. aureus). By comparison, the removal of α-LA from the silica nanoparticles (LNS-1 NPs) resulted in the composite of enlarged pore size with negligible bactericidal activities. Notably, the Isoniazide (INH) and Rifampicin (RIF)-encapsulated LNS NPs exhibited outstanding antimycobacterial activity against both drug-sensitive and drug-resistant Mycobacterium tuberculosis (M. tuberculosis). The obtained highly biocompatible, biosafe and low-energy consumptive α-LA-contained mesostructured silica-based bactericide holds promising therapeutic potentials to tackle the emerging drug-resistant infectious microbes.

A straightforward synthesis of alkynylthioethers via an amino-assisted and visible-light-promoted coupling reaction of bromoalkynes with 2,2′-diaminodiaryldisulfides has been developed. The reaction can be accomplished in the absence of transition metals, photocatalysts and additives, providing a wide variety of alkynylthioethers in good yields. While switching bromoalkynes to aliphatic ketones, a visible-light-induced cascade cyclization is established to afford dihydrobenzothiazoles using pyrylium salt as an effective photocatalyst.

Background: Increasing evidence shows that GSDME is involved in tumor chemotherapy. Lobaplatin is an important chemotherapy drug for the treatment of cervical cancer. However, the exact mechanism of lobaplatin in the treatment of cervical cancer remains unclear. Objective: In this study, whether GSDME is a new mechanism of lobaplatin in the treatment of cervical cancer has been explored. Methods: Cell pyroptosis was measured by Cell Counting Kit-8 and flow cytometry analyses. Western blot analysis was used to check proteins expression. Results: The cell viability was significantly decreased by lobaplatin treatment. Compared with the control group, the percentage of pyroptosis (PI and Annexin-V double-positive cells) increased after lobaplatin treatment. In addition, lobaplatin induced caspase-3 activation and GSDME cleavage. z-DEVD, a specific inhibitor of caspase-3, reduced lobaplatin-mediated GSDME cleavage and concurrently inhibited pyroptosis. More importantly, GSDME deficiency obviously reduced lobaplatin-induced pyroptosis. Conclusion: These data demonstrate that caspase-3/GSDME axis contributed to the lobaplatin-mediated pyroptosis in cervical cancer cells. This finding indicates that GSDME-mediated pyroptosis is a new mechanism for lobaplatin to kill tumor cells and suggests that the caspase-3/GSDME pathway offers new insights into cancer chemotherapy.

Critical cytotoxicity evaluation of pharmaceuticals is necessary for the clinical practice of chemotherapy. To quantitatively evaluate cell viability, currently there are two main types of sensitive methods including real-time cell analysis (RTCA) and CCK-8 assay, in which RTCA records electrochemical signal changes around an incubated cell, whereas CCK-8 is based on the colorimetric method. Despite the different detection principles adopted for the cytotoxicity assessment, the comparison of the two methods in terms of the application scope is lacking. In this study, comparison studies were conducted between the RTCA and CCK-8 assays using anticancer drugs including doxorubicin hydrochloride, curcumin, irinotecan (CPT-11), taxol, and oxaliplatin, which are classified into two groups of drug molecules in the absence and presence of additives. The cytotoxicity evaluation of these drugs on cancer cells revealed that the physicochemical properties of drug formulations such as optical and electrochemical properties are closely linked with the readout of cytotoxic methods. The experimental results suggested that the preselection of cytotoxic assay is critical for the quantitative measurement of cytotoxicity of anticancer drugs, which is of clinical importance for their therapeutic usage.

Vulvovaginal candidiasis (VVC), a major gynecological disease with high recurrence rate, increases the risk of abortion, intrauterine infection, premature rupture of membranes, and premature birth in pregnancy. However, the exact pathogenesis of this disease has yet to be elucidated. To facilitate understanding of the pathogenesis of VVC in pregnancy, this study sought to establish an animal model of vaginal infection with Candida albicans in pregnant mice. Female mice were mated with male mice, and female mice were infected with C. albicans at E4.5 (embryonic day 4.5). The weight and abortion rate of pregnant mice at E0.5, E4.5, E8.5, E11.5, and E18.5 were recorded, respectively, as well as the weights of fetus and placenta on E18.5. Fetal weight at E18.5 and the weight growth rate in the experimental mice was lower than those in the control mice, but the placenta weight at E18.5 and the abortion rate in the experimental mice were increased with those of the control mice. Hematoxylin-eosin (HE) staining, Gomori-Grocott staining and vaginal lavage culturing were conducted to verify that the experimental mice were infected with C. albicans. Differentially expressed gene IL-15 was screened out by polymerase chain reaction (PCR) array between the two groups. Enzyme-linked immunosorbent assay (ELISA) showed that IL-15 expression in plasma of the mice was decreased in the experimental group compared with the control group. RT-qPCR confirmed that IL-15 mRNA expression was increased in placental tissues, while mRNA expression of IL-15R/JAK1-JAK3/PI3K/PDK1/AKT/P70S6K-mTOR was decreased in placental tissues. In conclusion, this study demonstrated that VVC in BALB/c pregnant mice led to a series of adverse pregnancy outcomes that were related to changes in IL-15 and its downstream signaling pathways, which may indicate a potential therapy for VVC during pregnancy in humans.

Background: The protective effect of air purifiers on the respiratory system of healthy children remains unclear so far. Method: We designed an air purifier intervention crossover study among 125 schoolchildren aged 9–12 years in a boarding school in Beijing, China. The indoor and outdoor PM10, PM2.5, and PM1 concentrations were monitored, and a total of 30 indices, including respiratory symptoms, pulmonary functions, inflammation, and oxidative stress indicators, were analyzed. We used the logistic mixed-effects model and the linear mixed-effects model to evaluate the correlation between exposure (intervention and time-weighted PM concentration) and effects (indicators). Findings: The findings showed that the air purifier intervention was associated with a 13.29% decrease in runny nose, 11.05% decrease in FeNO, 12.03% decrease in EBC IL-1β, and 4.2% decrease in IL-6. The patterns of associations with each 10 µg/m3 decrease in the PM10, PM2.5, and PM1 concentrations were consistent with those for filter intervention. Moreover, lower PM2.5 and PM1 were associated with lower EBC MCP-1, 5.47% and 13.56%, respectively. The pulmonary function indices were negatively associated with the intervention and PM. Interpretation: We screened out some sensitive indices (FeNO, IL-6, IL-1β, MCP-1) related to respiratory symptoms and inflammation, which could reflect the early abnormal response of the respiratory system under short-term PM exposure. Our findings suggested that air purifiers have a protective effect on children’s respiratory system. Funding: This work was supported by the National research program for key issues in air pollution control, China (Grant No. DQGG0405). Declaration of Interest: None to declare. Ethical Approval: The study was approved by the Ethics Review Committee of National Institute of Environmental Health, Chinese Center for Disease Control and Prevention (No. 201803) and the Biomedical Ethics Committee of Peking University (No. IRB00001052-18089). Parents and schoolchildren were informed about the study beforehand, and all the participants and their parents signed the informed consent.

The aim of our study was to investigate microRNA (miRNA) expression profiles in CD44In this study, we enriched CD44We found that CD44Our data suggest that miRNAs play important roles in regulating the stem cell-like properties of CD44

Heading aims LncRNA HOXB-AS3 is proved as an oncogene in tumors. Herein, we determine the function and mechanism of HOXB-AS3 in epithelial ovarian cancer (EOC) cells. Materials and methods Chi-square test, Kaplan-Meier (KM) analysis and Cox regression analysis were used to analyze the clinicopathological features of HOXB-AS3 in EOC patients. CCK8, transwell and wound healing assay were used to test the function of HOXB-AS3. Luciferase reporter assay, western blot and glycolysis rate assay were used for further mechanistic studies. Key findings HOXB-AS3 was abundantly expressed in EOC tissues, and higher levels of HOXB-AS3 in EOC patients were significantly associated with disease status and overall survival status. EOC patients with high levels of HOXB-AS3 had strikingly shorter disease-free survival (DFS) and overall survival (OS) times than those with low levels. HOXB-AS3 also might as an independent prognostic factor. Further study revealed knockdown of HOXB-AS3 significantly inhibited the proliferation, invasion and migration of EOC cells. Mechanistic investigations suggested that knockdown of HOXB-AS3 could decrease lactate dehydrogenase A (LDHA) expression and the extracellular acidification rate (ECAR) by sponging miR-378a-3p. Significance To our knowledge, this is the first study to suggest that HOXB-AS3 could crosstalk with miRNA in the cytoplasm and alter glycolysis in cancer cells. Our results improve our understanding of the mechanism of HOXB-AS3 and suggest that HOXB-AS3 can act as a predictor of OS and a target for EOC therapies.

A coupling of bromoalkynes with secondary phosphine oxides was developed for the synthesis of alkynylphosphine oxides. This transformation was accomplished under additive-free conditions in acetic anhydride (Ac2O). The reaction could be carried out under mild conditions, and a wide range of secondary phosphine oxides were obtained in good yields.

Previous studies have shown that retinoblastoma binding protein 6 (RBBP6) was overexpressed in malignant tumors and was correlated with poorer prognosis in various cancers. However, its role in cervical carcinoma has not been elucidated. This study was to investigate the relationship between RBBP6 and cervical carcinoma. Cervical carcinoma cell lines SiHa and C33a were used to assess the effect of RBBP6 on cell viability, migration, and proliferation. RBBP6 mRNA and protein levels in cervical cancer tissues increased at least three times as that in the adjacent non-cancerous tissues. Overexpression of RBBP6 in SiHa and C33a cell lines resulted in increased phosphorylated c-Jun NH2-terminal kinase (p-JNK) as well as increased cell viability, migration, and proliferation. Moreover, this effect was suppressed by specific JNK inhibitor SP600125. RBBP6 might potentiate cervical carcinoma cell viability, migration and proliferation through JNK signaling pathway. RBBP6 and JNK inhibitor may be beneficial as a novel preventive and therapeutic target for cervical cancer.

Preeclampsia (PE), a life-threatening, complicated pregnancy-associated disease, has recently become a research focus in obstetrics. However, the peptidome of the amniotic fluid in PE patients has rarely been investigated. The present study used peptidomic profiling to perform a comparative analysis of human amniotic fluid between normal and PE pregnancies. Centrifugal ultrafiltration and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was combined with isotopomeric dimethyl labels to gain a deeper understanding of the role of proteins and the peptidome in the onset of PE. Following ultrafiltration and LC-MS/MS, 352 peptides were identified. Of these, 23 peptides were observed to be significantly differentially expressed (6 downregulated and 17 upregulated; P

Recurrent spontaneous abortion (RSA) is an unknown aetiology common disease troubled women all over the world. Recent studies of circular RNAs (circRNAs) in gynecology and obstetrics area have sprung up. Our purpose in this study was to investigate the expression of circRNAs in chorionic villi from patients with RSA versus corresponding healthy gravidas, and to infer the potential role of these circRNAs in RSA occurrence. We selected 35 pairs of RSA patients and healthy control subjects, and analyzed the aberrant circRNA expression in three pairs of villi samples from each group using circRNA microarray. Altogether, including 335 up-regulated and 259 down-regulated circRNAs, 594 aberrant expressed circRNAs (FC ≥ 2.0, P ≤ 0.05) were found. Considering the raw content of each circRNAs, fold change differences and the restriction of the divergent primers, four down-regulated circRNAs (hsa_circRNA_104948, 104547, 101319 and 104938) and four up-regulated (hsa_circRNA_102116, 100709, 102424 and 103102) were selected as validation genes, using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Paired t-test and receiver operating characteristic (ROC) curves were also established. The result of content verification was accordant exactly with the microarray chip outcome (P ≤ 0.05 in all validation circRNAs). The area under the ROC curves (AUCs) of these eight circRNAs were all greater than 0.5. Further function analysis of circRNAs in RSA patients was performed by paper comparison. Taken together, aberrant villi circRNA expression in RSA played a vital role in its nosogenesis possibly via miRNA sponge function of circRNAs. Deeper analysis of the detailed mechanisms will be worthwhile.

Recent studies suggest that long non-coding RNAs (lncRNAs) play crucial roles in many types of human malignant cancers. However, the function of lncRNAs in benign tumors remains poorly understood. In the present study, to explored the potential roles of lncRNAs in benign epithelial ovarian cysts (BEOCs) which commonly occur in young women and possess malignant potential, we described the expression profile of the lncRNAs between BEOC and normal ovarian tissues using lncRNA microarray techniques. The results showed that 1,325 transcripts of lncRNAs (1,014 upregulated and 311 downregulated) were differentially expressed in the BEOCs compared with the normal controls [absolute fold-change ≥2, false discovery rate (FDR)

Human milk has always been considered an ideal source of elemental nutrients to both preterm and full term infants in order to optimally develop the infant's tissues and organs. Recently, hundreds of endogenous milk peptides were identified in human milk. These peptides exhibited angiotensin-converting enzyme inhibition, immunomodulation, or antimicrobial activity. Here, we report the antimicrobial activity and mechanism of a novel type of human antimicrobial peptide (AMP), termed PDC213 (peptide derived from β-Casein 213-226 aa). PDC213 is an endogenous peptide and is present at higher levels in preterm milk than in full term milk. The inhibitory concentration curve and disk diffusion tests showed that PDC213 had obvious antimicrobial against S. aureus and Y. enterocolitica, the common nosocomial pathogens in neonatal intensive care units (NICUs). Fluorescent dye methods, electron microscopy experiments and DNA-binding activity assays further indicated that PDC213 can permeabilize bacterial membranes and cell walls rather than bind intracellular DNA to kill bacteria. Together, our results suggest that PDC213 is a novel type of AMP that warrants further investigation.

The chemoselectivity of visible-light-induced coupling reactions of bromoalkynes with alcohols can be controlled by simple changes to the reaction atmosphere (N2 or O2). A N2 atmosphere favours propargyl alcohols via a direct C-C coupling process, whereas an O2 atmosphere results in the generation of α-ketoesters through the oxidative C[triple bond, length as m-dash]C/C-O coupling pathway.

Background/Aims: Benzotriazole (BTR) and its derivatives, such as intermediates and UV stabilizers, are important man-made organic chemicals found in everyday life that have been recently identified as environmental toxins and a threat to female reproductive health. Previous studies have shown that BTR could act as a carcinogen by mimicking estrogen. Environmental estrogen mimics could promote the initiation and development of female cancers, such as endometrial carcinoma, a type of estrogenic-sensitive malignancy. However, there is little information on the relationship between BTR and endometrial carcinoma. In this study, we aimed to demonstrate the biological function of BTR in endometrial carcinoma and explored the underlying mechanism. Methods: The CCK-8 assay was performed to detect cell viability; transwell-filter assay was used to assess cell invasion; gene microarray analysis was employed to determine gene expression patterns in response to BTR treatment; western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were carried out to detect the expression levels of BTR-related genes. Results: Our data showed that BTR could induce the invasion and migration of endometrial carcinoma cells (Ishikawa and HEC-1-B). In addition, BTR increased the expression level of CTBP1, which could enhance the epithelial-mesenchymal transition (EMT) in cancer cells. Moreover, CTBP1 silencing reversed the effect of BTR on EMT progression in endometrial carcinoma cells. Conclusion: This study indicates that BTR could act as a carcinogen to promote the development of endometrial carcinoma mainly through CTBP1-mediated EMT, which deserves more attention.

We developed a modified local lymph node assay based on ATP (LLNA:DA), termed the Two-Stage LLNA:DA, to further reduce the animal numbers in the identification of sensitizers. In the Two-Stage LLNA:DA procedure, 13 chemicals ranging from non-sensitizers to extreme sensitizers were selected. The first stage used reduced LLNA:DA (rLLNA:DA) to screen out sensitive chemicals. The second stage used LLNA:DA based on OECD 442 (A) to classify those potential sensitizers screened out in the first stage. In the first stage, the SIs of the methyl methacrylate, salicylic acid, methyl salicylate, ethyl salicylate, isopropanol and propanediol were below 1.8 and need not to be tested in the second step. Others continued to be tested by LLNA:DA. In the second stage, sodium lauryl sulphate and xylene were classified as weak sensitizers. a-hexyl cinnamic aldehyde and eugenol were moderate sensitizers. Benzalkonium chloride and glyoxal were strong sensitizers, and phthalic anhydride was an extreme sensitizer. The 9/9, 11/12, 10/11, and 8/13 (positive or negative only) categories of the Two-Stage LLNA:DA were consistent with those from the other methods (LLNA, LLNA:DA, GPMT/BT and HMT/HPTA), suggesting that Two-Stage LLNA:DA have a high coincidence rate with reported data. In conclusion, The Two-Stage LLNA:DA is in line with the "3R" rules, and can be a modification of LLNA:DA but needs more study.

Endometrial carcinoma (EC) is the most common malignancy in women. Dispite its prevalence, the prognosis of endometrial carcinoma still relies on conventional histological type, grade and invasion information. Its morbidity is still increasing and the outcome is very poor. To the best of our knowledge, hormonal imbalance and/or molecular genetic alterations are the main cause of EC. However, the alterations of lncRNAs which accounts for approximately 4/5 of human transcripts are still poorly understood. In the present study, using the RiboArray™ Custom Array, we studied the expression profiles of lncRNA in EC as compared to normal endometrium (NE) to find potential core lncRNAs for the diagnosis of EC. We found the potential core lncRNA by GO, KEGG, lncRNA and mRNA co-expression network. The potential functional lncRNAs were further detected by qPCR to validate the microarray results. A total of 172 lncRNAs and 188 mRNAs were found to be differentially expressed between type Ⅰ EC and the NE samples (fold change >1.5). qPCR validation showed good consistency with the microarray data. GO, pathway analysis, the lncRNA and mRNA co-expression network as well as the TCGA data revealed that 6 lncRNAs (KIAA0087, RP11-501O2, FAM212B-AS1, LOC102723552, RP11-140I24 and RP11-600K151) may be the core regulators of endometrial carcinogenesis. The potential core lncRNAs revealed by the mRNA and lncRNA co-expression network might be helpful to explore potential early diagnostic and therapeutic targets for EC.