One-pot co-crystallized hexanal-loaded ZIF-8/quaternized chitosan film for temperature-responsive ethylene inhibition and climacteric fruit preservation.

Controlling ethylene production and microbial infection are key factors to prolong the shelf life of climacteric fruit. Herein, a nanocomposite film, hexanal-loaded ZIF-8/CS (HZCF) with "nano-barrier" structure, was developed by a one-pot co-crystallized of ZIF-8 in situ growth on quaternized chitosan (CS) and encapsulation of hexanal into ZIF-8 via microporous adsorption. The resultant film realized the temperature responsive release of hexanal via the steric hindrance and hierarchical pore structure as "nano-barrier", which can inhibit ethylene production in climacteric fruit on demand. Based on this, the maximum ethylene inhibition rate of HZCF was up to 52.6 %. Meanwhile, the film exhibits excellent antibacterial, mechanical, UV resistance and water retention properties, by virtue of the functional synergy between ZIF-8 and CS. Contributed to the multifunctional features, HZCF prolonged the shelf life of banana and mango for at least 16 days, which is 8 days longer than that of control fruit. More strikingly, HZCF is washable and biodegradable, which is expected to replace non-degradable plastic film. Thus, this study provides a convenient novel approach to simplify the encapsulation of active molecule on metal-organic frameworks (MOFs), develops a packaging material for high-efficient freshness preservation, and helps to alleviate the survival crisis caused by food waste.

Multi-omics analyses of glucose metabolic reprogramming in colorectal cancer.

Background: Glucose metabolic reprogramming (GMR) is a cardinal feature of carcinogenesis and metastasis. However, the underlying mechanisms have not been fully elucidated. The aim of this study was to profile the metabolic signature of primary tumor and circulating tumor cells from metastatic colorectal cancer (mCRC) patients using integrated omics analysis. Methods: PET-CT imaging, serum metabolomics, genomics and proteomics data of 325 high 18F-fluorinated deoxyglucose (FDGhigh) mCRC patients were analyzed. The para-tumor, primary tumor and liver metastatic tissues of mCRC patients were used for proteomics analysis. Results: The glucose uptake in tumor tissues as per the PET/CT images was correlated to serum levels of glutamic-pyruvic transaminase (ALT), total bilirubin (TBIL), creatinine (CRE). Proteomics analysis indicated that several differentially expressed proteins were enriched in both GMR and epithelial-mesenchymal transition (EMT)-related pathways. Using a tissue-optimized proteomic workflow, we identified novel proteomic markers (e.g. CCND1, EPCAM, RPS6), a novel PCK1-CDK6-INSR protein axis, and a potential role for FOLR (FR) in GMR/EMT of CRC cells. Finally, CEA/blood glucose (CSR) was defined as a new index, which can be used to jointly diagnose liver metastasis of colorectal cancer. Conclusions: GMR in CRC cells is closely associated with the EMT pathway, and this network is a promising source of potential therapeutic targets.

Circulating neutrophil gelatinase-associated lipocalin and preeclampsia: a meta-analysis.

BACKGROUND: Previous studies evaluating the association between circulating neutrophil gelatinase-associated lipocalin (NGAL) and the risk of preeclampsia (PE) showed inconsistent results. A systematic review and meta-analysis was performed to summarize the relationship between circulating NGAL and PE. METHODS: Studies comparing the circulating NGAL between pregnant women with PE and controls with no PE were found by searching Medline, Web of Science, Cochrane's Library, and Embase. Pooling results was performed using a random-effects model incorporating heterogeneity. RESULTS: In the study, 1293 women with PE and 1773 healthy pregnant women were enrolled in 18 case-control studies, and the gestational age was matched between cases and controls. Pooled results showed that compared to controls, women with PE had a significantly higher blood level of NGAL (standardized mean difference [SMD]: 0.95, 95% confidence interval [CI]: 0.63-1.28, p < .001; I2 = 92%). Subgroup analyses showed consistent results in studies of NGAL measured at the first (SMD: 0.47, 95% CI: 0.15-0.80, p = .004), the second (SMD: 0.87, 95% CI: 0.55-1.19, p < .001), and the third trimester (SMD: 1.06, 95% CI: 0.63-1.24, p < .001) of pregnancy. In addition, women with mild (SMD: 0.78, 95% CI: 0.13-1.44, p = .02) and severe PE (SMD: 1.19, 95% CI: 0.40-1.97, p = .003) both had higher circulating NGAL as compared to controls. CONCLUSIONS: High circulating NGAL is associated with PE, which may be independent of the trimesters for blood sampling and the severity of PE.

Proteomics and liquid biopsy characterization of human EMT-related metastasis in colorectal cancer.

Tumor cells undergo epithelial-mesenchymal transition (EMT), however, there is a room of disagreement in role of EMT heterogeneity to colorectal cancer metastasis (mCRC) evolution. To uncover new EMT-related metastasis proteins and pathways, we addressed the EMT status in colorectal cancer liver metastasis patient-derived CTCs to identify proteins that promote their distant metastasis. And then, we performed a comparative proteomic analysis in matched pairs of primary tumor tissues, adjacent mucosa tissues and liver metastatic tissues. By integrative analysis we show that, unstable Epithelial/Mesenchymal (E/M)-type CTCs had the strongest liver metastases formation ability and the proportion of E/M-type CTCs correlated with distant metastases. Using an optimized proteomic workflow including data independent acquisition (DIA) and parallel reaction monitoring (PRM), we identified novel EMT-related protein cluster (GNG2, COL6A1, COL6A2, DCN, COL6A3, LAMB2, TNXB, CAVIN1) and well-described (ERBB2) core protein level changes in EMT-related metastasis progression, and the proteomic data indicate ERBB2, COL6A1 and CAVIN1 are promising EMT-related metastatic biomarker candidates. This study contributes to our understanding of the role that EMT plays in CRC metastasis and identifies heterogeneous EMT phenotypes as a key piece for tumor progression and prognosis. We further propose that therapies targeting this aggressive subset (E/M-type) of CTCs and related protein may be worthy of exploration as potential suppressors of metastatic evolution.

The Microstructure Transformations and Wear Properties of Nanostructured Bainite Steel with Different Si Content.

Nanostructured bainite (NB) bearing steel has excellent strength and ductility combinations, which can improve the fatigue life and wear resistance of bearing steel in harsh conditions. However, the phase transformations and the correlation between the microstructure and wear properties of NB bearing steel are still unclear. In this study, bearing steels with different Si contents (GCr15SiMo and GCr15Si1Mo) were prepared to have nano-bainitic structures, and their microstructure transformations and wear mechanisms were investigated. The results show that the Si element can inhibit the precipitation of carbides and can then promote the block-like retained austenite formation and refine the bainitic ferrite lamellar structure. The impact energy of GCr15Si1Mo is larger than that of GCr15SiMo because the nanostructured bainite and retained austenite are the main toughness phase in these steels. The wear results indicate that the steels which possess appropriate strength and toughness are helpful for improving wear resistance properties. Finally, the wear resistance performance of the GCr15Si1Mo austempered at 210 °C and GCr15SiMo austempered at 230 °C was good in this work.

Circular RNA circPBX3 promotes cisplatin resistance of ovarian cancer cells via interacting with IGF2BP2 to stabilize ATP7A mRNA expression.

Circular RNAs (circRNAs) are a class of non-coding RNAs with a unique covalently closed loop structure. Recent studies indicate that dysregulation of circRNAs acts a role in cancer progression and chemotherapy resistance via interacting with RNA-binding proteins (RBPs). Herein, we identified circPBX3 to be involved in cisplatin resistance of ovarian cancer. In our study, two cisplatin-resistant ovarian cancer cell lines were established, and transcriptome RNA-sequencing was performed and circPBX3 was identified as significantly upregulated circRNA in these cells. The characteristics of circPBX3 and potential function of circPBX3 were evaluated. We found that circPBX3 was upregulated in ovarian tumor tissues and cisplatin-resistant ovarian cancer cells. CircPBX3 overexpression increased the half maximal inhibitory rate (IC50) of cisplatin, promoted colony formation and tumor xenografts growth, and reduced cell apoptosis of ovarian cancer cells under cisplatin treatment, while silencing circPBX3 showed opposite effects. Furthermore, circPBX3 could interact with the RNA-binding protein IGF2BP2, thus increased the stability of ATP7A mRNA and elevated ATP7A protein level. In addition, silencing ATP7A in ovarian cancer cells abrogated the effect of circPBX3 overexpression on cisplatin tolerance. Our findings provided a novel role of circPBX3 in cisplatin resistance of ovarian cancer.

Thermodynamics Analysis of Multiple Microelements' Coupling Behavior in High Fatigue Resistance 50CrVA Spring Steel with Nanoparticles.

Solid solution and coupling precipitation behavior of multiple microelements in 50CrVA spring steel under different temperatures were analyzed based on thermodynamics. Quantitative relationships between the multiple microelements' contents and secondary phases, and their effects on fatigue life, were systematically studied in conjunction with the secondary phase microstructure characterization using scanning and transmission electron microscopy, etc. The solid solution contents of different microelements decreased as the temperature decreased, especially N and Ti, but the number of compounds gradually increased when the temperature decreased. Carbonitride constitutional liquation occurred in 50CrVA-S1# spring steel-containing microparticles, and without carbonitrides, constitutional liquation occurred in 50CrVA-S2# spring steel-containing nanoparticles. The experimental results indicate that the fatigue life reduces by about an order of magnitude when the secondary phase size changes from nanometers to microns, and the corresponding relationship among multiple microelements, microstructure of secondary phases, and fatigue life, was established in this spring steel.

Design of self-healable supramolecular hybrid network based on carboxylated styrene butadiene rubber and nano-chitosan.

In this paper, carboxylated styrene butadiene rubber (XSBR)/nano-chitosan (NCS) composites were prepared via a salt-forming reaction, in which NCS participated in constructing a supramolecular hybrid network. NCS served as multiple-functional cross-linker as well as reinforcer for XSBR. This turned out that the mechanical properties of XSBR could be improved by NCS, and simultaneously, the self-healing property was retained to utmost extent. With 20 wt% NCS, the tensile strength of NCS/XSBR composite was increased to 1.3 MPa, more than 2-time that of the neat XSBR, meanwhile, the healing efficiency was as high as to 92% after healing at ambient temperature for 24 h.

Injectable and Self-Healing Chitosan Hydrogel Based on Imine Bonds: Design and Therapeutic Applications.

Biological tissues can automatically repair themselves after damage. Examples include skin, muscle, soft tissue, etc. Inspired by these living tissues, numerous self-healing hydrogels have been developed recently. Chitosan-based self-healing hydrogels constructed via dynamic imine bonds have been widely studied due to their simple preparation, good biocompatibility, and automatic reparability under physiological conditions. In this mini-review, we highlighted chitosan-based self-healing hydrogels based on dynamic imine chemistry, and provided an overview of the preparation of these hydrogels and their bioapplications in cell therapy, tumor therapy, and wound healing.

Therapeutic benefit of mesenchymal stem cells in pregnant rats with angiotensin receptor agonistic autoantibody-induced hypertension: Implications for immunomodulation and cytoprotection.

Immunomodulation by mesenchymal stem cells (MSCs) is potentially important for maintaining peripheral tolerance. Preeclampsia may be due to maternal immune rejection of the genetically foreign fetus. This study aimed to investigate the biological function of human umbilical cord-derived mesenchymal stem cells (HU-MSCs) for the treatment of angiotensin receptor agonistic autoantibody (AT1-AA)-induced hypertension during pregnancy. HU-MSCs were isolated, cultured, and labeled in vitro. AT1-AA and HU-MSCs were administered to pregnant rats. Green fluorescent protein (GFP)-positive HU-MSCs infused in vivo were identified by immunofluorescence. Systolic blood pressure (SBP) was evaluated. The effects of HU-MSCs on fetal weight, kidney burden, and spiral artery remodeling, as well as on the expression of tumor necrosis factor α (TNF-α), interleukin 10 (IL-10), and heme oxygenase 1 (HO-1), were investigated. The SBP levels in the HU-MSC-treated pregnant hypertension rats decreased by gestational day 19. The reduction in fetal weight was largely ameliorated after HU-MSC treatment. Lesion burden in the kidney was attenuated and spiral artery remodeling was improved in HU-MSC-treated pregnant hypertension rats. However, green fluorescent protein (GFP)-labeled cells were sparingly observed in the kidney and placenta. Intravenous infusion of HU-MSCs into AT1-AA-induced rats significantly downregulated serum TNF-α levels and upregulated IL-10 levels, concomitant with increased placenta and mesometrial triangle (MT) HO-1 expression. Taken together, intravenous infusion of HU-MSCs ameliorates AT1-AA-induced pregnancy hypertension, intrauterine growth retardation, kidney impairment, and spiral artery remodeling impairment. Moreover, the potential benefits of HU-MSCs may be attributable to both an interference with the pathogenic immune response and a paracrine cytoprotective action.

Double-stranded-RNA-specific adenosine deaminase 1 (ADAR1) is proposed to contribute to the adaptation of equine infectious anemia virus from horses to donkeys.

Equine infectious anemia virus (EIAV) is a member of the genus Lentivirus of the family Retroviridae. Horses are the most susceptible equids to EIAV infection and are therefore the primary hosts of this virus. In contrast, infected donkeys do not develop clinically active equine infectious anemia (EIA). This phenomenon is similar to what has been observed with HIV-1, which fails to induce AIDS in non-human primates. Interestingly, Shen et al. developed a donkey-tropic pathogenic virus strain (EIAVDV117, DV117) by serially passaging a horse-tropic pathogenic strain, EIAVLN40 (LN40), in donkeys. LN40, which was generated by passaging a field isolate in horses, displayed enhanced virulence in horses but caused no clinical symptoms in donkeys. Infection with DV117 induced acute EIA in nearly 100 % of donkeys. Genomic analysis of DV117 revealed a significantly higher frequency of A-to-G substitutions when compared to LN40. Furthermore, detailed analysis of dinucleotide editing showed that A-to-G mutations had a preference for 5'TpA and 5'ApA. These results strongly implicated the activity of the adenosine deaminase, ADAR1, in this type of mutation. Further investigation demonstrated that overexpression of donkey ADAR1 increased A-to-G mutations within the genome of EIAV. Together with our previous finding that multiple mutations in multiple genes are generated in DV117 during its adaptation from horses to donkeys, the present study suggests that ADAR1-induced A-to-G mutations occur during virus adaption to related new hosts contributing to the alteration of EIAV host tropism.

Beneficial effect of human umbilical cord-derived mesenchymal stem cells on an endotoxin-induced rat model of preeclampsia.

Mesenchymal stem cells (MSCs), which exhibit the property of immune-modulation, have been shown to treat various diseases, including pulmonary hypertension. There is a functional similarity between the pulmonary circulation and the placenta, but it remains to be elucidated whether MSCs can be applied to treat endotoxin-induced hypertension during pregnancy; therefore, the aim of the present study was to investigate the therapeutic effect of a human umbilical cord-derived MSC infusion on endotoxin-induced hypertension during pregnancy. Rats were randomly divided into three groups (n=7 per group): Control, endotoxin-treated and endotoxin + MSCs. The model of preeclampsia (PE) was established via the intravenous injection of endotoxin. In the endotoxin + MSCs group, MSCs at 2×106 cells/rat were injected via the vena caudalis. The blood pressure, urine protein and number of white blood cells were measured. In addition, the protein expression levels of the pro-inflammatory cytokines interleukin (IL)-1ß and tumor necrosis factor-α (TNF-α) and the anti-inflammatory cytokine IL-10 were examined by ELISA. The blood pressure, levels of urine protein and number of white blood cells in the endotoxin-treated group were significantly higher than those in the control group (P<0.05); however, this increase was significantly attenuated in the endotoxin + MSCs group (P<0.05). In addition, the application of MSCs significantly reduced the levels of pro-inflammatory TNF-α and IL-1ß and increased the levels of anti-inflammatory IL-10 in the endotoxin-treated rats. In conclusion, umbilical cord-derived MSCs have a protective effect in an endotoxin-induced model of PE, and this effect is likely elicited through the suppression of inflammatory factors. Umbilical cord-derived MSC-based therapy may provide a potential therapeutic method for endotoxin-induced hypertension during pregnancy.

Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) promotes EIAV replication and infectivity.

Adenosine deaminases that act on RNA (ADARs) have been reported to be functional on various viruses. ADAR1 may exhibit antiviral or proviral activity depending on the type of virus. Human immunodeficiency virus (HIV)-1 is the most well-studied lentivirus with respect to its interaction with ADAR1, and variable results have been reported. In this study, we demonstrated that equine ADAR1 (eADAR1) was a positive regulator of equine infectious anemia virus (EIAV), another lentivirus of the Retroviridae family. First, eADAR1 significantly promoted EIAV replication, and the enhancement of viral protein expression was associated with the long terminal repeat (LTR) and Rev response element (RRE) regions. Second, the RNA binding domain 1 of eADAR1 was essential only for enhancing LTR-mediated gene expression. Third, in contrast with APOBEC proteins, which have been shown to reduce lentiviral infectivity, eADAR1 increased the EIAV infectivity. This study indicated that eADAR1 was proviral rather than antiviral for EIAV.

[Clinical analysis of cervical screening in 2329 pregnant women].

OBJECTIVE: To study the cytopathologic characteristics of cervical diseases in pregnant women and the outcomes of the postpartum women to provide evidence for prevention and treatment of cervical cancer. METHODS: This study was conducted among 2329 pregnant women undergoing routine gestational examinations between September, 2012 and September, 2013. The women with abnormal cytological findings by Thin-prep cytology test (TCT) were followed up and colposcopy and cervical biopsy were performed. The TCT results of these women were compared with those of 32 491 non-pregnant women in Zhongshan Cervical Cancer Mass Screening Program. RESULTS: Of the 2329 pregnant women, a total of 97 patients had abnormal TCT results (4.16%). Cervical biopsy were performed for 14 patients (14.43%), and 8 (57.14%) of them had evidence of cervical intraepithelial neoplasia (CIN) or cancer on biopsy. In the 32491 non-pregnant women in the mass screening program, 1383 (4.26%) women had abnormal TCT results and cervical biopsy were performed for 248 patients (17.93%), among whom 148 (59.68%) had evidence of CIN or cancer on biopsy. The rate of high-grade squamous intraepithelial lesion (HSIL) was significantly higher in non-pregnant women than in pregnant women (P=0.033), but the total rate of cytological abnormalities were comparable between them (P=0.911). The patients with CIN had regular examinations during pregnancy and postpartum follow-up showed no invasive carcinoma. CONCLUSION: Pregnancy is not a risk factor to accelerate the progress of cervical lesions, and most of the cervical lesions are relieved or show no progression in the postpartum women, suggesting the feasibility of follow-up during pregnancy and postpartum reevaluation for patients with CIN in pregnancy.

Equine viperin restricts equine infectious anemia virus replication by inhibiting the production and/or release of viral Gag, Env, and receptor via distortion of the endoplasmic reticulum.

UNLABELLED: Viperin is an endoplasmic reticulum (ER)-associated multifunctional protein that regulates virus replication and possesses broad antiviral activity. In many cases, viperin interferes with the trafficking and budding of viral structural proteins by distorting the membrane transportation system. The lentivirus equine infectious anemia virus (EIAV) has been studied extensively. In this study, we examined the restrictive effect of equine viperin (eViperin) on EIAV replication and investigated the possible molecular basis of this restriction to obtain insights into the effect of this cellular factor on retroviruses. We demonstrated that EIAV infection of primary equine monocyte-derived macrophages (eMDMs) upregulated the expression of eViperin. The overexpression of eViperin significantly inhibited the replication of EIAV in eMDMs, and knockdown of eViperin transcription enhanced the replication of EIAV in eMDMs by approximately 45.8%. Further experiments indicated that eViperin restricts EIAV at multiple steps of viral replication. The overexpression of eViperin inhibited EIAV Gag release. Both the α-helix domain and radical S-adenosylmethionine (SAM) domain were required for this activity. However, the essential motifs in SAM were different from those reported for the inhibition of HIV-1 Gag by human viperin. Furthermore, eViperin disrupted the synthesis of both EIAV Env and receptor, which consequently inhibited viral production and entry, respectively, and this disruption was dependent on the eViperin α-helix domain. Using immunofluorescence assays and electron microscopy, we demonstrated that the α-helix domain is responsible for the distortion of the endoplasmic reticulum (ER). Finally, EIAV did not exhibit counteracting eViperin at the protein level. IMPORTANCE: In previous studies, viperin was indicated as restricting virus replications primarily by the inhibition of virus budding. Here, we show that viperin may have multiple antiviral mechanisms, including the reduction of EIAV Gag budding and Env expression, and these activities are dependent on different viperin domains. We especially demonstrate that the overexpression of viperin inhibits EIAV entry by decreasing the level of virus receptor. Therefore, viperin restriction of viruses is determined largely by the dependence of virus on the cellular membrane transportation system.

Cervical cancer screening and analysis of potential risk factors in 43,567 women in Zhongshan, China.

OBJECTIVE: The objective of this study was to establish a program model for use in wide-spread cervical cancer screening. METHODS: Cervical cancer screening was conducted in Zhongshan city in Guangdong province, China through a coordinated network of multiple institutes and hospitals. A total of 43,567 women, 35 to 59 years of age, were screened during regular gynecological examinations using the liquid-based ThinPrep cytology test (TCT). Patients who tested positive were recalled for further treatment. RESULTS: The TCT-positive rate was 3.17%, and 63.4% of these patients returned for follow-up. Pathology results were positive for 30.5% of the recalled women. Women who were younger than 50 years of age, urban dwelling, low-income, had a history of cervical disease, began having sex before 20 years of age, or had sex during menstruation, were at elevated risk for a positive TCT test. The recall rate was lower in women older than 50 years of age, urban dwelling, poorly educated, and who began having sex early. A higher recall rate was found in women 35 years of age and younger, urban dwelling, women who first had sex after 24 years of age, and women who had sex during menstruation. The positive pathology rate was higher in urban women 50 years of age and younger and women who tested positive for human papillomavirus. CONCLUSION: An effective model for large-scale cervical cancer screening was successfully established. These results suggest that improvements are needed in basic education regarding cervical cancer screening for young and poorly educated women. Improved outreach for follow-up is also necessary to effectively control cervical cancer.