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Background: Colorectal cancer (CRC) is a considerable global health issue. Dioscin, a compound found in several medicinal plants, has shown potential anticancer effects., Aim: To find the relationship between CRC cells (HCT116) and diosgenin and clarified their mechanisms of action., Methods: CRC cell line HCT116 was cultured by dividing cells into control and dioscin groups (dioscin + Jagged 1 group; Jagged 1 group, 5 μg/mL; and dioscin group, 2.5 μg/mL). The dioscin groups were given different concentrations of dioscin. Cell Counting Kit-8 was chosen for testing cell viability in different groups. Flow cytometry was established to undiscover the apoptosis rate of human liver cancer cell line 11. Real-time PCR as well as Western blot analyses were applied to reveal the expression levels of caspase-3, Notch, and other proteins. Transwell and scratch experiments were conducted to assess cell migration and invasion abilities., Results: This study indicated that dioscin restricted the growth of HCT116 cells, boosted cell apoptosis, and rose the Bax / Bcl-2 ratio as well as the expression of Caspase-3 . Dioscin also inhibited physiological activities, for instance cell migration, and significantly reduced the expression levels of proteins for instance Notch1 ( P < 0.05). Dioscin partially reversed the effects of Jagged 1., Conclusion: Dioscin exerts a certain inhibitory effect on HCT116, and its mechanism of action may be linked, with the inhibition of the Notch1 signaling pathway., Competing Interests: Conflict-of-interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Depression is a pervasive and often undetected mental health condition, which poses significant challenges for early diagnosis due to its silent and subtle nature. To evaluate exhaled volatile organic compounds (VOCs) as non-invasive biomarkers for the detection of depression using a virtual surface acoustic wave sensors array (VSAW-SA). A total of 245 participants were recruited from the Hangzhou Community Health Service Center, including 38 individuals diagnosed with depression and 207 control subjects. Breath samples were collected from all participants and subjected to analysis using VSAW-SA. Univariate and multivariate analyses were employed to assess the relationship between VOCs and depression. The findings revealed that the responses of virtual sensor ID 14, 44, 59, and 176, which corresponded respectively to ethanol, trichloroethylene or isoleucine, octanoic acid or lysine, and an unidentified compound, were sensitive to depression. Taking into account potential confounders, these sensor responses were utilized to calculate a depression detection indicator. It has a sensitivity of 81.6% and a specificity of 81.6%, with an area under the curve of 0.870 (95% CI = 0.816-0.923). Conclusions: exhaled VOCs as non-invasive biomarkers of depression could be detected by a VSAW-SA. Large-scale cohort studies should be conducted to confirm the potential ability of the VSAW-SA to diagnose depression., (Creative Commons Attribution license.)

Although many researchers of Parkinson's disease (PD) have shifted their focus from the central nervous system (CNS) to the peripheral blood, a significant knowledge gap remains between PD severity and the peripheral immune response. In the current study, we aimed to map the peripheral immunity atlas in peripheral blood mononuclear cells (PBMCs) from PD patients and healthy controls using single-cell RNA sequencing (scRNA-seq). Our study employed scRNA-seq analysis to map the peripheral immunity atlas in PD by profiling PBMCs from PD-Early, PD-Late patients and matched controls. By enlarging the blood sample size, we validated the roles of NK cells in numerous immune-related biological processes. We also detected the infiltration of NK cells into the cerebral motor cortex as the disease progressed, using human brain sections, and elucidated the communication between the periphery and CNS and its implications for PD. As a result, cell subpopulation atlases in PBMCs from PD patients and healthy controls along with differentially expressed genes in NK cells were identified by scRNA-seq analysis, representing 6 major immune cell subsets among which NK cells declined in the progression of PD. We further validated NK cell reduction in increasing samples and found that they participated in numerous immune-related biological processes and infiltration into the cerebral motor cortex as the disease proceeded, evidencingd the close communication between the peripheral immune response and CNS. Strikingly, XCL2 positively correlated with PD severity, with good predictive performance of PD and specific expression in subclusters C2 and C5 of NK cells. All these findings delineated the critical role of peripheral immune response mediated by NK cells in the pathogenesis of PD. NK cell-specific XCL2 could be used as a diagnostic marker for treating PD. The indispensable function of NK cells and NK cell-specific molecular biomarkers highlighted the implication of the peripheral immune response in PD progression. Trial registration: ChiCTR, ChiCTR1900023975. Registered 20 June 2019 - Retrospectively registered, https://www.chictr.org.cn/showproj.html?proj=31035 ., (© 2024. The Author(s).)

Background: Hexavalent chromium (Cr (VI)) is highly carcinogenic to humans. Ascorbic acid (AA) deficiency can be hazardous to health. And the dual-effect fluorescence detection of them is an important research topic. Carbon dots (CDs) based on cellulose are excellent candidates for the fluorescence probes due to their low cost and environmental friendliness. But most of them exhibit shortwave emission, small Stokes shift and poor fluorescence performance, all of which limit their use. Therefore, there is an urgent need for cellulose CDs with longer emission wavelengths and larger Stokes shifts in dual-effect fluorescence detection of Cr (VI) and AA., Results: Under optimal conditions (180 °C, 12 h), we prepared cellulose-based nitrogen-doped carbon dots (N-CDs) by a simple one-step hydrothermal process, which display longer emission wavelengths (ex: 370 nm, em: 510 nm), larger Stokes shifts (140 nm) and high fluorescence quantum yield (QY: 19.27 %). The continuous "turn-off" and "turn-off-on" fluorescence detection platforms were constructed based on the internal filtering effect (IFE) between Cr 6+ and N-CDs, and Cr 6+ reduced to Cr 3+ by AA at pH = 6. The platform has been successfully simultaneous detect Cr (VI) and AA with a wide range of 0.01-40 μM and 0.1-100 μM. And the lowest limits of detection (LOD) are 0.0303 μM and 0.072 μM, respectively. In the presence of some other metals, non-metal ions and water-soluble acids in the fruits, this fluorescent platform can demonstrate a high level of interference immunity., Significance and Novelty: This represents the first yellow-green cellulose-based N-CDs with large Stokes shift for dual-effect detection of Cr (VI) and AA in real water samples and fresh fruits. The fluorescence detection platform has the advantage of low volume detection. Less than 2 mL of sample is required for testing and results are available in <5 min. This method is rare and supply a novel idea for the quantitative monitoring of Cr (VI) and AA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Hemorrhagic varicella (HV) is a particular form of chicken pox.,with high mortality in adults. This form of the disease is rare, to date, approximately 4 cases have been reported. Occasional cases of HV have been documented in adults with hematologic disorders or other diseases. While there is one reported case of simultaneous reactivation of cytomegalovirus in an adult with chickenpox, there is a lack of information regarding changes in liver function indicators for such patients. This is unfortunate, as CMV reactivation can further exacerbate liver failure and increase mortality. In this report, we present a case of hemorrhagic varicella reactivation with cytomegalovirus and provide some relevant discussions., Case Presentation: We present the case of a 25-year-old male with HV, who had a history of nephrotic syndrome generally controlled with orally administered prednisone at a dosage of 50 mg per day for two months. The patient arrived at the emergency room with complaints of abdominal pain and the presence of hemorrhagic vesicles on his body for the past 3 days. Despite medical evaluation, a clear diagnosis was not immediately determined. Upon admission, the leukocyte count was recorded as 20.96 × 10 9 /L on the first day, leading to the initiation of broad-spectrum antibiotic treatment. Despite the general interpretation that a positive IgG and a negative IgM indicate a previous infection, the patient's extraordinarily elevated IgG levels, coupled with a markedly increased CMV DNA quantification, prompted us to suspect a reactivation of the CMV virus. In light of these findings, we opted for the intravenous administration of ganciclovir as part of the treatment strategy. Unfortunately,,the patient succumbed to rapidly worsening symptoms and passed away. Within one week of the patient's demise, chickenpox gradually developed in the medical staff who had been in contact with him. In such instances, we speculate that the patient's diagnosis should be classified as a rare case of hemorrhagic varicella., Conclusion: Swift identification and timely administration of suitable treatment for adult HV are imperative to enhance prognosis., (© 2024. The Author(s).)

Pulmonary hypertension (PH) is a severe clinical syndrome with pulmonary vascular remodeling and poor long-term prognosis. Neurotensin receptor 1 (Ntsr1), serve as one of the G protein-coupled receptors (GPCRs), implicates in various biological processes, but the potential effects of Ntsr1 in PH development are unclear. The Sugen/Hypoxia (SuHx) or monocrotaline (MCT) induced rat PH model was used in our study and the PH rats showed aggravated pulmonary artery remodeling and increased right ventricular systolic pressure (RVSP). Our results revealed that Ntsr1 induced endoplasmic reticulum (ER) stress response via ATF6 activation contributed to the development of PH. Moreover, RNA-sequencing (RNA-seq) and phosphoproteomics were performed and the Ntsr1-JAK2-STAT3-thrombospondin 1 (Thbs1)-ATF6 signaling was distinguished as the key pathway. In vitro, pulmonary artery smooth muscle cells (PASMCs) under hypoxia condition showed enhanced proliferation and migration properties, which could be inhibited by Ntsr1 knockdown, JAK2 inhibitor (Fedratinib) treatment, STAT3 inhibitior (Stattic) treatment, Thbs1 knockdown or ATF6 knockdown. In addition, adeno-associated virus 1 (AAV1) were used to knockdown the expression of Ntsr1, Thbs1 or ATF6 in rats and reversed the phenotype of PH. In summary, our results reveal that Ntsr1-JAK2-STAT3-Thbs1 pathway can induce enhanced ER stress via ATF6 activation and increased PASMC proliferation and migration capacities, which can be mechanism of the pulmonary artery remodeling and PH. Targeting Ntsr1 might be a novel therapeutic strategy to ameliorate PH., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest. All authors have carefully reviewed and complied with the journal's authorship agreement., (Copyright © 2024. Published by Elsevier Inc.)

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, and recent epidemiological studies suggested type 2 diabetes mellitus (T2DM) is an independent risk factor for the development of AF. Zinc finger and BTB (broad-complex, tram-track and bric-a-brac) domain containing 16 (Zbtb16) serve as transcriptional factors to regulate many biological processes. However, the potential effects of Zbtb16 in AF under T2DM condition remain unclear. Here, we reported that db/db mice displayed higher AF vulnerability and Zbtb16 was identified as the most significantly enriched gene by RNA sequencing (RNA-seq) analysis in atrium. In addition, thioredoxin interacting protein (Txnip) was distinguished as the key downstream gene of Zbtb16 by Cleavage Under Targets and Tagmentation (CUT&Tag) assay. Mechanistically, increased Txnip combined with thioredoxin 2 (Trx2) in mitochondrion induced excess reactive oxygen species (ROS) release, calcium/calmodulin-dependent protein kinase II (CaMKII) overactivation, and spontaneous Ca 2+ waves (SCWs) occurrence, which could be inhibited through atrial-specific knockdown (KD) of Zbtb16 or Txnip by adeno-associated virus 9 (AAV9) or Mito-TEMPO treatment. High glucose (HG)-treated HL-1 cells were used to mimic the setting of diabetic in vitro. Zbtb16-Txnip-Trx2 signaling-induced excess ROS release and CaMKII activation were also verified in HL-1 cells under HG condition. Furthermore, atrial-specific Zbtb16 or Txnip-KD reduced incidence and duration of AF in db/db mice. Altogether, we demonstrated that interrupting Zbtb16-Txnip-Trx2 signaling in atrium could decrease AF susceptibility via reducing ROS release and CaMKII activation in the setting of T2DM., (© 2024. The Author(s).)

Background: The relationship between fibrosis-4 (FIB-4) index and all-cause mortality in critically ill patients with alcohol use disorder (AUD) is unclear. The present study aimed to investigate the predictive ability of FIB-4 for all-cause mortality in critically ill AUD patients and the association between them., Methods: A total of 2528 AUD patients were included using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. FIB-4 was calculated for each patient using the existing formula. The patients were equally divided into four groups based on the quartiles of FIB-4. Multivariate logistic regression and Cox proportional hazard model were used to evaluate the association of FIB-4 with in-hospital mortality, 28-day mortality and 1-year mortality. Kaplan-Meier curves were used to analyse the incidence of 28-day mortality among four groups., Results: FIB-4 was positively associated with 28-day mortality of AUD patients with hazard ratio (HR) of 1.354 [95% confidence interval (CI) 1.192-1.538]. There were similar trends in the in-hospital mortality [odds ratio (OR): 1.440, 95% CI (1.239-1.674)] and 1-year mortality [HR: 1.325, 95% CI (1.178-1.490)]., Conclusion: Increased FIB-4 is associated with greater in-hospital mortality, 28-day mortality and 1-year mortality in critically ill AUD patients., (© 2023 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Stromal antigen 2 (STAG2), a subunit of the cohesin complex, is recurrently mutated in various tumors. However, the role of STAG2 in DNA repair and its therapeutic implications are largely unknown. Here it is reported that knockout of STAG2 results in increased double-stranded breaks (DSBs) and chromosomal aberrations by reducing homologous recombination (HR) repair, and confers hypersensitivity to inhibitors of ataxia telangiectasia mutated (ATMi), Poly ADP Ribose Polymerase (PARPi), or the combination of both. Of note, the impaired HR by STAG2-deficiency is mainly attributed to the restored expression of KMT5A, which in turn methylates H4K20 (H4K20me0) to H4K20me1 and thereby decreases the recruitment of BRCA1-BARD1 to chromatin. Importantly, STAG2 expression correlates with poor prognosis of cancer patients. STAG2 is identified as an important regulator of HR and a potential therapeutic strategy for STAG2-mutant tumors is elucidated., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Objective: To investigate the effect of vitamin D3 on mild cognitive impairment in type 2 diabetic mice and explore its possible mechanism., Methods: Male db/db mice were randomly divided into 4 groups: the diabetes mellitus (DM) group, the low dose [250 IU/(kg·d)], medium dose [500 IU/ (kg·d)] and high dose [1 000 IU/(kg·d)] vitamin D3 intervention groups. The db/m mice were enrolled as the normal control group. The mice in vitamin D3 groups were gavaged with corresponding concentration of vitamin D3 in corn oil, and the mice in the normal control group and the DM group were gavaged with corn oil. After being fed for 16 weeks, fasting blood glucose of mice in each group was measured at the end of 0, 4, 8 and 16 weeks, and the new object recognition experiment was conducted at the end of 16 weeks. At the end of the experiment, the hippocampi and cortices of mice in each group were collected, and the concentration of 5-hydroxytryptamine (5-HT) and interleukin-18 (IL-18) in the hippocampal tissues of mice in each group were determined by enzyme linked immunosorbent assay (ELISA). Immunohistochemical staining was used to observe the expression of nucleotide binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) in the hippocampal tissues of the mice., Results: Compared with the normal control group, the fasting blood glucose of mice in DM group was significantly increased ( P < 0.01). The exploration and discrimination index (DI) in the new object recognition experiment were significantly decreased ( P < 0.05). The concentrations of 5-HT in the hippocampal tissues of mice were significantly decreased ( P < 0.01). The concentrations of IL-18 in cortical tissues of mice were significantly increased ( P < 0.01) and the positive expression of NLRP3 in the hippocampal tissues was higher. However, compared with the DM group, the fasting blood glucose of mice was significantly decreased in the medium and high dose vitamin D3 groups at the end of 8 and 16 weeks ( P < 0.05 or P < 0.01). The exploration and DI of mice in the new object recognition experiment were significantly increased in high dose vitamin D3 group ( P < 0.05). The concentrations of 5-HT in hippocampal tissues were significantly increased ( P < 0.01) and the concentrations of IL-18 in cortical tissues were significantly decreased in the medium and high dose vitamin D3 groups ( P < 0.01). The positive expression of NLRP3 in hippocampal tissues was reduced in all the vitamin D3 groups., Conclusion: Vitamin D3 might reduce the inflammatory response by inhibiting the activity of NLRP3, and thus ameliorating mild cognitive impairment in type 2 diabetic mice.

As an important driving force, introgression plays an essential role in shaping the evolution of plant species. However, knowledge concerning how introgression affects plant evolution in agroecosystems with strong human influences is still limited. To generate such knowledge, we used InDel (insertion/deletion) molecular fingerprints to determine the level of introgression from japonica rice cultivars into the indica type of weedy rice. We also analyzed the impact of crop-to-weed introgression on the genetic differentiation and diversity of weedy rice, using InDel (insertion/deletion) and SSR (simple sequence repeat) molecular fingerprints. Results based on the STRUCTURE analysis indicated an evident admixture of some weedy rice samples with indica and japonica components, suggesting different levels of introgression from japonica rice cultivars to the indica type of weedy rice. The principal coordinate analyses indicated indica - japonica genetic differentiation among weedy rice samples, which was positively correlated with the introgression of japonica -specific alleles from the rice cultivars. In addition, increased crop-to-weed introgression formed a parabola pattern of dynamic genetic diversity in weedy rice. Our findings based on this case study provide evidence that human activities, such as the frequent change in crop varieties, can strongly influence weed evolution by altering genetic differentiation and genetic diversity through crop-weed introgression in agroecosystems.

High-temperature body-centered cubic (BCC) γ-U is effectively stablized by γ-(U,Zr) alloys that also make it feasible to use it as a nuclear fuel. However, relatively little research has focused on γ-(U,Zr) alloys due to their instability at room temperature. The effect of Zr composition on its mechanical properties is not clear yet. Herein, we perform molecular dynamics simulations to investigate the mechanical and dynamical stabilities of γ-(U,Zr) alloys under high temperatures, and we calculate the corresponding lattice constants, various elastic moduli, Vickers hardness, Debye temperature, and dynamical structure factor. The results showed that γ-U, β-Zr, and γ-(U,Zr) are all mechanically and dynamically stable at 1200 K, which is in good agreement with the previously reported high-temperature phase diagram of U-Zr alloys. We found that the alloying treatment on γ-U with Zr can effectively improve its mechanical strength and melting points, such as Vickers hardness and Debye temperature, making it more suitable for nuclear reactors. Furthermore, the Zr concentrations in γ-(U,Zr) alloys have an excellent effect on these properties. In addition, the dynamical structure factor reveals that γ-U shows different structural features after alloying with Zr. The present simulation data and insights could be significant for understanding the structures and properties of UZr alloy under high temperatures.

Members of the GAPDH family play important roles in plant growth and development, as well as in stress responses. Our aim was to identify stress resistance genes through systematic analysis of the GAPDH family in watermelon. This could not only provide genetic resources for stress resistance breeding, but also form a basis for the study of plant stress resistance mechanisms. Eight GAPDHs representing four types of plant GAPDH in watermelon were identified (ClGAPA/B, ClGAPC1-3, ClGAPCp1-2 and ClGAPN). A comprehensive analysis of physicochemical properties, chromosome distribution, evolutionary relationships, exon-intron structure and conserved motifs of watermelon GAPDHs was performed using bioinformatics. Expression characteristics were assessed by RT-qPCR. Based on RT-qPCR results, ClGAPC2 was screened as a candidate for subcellular localization analysis and functional verification in Arabidopsis thaliana. Eight GAPDHs were classified into four subfamilies. GAPDHs in each subgroup were generally conserved and shared similarities in structure and conserved motifs. ClGAPDHs had notable tissue specificity and different expression patterns in response to H 2 O 2 , chilling, salt, osmotic stress, heat, salicylic acid, gibberellin, brassinosterol, ethylene and abscisic acid treatments. Three ClGAPC genes, especially ClGAPC2, were markedly induced by several treatments. ClGAPC2 was located in the nucleus and cytoplasm of tabacum epidermal cells. The ClGAPC2 transgenic Arabidopsis showed enhanced tolerance to salinity at the germination stage. We suggest that ClGAPC2 plays important roles in the adaptation of watermelon to salinity. Our findings provided candidate genes for further improving the salt tolerance of watermelon., (© 2022 German Society for Plant Sciences, Royal Botanical Society of the Netherlands.)

The clinical application of cisplatin is limited by its adverse events, of which nephrotoxicity is the most commonly observed. In a cisplatin-induced pathological response, oxidative stress is one of the upstream reactions which inflicts different degrees of damages to the intracellular material components. Reactive oxygen species (ROS) are also one of the early signaling molecules that subsequently undergo a series of pathological reactions, such as apoptosis and necrosis. This review summarizes the mechanism of intracellular ROS generation induced by cisplatin, mainly from the consumption of endogenous antioxidants, destruction of antioxidant enzymes, induction of mitochondrial crosstalk between the endoplasmic reticulum by ROS and Ca 2+ , and destruction of the cytochrome P450 (CYP) system in the endoplasmic reticulum, all of which result in excessive accumulation of intracellular ROS and oxidative stress. In addition, studies demonstrated that natural antioxidants can protect against the cisplatin-induced nephrotoxicity, by reducing or even eliminating excess free radicals and also affecting other nonredox pathways. Therefore, this review on the one hand provides theoretical support for the research and clinical application of natural antioxidants and on the other hand provides a new entry point for the detailed mechanism of cisplatin nephrotoxicity, which may lay a solid foundation for the future clinical use of cisplatin., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Jie Zhou et al.)

Microscopy by Achromatic X-rays With Emission of Laminar Light (MAXWELL) is a new X-ray/visible technique with attractive characteristics including isotropic resolution in all directions, large-volume imaging and high throughput. An ultrathin, laminar X-ray beam produced by a Wolter type I mirror irradiates the sample stimulating the emission of visible light by scintillating nanoparticles, captured by an optical system. Three-dimensional (3D) images are obtained by scanning the specimen with respect to the laminar beam. We implemented and tested the technique with a high-brightness undulator at SPring-8, demonstrating its validity for a variety of specimens. This work was performed under the Synchrotrons for Neuroscience-an Asia-Pacific Strategic Enterprise (SYNAPSE) collaboration., (© 2022. The Author(s).)

In this study, we aimed to evaluate the effect of Nobiletin (NOB) on the placenta of Sprague-Dawley (SD) rats that had undergone reduced uterine perfusion pressure (RUPP) surgery and to evaluate the safety of NOB intervention during pregnancy. The results showed that NOB alleviated placental hypoxia, attenuated placental cell apoptosis, and inhibited placental damage in RUPP rats. No side effect of NOB intervention during pregnancy was observed. BeWo cell lines with P53 knockdown were then constructed using lentiviral transfection, and the P53 signaling pathway was found to be essential for NOB to reduce hypoxia-induced apoptosis of the BeWo cell lines. In summary, NOB attenuated hypoxia-induced placental damage by regulating the P53 signaling pathway, and those findings may contribute some insights into the role of NOB in placental development and the prevention of placental-related diseases.

Captopril can have nephrotoxic effects, which are largely attributed to accumulated renin and "escaped" angiotensin II (Ang II). Here we test whether angiotensin converting enzyme-1 (ACE1) inhibition damages kidneys via alteration of renal afferent arteriolar responses to Ang II and inflammatory signaling. C57Bl/6 mice were given vehicle or captopril (60 mg/kg per day) for four weeks. Hypertension was obtained by minipump supplying Ang II (400 ng/kg per min) during the second 2 weeks. We assessed kidney histology by periodic acid-Schiff (PAS) and Masson staining, glomerular filtration rate (GFR) by FITC-labeled inulin clearance, and responses to Ang II assessed in afferent arterioles in vitro. Moreover, arteriolar H 2 O 2 and catalase, plasma renin were assayed by commercial kits, and mRNAs of renin receptor, transforming growth factor-β (TGF-β) and cyclooxygenase-2 (COX-2) in the renal cortex, mRNAs of angiotensin receptor-1 (AT 1 R) and AT 2 R in the preglomerular arterioles were detected by RT-qPCR. The results showed that, compared to vehicle, mice given captopril showed lowered blood pressure, reduced GFR, increased plasma renin, renal interstitial fibrosis and tubular epithelial vacuolar degeneration, increased expression of mRNAs of renal TGF-β and COX-2, decreased production of H 2 O 2 and increased catalase activity in preglomerular arterioles and enhanced afferent arteriolar Ang II contractions. The latter were blunted by incubation with H 2 O 2 . The mRNAs of renal microvascular AT 1 R and AT 2 R remained unaffected by captopril. Ang II-infused mice showed increased blood pressure and reduced afferent arteriolar Ang II responses. Administration of captopril to the Ang II-infused mice normalized blood pressure, but not arteriolar Ang II responses. We conclude that inhibition of ACE1 enhances renal microvascular reactivity to Ang II and may enhance important inflammatory pathways.

Drug-metabolizing enzymes, particularly the cytochrome P450 (CYP450) monooxygenases, play a pivotal role in pharmacokinetics. CYP450 enzymes can be affected by various xenobiotic substrates, which will eventually be responsible for most metabolism-based herb-herb or herb-drug interactions, usually involving competition with another drug for the same enzyme binding site. Compounds from herbal or natural products are involved in many scenarios in the context of such interactions. These interactions are decisive both in drug discovery regarding the synergistic effects, and drug application regarding unwanted side effects. Herein, this review was conducted as a comprehensive compilation of the effects of herbal ingredients on CYP450 enzymes. Nearly 500 publications reporting botanicals' effects on CYP450s were collected and analyzed. The countries focusing on this topic were summarized, the identified herbal ingredients affecting enzyme activity of CYP450s, as well as methods identifying the inhibitory/inducing effects were reviewed. Inhibitory effects of botanicals on CYP450 enzymes may contribute to synergistic effects, such as herbal formulae/prescriptions, or lead to therapeutic failure, or even increase concentrations of conventional medicines causing serious adverse events. Conducting this review may help in metabolism-based drug combination discovery, and in the evaluation of the safety profile of natural products used therapeutically.

The valley degree of freedom of carriers in crystals is useful to process information and perform logic operations, and it is a key factor for valley application to realize valley polarization. Here, we propose a model that the valley polarization transition at different valley points (- K and K points) is produced by biaxial strain. Using first-principles calculations, we illustrate our idea with a concrete example of a Janus GdClF monolayer. The predicted GdClF monolayer is dynamically, mechanically and thermally stable, and is a ferromagnetic (FM) semiconductor with perpendicular magnetic anisotropy (PMA), valence band maximum (VBM) at valley points and a high Curie temperature ( T C ). Due to its intrinsic ferromagnetism and spin-orbit coupling (SOC), a spontaneous valley polarization will be induced, but the valley splitting is only -3.1 meV, which provides an opportunity to achieve valley polarization transition at different valley points by strain. In the considered strain range ( a / a 0 : 0.94-1.06), the strained GdClF monolayer always has an energy bandgap, strong FM coupling and PMA. The compressive strain is in favour of - K valley polarization, while the tensile strain is favorable for K valley polarization. The corresponding valley splittings at 0.96 and 1.04 strains are -44.5 meV and 29.4 meV, respectively, which are higher than the thermal energy at room temperature (25 meV). Due to its special Janus structure, both in-plane and out-of-plane piezoelectric polarizations can be observed. It is found that the direction of in-plane piezoelectric polarization can be overturned by strain, and the d 11 values at 0.96 and 1.04 strains are -1.37 pm V -1 and 2.05 pm V -1 , respectively. Our work paves the way to design ferrovalley materials for application in multifunctional valleytronic and piezoelectric devices by strain.

Background: The aim of this study was to investigate the efficacy of left atrial appendage closure (LAAC) for primary and secondary stroke prevention in patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF). Methods: This pilot study enrolled 36 patients with HCM and AF who underwent LAAC between April 2017 and December 2019, of whom 22 were for primary stroke prevention and 14 were for secondary prevention. Results: The patients enrolled in this study had non-obstructive (86.1%) or mild obstructive (13.9%) HCM. Patients in the Secondary Prevention Group had higher CHA2DS2-VASc scores (5.1 ± 1.4 vs. 2.6 ± 1.6, P < 0.001) and higher HAS-BLED scores (2.8 ± 1.0 vs. 1.5 ± 0.9, P < 0.001) compared with those in the Primary Prevention Group. Successful closure with satisfactory seals (residual leak ≤ 5 mm) was achieved in all patients, with complete occlusion in 86.4% of the Primary Prevention Group and 92.9% of the Secondary Prevention Group. Procedural-related complications included one pericardial effusion and one groin hematoma. One device-related thrombus was identified in the Secondary Prevention Group and resolved after anticoagulation. During a mean follow-up time of 28.4 months, one bleeding event was recorded. There were no thromboembolic events or deaths in either group, with 97.2% of the patients achieving freedom from anticoagulation therapy. Conclusions: Initial results suggest that LAAC can be a safe and feasible alternative for primary and secondary stroke prevention in selected patients with HCM and AF. Further studies with larger samples are required., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mo, Zhang, Yuan, Sun, Zhang, Li, Chen, Cai, Yu, Wang and Li.)

Tree ring data is of significance for reconstructing climate and predicting environmental dynamics. In order to accurately measure spacing and other parameters of Haloxylon ammodendron tree ring, we first assigned coordinate system to the scanned H. ammodendron disc PS images based on GIS, and then completed the H. ammodendron tree ring spacing measurement by using ENVI image classification software and GIS measuring tool. The measurement accuracy was proved by WinDENDRO tree ring analysis system. The results showed that there was no significant difference between those two methods ( P =0.63), and that the difference of paired mean value was 0.87 μm, indicating that the measured results were accurate and reliable. The constructed method in this study could be used to measure the spacing of H. ammodendron tree ring, which lay the foundation for the automatic measurement of tree ring parameters such as area and perimeter. Our method could replace the current professional tree ring analysis system for some ring parameter measurement. The study would contribute to the dendroclimatology analysis and the investigation on age structure of H. ammodendron population.

Guided bone regeneration technique is a conventional method to repair various bone defects among series of techniques for bone augmentation around implant. Due to the excellent mechanical properties and biological compatibility, titanium mesh has unique advantages in the application of guided bone regeneration technology, such as broad clinical indications, high stability in osteogenesis. Though there are still some complications during the application of titanium mesh, a number of studies have tried to prevent the complications, so as to increase the success rate of bone augmentation surgery. This review elaborates the characteristics of titanium mesh, conventional clinical applications, common complications in application, and the research progress of its application and improvement, in order to provide reference for the improvement of titanium mesh in clinical and research applications.

Objective: To investigate the influence of the protamine sulfate on endocytosis and intracellular stability of tetrahedral framework nucleic acid (tFNA)., Methods: Articular cartilage cells were collected from 3-day-old C57BL mice. Cells at passage 1-2 were used in the experiments. 4 single-strand DNAs (S1 was marked by Cy5) were utilized to synthesize tFNAs via annealing process and ultrafiltration for purification. High-performance capillary electrophoresis (HPCE) was used to verify synthesis of tFNAs and transmission electron microscope was used to photo morphological characteristics. The 1 mg/mL protamine sulfate solution was slowly dropped into newly synthesized tFNAs (N/P=5/1). Then, Zeta potential was detected. Cells were treated with 100 nmol/L tFNAs with protamine sulfate in Dulbecco's Modified Eagle's medium (DMEM) (Exp.1), 100 nmol/L tFNAs in DMEM (Exp.2), and DMEM (Control), respectively. Flow cytometry was used to quantitatively detect intracellular Cy5 fluorescence after 6 h and 12 h treatments. Immunofluorescence staining was used to qualitatively observe internalized Cy5 fluorescence after 12 h treatment by laser confocal microscope. Lysosome of living cells were stained with lysosome probe. Colocalization between lysosome and tFNAs was observed by laser confocal microscope., Results: After incubating protamine sulfate, negative potential was transformed into positive one ( (-1.567±0.163) mV to (4.700±0.484) mV). The fluorescence intensity of tFNAs in the Exp.1 group was higher than that of the Exp.2 group in 6 h and 12 h ( P <0.05). This was consistent with the results of immunofluorescence staining after 12 h. Colocalization of Cy5 fluorescence and lysosome in the Exp.1 group was more rare than that in the Exp.2 group at 6 h and 12 h. Furthermore, a large amount of Cy5 fluorescence was still seen in the Exp.1 group at 12 h, while Cy5 fluorescence of the Exp.2 group was less., Conclusion: Protamine sulfate can effectively enhance endocytosis, and to some extent it can achieve lysosome escape of tFNAs., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

Previous epidemiologic research has shown that phthalate exposure in pregnant women is related to birth outcomes in a sex-specific manner. These outcomes may be mediated by placental inflammation, which is the proposed biological mechanism. This is the first study to address the relationship between phthalate exposure and gene expression in placental inflammation in a sex-specific manner. We performed quantitative PCR to measure placental inflammatory mRNAs (CRP, TNF-α, IL-1β, IL-6, IL-10, MCP-1, IL-8, CD68, and CD206) in 2469 placentae that were sampled at birth. We estimated the associations between mRNA and urinary phthalate monoesters using multiple linear regression models. Mono-n-butyl phthalate (MBP) was correlated with higher IL-1β, IL-6, and CRP expression in placentae of male fetuses and with higher IL-6, CRP, MCP-1, IL-8, IL-10, and CD68 expression in placentae of female fetuses. Mono benzyl phthalate (MBzP) increased the expression of TNF-α, MCP-1, and CD68 only in placentae of male fetuses. Mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) was negatively correlated with CRP, MCP-1, and CD68 in placentae of female fetuses. Maternal phthalate exposure was associated with inflammatory variations in placental tissues. The associations were stronger in placentae of male than of female fetuses. Compared with the other metabolites, MBP plays a strong role in these associations. The placenta is worth being further investigated as a potential mediator of maternal exposure-induced disease risk in children.

Objectives: Post-stroke depression (PSD) is common consequence of stroke. However, today the majority of PSD patients remains untreated or inadequately treated, especially in the developing countries. Herein, we performed a meta-analysis to evaluate efficacy and safety of hyperbaric oxygen (HBOT) therapy for PSD., Patients and Methods: Seven electronic databases were comprehensively searched for randomized clinical trials (RCTs) from inception to May 2019. Outcome measures included response rate, depression severity, neurological deficit, physical disability and adverse events., Results: A total of 27 RCTs involving 2250 participants were identified. Patients in HBOT group had a higher response rate than patients in control group (response rate: 69.4% vs 51.2%, odds ratio [OR] = 2.51, 95% confidence interval [CI] [1.83-3.43], P = 0.000). HBOT significantly reduced Hamilton Depression (HAMD) -17 item scores (weighted mean difference [WMD]  = -4.33, 95% CI [-4.82 to -3.84], P = 0.000), HAMD-24 item scores (WMD = -4.31, 95% CI [-5.01 to -3.62], P = 0.000), National Institute of Health Stroke Scale (NIHSS) scores (WMD = -2.77, 95% CI [-3.57 to -1.98], P = 0.000), Chinese Stroke Scale (CSS) scores (WMD = -3.75, 95% CI [-5.12 to -2.38], P = 0.000) and Modified Scandinavian Stroke Scale (MASSS) scores (WMD = -3.66, 95% CI [-6.26 to -1.06], P = 0.000). HBOT also improved Barthel Index (WMD = 10.68, 95% CI [7.98-13.37], P = 0.000). In subgroup analysis, Group A of studies with hemorrhage patients accounting for less than 20% achieved more reduction of HAMD 17-item score (WMD = -4.47, 95% CI [-5.17 to -3.77], P = 0.000) than Group B of studies with hemorrhage patients no less than 20% (WMD = -3.73, 95% CI [-4.20 to -3.26], P = 0.000). In addition, patents with HBOT along with antidepressants treatment achieve superior results than patients with antidepressants monotherapy. Patients with HBOT monotherapy achieve a slightly higher response rate than patients with antidepressants monotherapy (OR = 1.29, 95% CI [1.04-1.60], P = 0.000). Besides, HBOT group reported less adverse events (9.6%vs16.6%, P < 0.05). The most frequent side-effect of HBOT is ear pain (26 cases)., Conclusion: Based on our pooled analysis, HBOT is effective and safe therapeutic approach for PSD. However, results should be cautiously interpreted due to a relatively poor methodological quality., (Copyright © 2020. Published by Elsevier B.V.)

MicroRNAs (miRNAs) are small non-coding RNAs (typically consisting of 18-25 nucleotides) that negatively control expression of target genes at the post-transcriptional level. Owing to the biological significance of miRNAs, miRTarBase was developed to provide comprehensive information on experimentally validated miRNA-target interactions (MTIs). To date, the database has accumulated >13,404 validated MTIs from 11,021 articles from manual curations. In this update, a text-mining system was incorporated to enhance the recognition of MTI-related articles by adopting a scoring system. In addition, a variety of biological databases were integrated to provide information on the regulatory network of miRNAs and its expression in blood. Not only targets of miRNAs but also regulators of miRNAs are provided to users for investigating the up- and downstream regulations of miRNAs. Moreover, the number of MTIs with high-throughput experimental evidence increased remarkably (validated by CLIP-seq technology). In conclusion, these improvements promote the miRTarBase as one of the most comprehensively annotated and experimentally validated miRNA-target interaction databases. The updated version of miRTarBase is now available at http://miRTarBase.cuhk.edu.cn/., (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Sources of background and background variation in a BEGe type HPGe detector located in a surface laboratory were identified. Different strategies for background reduction were applied. A cosmic veto was installed, and optimised using a digital acquisition system in list-mode with time-stamped data. This resulted in the reduction of total background by a factor of 1.4. Thermal and fast neutron fluxes were also calculated. The radon induced background component and its variation were significantly reduced., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Effective therapeutic targets against post-myocardial infarction (MI) arrhythmias remain to be discovered. We aimed to investigate the role of macrophages in post-MI arrhythmias. Methods : Mononuclear cell accumulation, macrophage polarization from M0 to M1 subset, and gap junction formation were analyzed in MI patients and MI mice by flow cytometry, immunofluorescence and patch clamping. Differentially expressed genes were identified by RNA sequencing. Macrophages and cardiomyocytes were cocultured in vitro, and the effects of gap junction and KCa3.1 on electrophysiological properties were assessed by patch clamping. The effects of KCa3.1 inhibition on post-MI arrhythmias were assessed by intracardiac stimulation and ambulatory electrocardiograms in vivo. Results : Percentage of pro-inflammatory mononuclear cells were significantly elevated in patients with post-MI arrhythmias compared with MI patients without arrhythmias and healthy controls (p<0.001). Macrophages formed gap junction with cardiomyocytes in MI border zones of MI patient and mice, and pro-inflammatory macrophages were significantly increased 3 days post-MI (p<0.001). RNA sequencing identified Kcnn4 as the most differentially expressed gene encoding ion channel, and the upregulation is mainly attributed to macrophage accumulation and polarization into pro-inflammatory subset. In vitro coculture experiments demonstrated that connection with M0 macrophages via gap junction slightly shortened the action potential durations (APDs) of cardiomyocytes. However, the APD90 of cardiomyocytes connected with M1 macrophages were significantly prolonged (p<0.001), which were effectively attenuated by gap junction inhibition (p=0.002), KCa3.1 inhibition (p=0.008), KCa3.1 silencing (p<0.001) and store-operated Ca 2+ channel inhibition (p=0.005). In vivo results demonstrated that KCa3.1 inhibition significantly decreased the QTc durations (p=0.031), intracardiac stimulation-induced ventricular arrhythmia durations (p=0.050) and incidence of premature ventricular contractions (p=0.030) in MI mice. Conclusion : Macrophage polarization leads to APD heterogeneity and post-MI arrhythmias via gap junction and KCa3.1 activation. The results provide evidences of a novel mechanism of post-MI heterogeneous repolarization and arrhythmias, rendering macrophages and KCa3.1 to be potential therapeutic targets., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: The urine concentrations of phthalate metabolites were used to estimate the cumulative risk assessment in preschool children in Ma'anshan of Anhui province. Methods: Based on the China-Anhui Birth Cohort, the demographic information and urine samples of 3 743 children were collected in Ma'anshan from April 2014 to April 2015. The concentrations of 7 metabolites' [monomethyl phthalate (MMP), monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl- 5-oxohexyl) phthalate (MEOHP) and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP)] of 5 phthalates [dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), butyl benzyl phthalate (BBzP), and di (2-ethylhexyl) phthalate (DEHP)] in the urine samples of the children were measured by solid-phase extration-triple quadrupole high performance liquid chromatography-tandem mass spectrometry-isotope method. In addition, the estimated daily intakes (EDIs) of 5 phthalates were calculated according to the metabolites' concentrations. Cumulative risk assessment was performed using hazard quotient (HQ) and hazard index (HI) methods. Results: The M ( Q(R) ) of seven metabolite concentrations were 29.58 (18.69-48.26), 26.65 (13.44-56.09), 256.86 (150.99-438.51), 0.12 (0.04-0.32), 6.27 (3.71-11.13), 17.94 (11.94-28.42) and 24.80 (16.05-40.32) μg/g creatinine, respectively. For the EDIs of 5 phthalates, DBP ranked first, followed by DEHP, DMP, DEP and BBzP with the M ( Q(R) ) of 7.54 (4.41-12.85), 3.35 (2.20-5.42), 0.75 (0.47-1.24), 0.71 (0.36-1.52) and 0.003 (0.001-0.009) μg/(kg·d), respectively. The HQ and HI varied with age, gender and sampling season, the differences were significant ( P <0.05). Conclusions: These results indicated that risk of cumulative exposure to phthalates was high in preschool children aged 3-6 years in Ma'anshan. Age, gender and sampling season were influencing factors.

Abnormal sub-pathways competitively regulated by long non-coding RNAs (lncRNAs) for postmenopausal osteoporosis (PO) based on integration of lncRNA-mRNA expression data and pathway network topologies were investigated. Interesting lncRNA-mRNA pairs were selected by Pearsons correlation coefficient (PCC) algorithm on the basis of lncRNA-miRNA and miRNA-mRNA interactions and gene expression profiles. Then, lncRNAs in interesting pairs were embedded into pathway graphs as signature nodes by linking to their regulated-mRNAs, and lncRNA competitively regulated pathways (LCRPs) were gained for PO patients. Moreover, sub-pathways were detected dependent on the shortest distance similarity and the pathway topology. The abnormal sub-pathways were determined utilizing the Wallenius approximation methods through evaluating the statistical significance of sub-pathways. In total 75 interesting lncRNA-mRNA pairs (representing 17 lncRNAs and 74 mRNAs) were identified. Subsequently, 42 LCRPs were extracted from pathway graphs by signature lncRNA regulated mRNAs. Moreover, 14 abnormal sub-pathways with P<0.05 were obtained between PO patients and controls, such as sub-pathways of PI3K-Akt signaling pathway and long-term potentiation. This finding may facilitate understanding the molecular mechanism of PO, and point a new direction to identify potential biomarkers for treatment and prevention of the disease.

Background: Ovarian cancer (OC) is associated with high mortality in gynecological oncology; this is mainly due to the low diagnosis rate. Exosomal miRNA has demonstrated potential as a tumor biomarker. We aimed to explore the diagnostic potential of serum exosomal miR-1307 and miR-375 for OC., Methods: The first six candidate miRNAs were selected from the previous literature. The relative quantification of qRT-PCR was used to screen for the stability of exosomal miRNAs, followed by validation of the cohort. ROC analysis was employed to analyze the specificity and sensitivity of exosomal miRNA., Results: MiR-1307 and miR-375 were confirmed stably existing in serum exosomes of OC. Moreover, miR-1307 and miR-375 were both significantly up-regulated in serum exosomes of OC compared to ovarian benign and healthy groups. The overexpressed miRNAs showed independent diagnostic power and enhanced the diagnostic accuracy of traditional biomarkers when combined with CA-125 and HE4. MiR-1307 was associated with tumor staging, and miR-375 was associated with lymph node metastasis of OC., Conclusion: Our results suggest that serum exosomal miR-1307 and miR-375 could serve as potential tumor biomarkers to improve diagnostic efficiency for OC.

Panax ginseng C.A. Meyer (ginseng) is an edible and traditional medicinal herb, which is reported to have a wide range of biological activity and pharmaceutical properties. There were more studies on ginsenoside and polysaccharides, but fewer on ginseng oligopeptides (GOPs), which are small molecule oligopeptides extracted from ginseng. The present study was designed to investigate the effects and underlying mechanism of ginseng oligopeptide (GOPs) on binge drinking-induced alcohol damage in rats. Sprague Dawley rats were randomly assigned to six groups ( n = 10), rats in normal control group and alcohol model group was administered distilled water; rats in four GOPs intervention groups (at a dose of 0.0625, 0.125, 0.25, 0.5 g/kg of body weight, respectively) were administered GOPs once a day for 30 days. Experiment rats were intragastrically administered ethanol at a one-time dose of 7 g/kg of body weight after 30 days. The liver injury was measured through traditional liver enzymes, inflammatory cytokines, expression of oxidative stress markers, and histopathological examination. We found that the GOPs treatment could significantly improve serum alanine aminotransferase and aspartate aminotransferase, plasma lipopolysaccharide, and inflammatory cytokine levels, as well as the oxidative stress markers that were altered by alcohol. Moreover, GOPs treatment inhibited the protein expression of toll-like receptor 4, and repressed the inhibitor kappa Bα and nuclear factor-κB p65 in the liver. These findings suggested that GOPs have a significant protective effect on binge drinking-induced liver injury, and the mechanism possibly mediated by the partial inhibition of lipopolysaccharide-toll-like receptor 4-nuclear factor-κB p65 signaling in the liver.

A prospective cohort study of a Chinese population was conducted to investigate the relationship between prenatal phthalates exposure and maternal hemoglobin or anemia. Based on the Ma'anshan Birth Cohort study, 7 phthalate metabolites were quantified in spot pregnancy urine samples (n = 9263) from 3269 pregnant women during each trimester. The maternal hemoglobin concentrations were obtained from electronic medical records at the same three time points for each participant during pregnancy. Anemia was defined as a hemoglobin concentration below 110 g/L in pregnant women. Repeated measures and trimester-specific analyses were used to estimate the effects of phthalates exposure on maternal hemoglobin and anemia. The prevalence of anemia was 3.6%, 27.0%, and 26.5% during the first, second and third trimester, respectively. Repeated measures analysis showed that hemoglobin concentrations decreased by 0.55, 0.19, 0.57, 0.49, and 0.54 g/L with each 1 ln-transformed concentration increase of MBP, MBzP, MEHP, MEOHP, and MEHHP, respectively. Exposure to MMP, MBP, MEHP, MEOHP, and MEHHP increased the risk of anemia by 1.11-fold, 1.21-fold, 1.20-fold, 1.13-fold, and 1.16-fold, respectively. Trimester-specific regression models stratified by the sample collection time during pregnancy generated consistent results. This is the first study focusing on the effect of prenatal phthalate exposures on hemoglobin or anemia in pregnant Chinese women. We found that prenatal phthalates exposure not only decreased the concentrations of hemoglobin but also showed associations with the prevalence of anemia. Associations appeared stronger for the subsample representing women pregnant with a male fetus than those pregnant with a female fetus. Anemia remains a moderate public health problem in China, and effective measures should be implemented., (Copyright © 2018. Published by Elsevier Ltd.)

Aim: To study the influence of frontalis muscle flap suspension on ocular surface by analyzing the clinical features and inflammatory cytokines., Methods: A prospective, observational case series. Thirty-one eyes of 25 patients with severe congenital blepharoptosis who underwent frontalis muscle flap suspension surgery with at least 6mo of follow-up were included in the study. The main outcome measures were margin reflex distance 1 (MRD 1 ), degree of lagophthalmos, ocular surface disease index (OSDI), fluorescein staining (Fl), tear break-up time (BUT), Schirmer I test, and inflammatory cytokine assay., Results: The degrees of lagophthalmos significantly increased after surgery. The OSDI scores significantly increased 1wk postoperatively and then decreased 4wk after operation. The Fl scores reflected corneal epithelial defects in sixteen patients at early stage postoperatively. The BUT and Schirmer I test values remained stable and did not show change compared to those before surgery. The inflammatory cytokines in conjunctival epithelial cells (including IL-1β, IL-6, IL-8, TNF-α, and IL-17A) significantly increased 1wk after the surgery ( P <0.001), then returned to the normal level at 24wk postoperatively. The levels of inflammatory cytokine IL-1β, IL-6, IL-8, TNF-α, and IL-17A elevated significantly and were positively correlated with OSDI and Fl scores., Conclusion: Frontalis muscle flap suspension surgery results in lagophthalmos in early period of post-operation and relieved after months. The elevation of inflammatory cytokines level may participate in the occurrence of corneal epithelial defects at the early postoperative stage.

Dental pulp stem cells (DPSCs) derived from the human dental pulp tissue have multiple differentiation capabilities, such as osteo/odontogenic differentiation. Therefore, DPSCs are deemed as ideal stem cell sources for tissue regeneration. As new nanomaterials based on DNA, tetrahedral DNA nanostructures (TDNs) have tremendous potential for biomedical applications. Here, the authors aimed to explore the part played by TDNs in proliferation and osteo/odontogenic differentiation of DPSCs, and attempted to investigate if these cellular responses could be driven by activating the canonical Notch signaling pathway. Upon exposure to TDNs, proliferation and osteo/odontogenic differentiation of DPSCs were dramatically enhanced, accompanied by up regulation of Notch signaling. In general, our study suggested that TDNs can significantly promote proliferation and osteo/odontogenic differentiation of DPSCs, and this remarkable discovery can be applied in tissue engineering and regenerative medicine to develop a significant and novel method for bone and dental tissue regeneration., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Asthma is a heterogeneous clinical syndrome characterized by airway inflammation, hyper-responsiveness and remodeling. Airway remodeling is irreversible by current antiasthmatic drugs, and it is the main cause of severe asthma. Airway smooth muscle cells (ASMCs) act as the main effector cells for airway remodeling; the proliferation and hypertrophy of which are involved in airway remodeling. Caveolin (Cav)- 1 is present on the surface of ASMCs, which is involved in cell cycle and signal transduction regulation, allowing ASMCs to change from proliferation to apoptosis. The extracellular signal-regulated kinase (ERK)1/2 signaling pathway is a common pathway regulated by various proliferative factors, which demonstrates a regulatory role in airway remodeling of asthma. There have been many studies on the correlation between vasoactive intestinal peptide (VIP) and airway reactivity and inflammation in asthma, but the functions and related mechanisms of ASMCs remain unclear. In this study, we established an airway remodeling model in asthmatic mice, and concluded that VIP inhibits airway remodeling in vivo. The in vitro effect of VIP on interleukin-13-induced proliferation of ASMCs was studied by examining the effects of VIP on expression of ERK1/2, phospho-ERK1/2 and Cav-1 in ASMCs, as well as changes in cell cycle distribution. VIP inhibited phosphorylation of the ERK1/2 signaling pathway and expression of Cav-1 on ASMCs and decreased the proportion of S phase cells in the cell cycle, thus inhibiting the proliferation of ASMCs. This study provides a novel therapeutic mechanism for the treatment of asthma., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To investigate the association between the internal exposure levels of phthalic acid esters (PAEs) and executive function (EF) of preschool children. Methods: Between October 2008 and October 2010, pregnant women who accepted pregnancy health care services in four municipal medical and health institutions in Ma'anshan city, Anhui Province, were recruited as study objects. A total of 5 084 pregnant women and 4 669 singleton live births were enrolled in this cohort. The follow-up study was conducted from April 2014 to April 2015. A total of 3 725 data-completed preschool children aged 3 to 6 years older entered in this study. The method of analysis seven metabolites of phthalates in urine was high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and divided objects into low ( P (0)- P (24)), medium ( P (25)- P (74)) and high ( P (75)- P (100)) groups according to their exposure concentrations. To investigate the executive function of preschool children, we used the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P). Univariate and multivariate statistical method was used to analyze the etiology association between the phthalate metabolites levels and preschool children's executive function. Results: In this study, 53.6% (1 997/3 725) of preschoolers were boys, children's age was (51.5±5.6) months. The detection rates of seven phthalate esters were: mono-n-methyl phthalate (MMP) was 99.89% (3 721/3 725); mono-ethyl phthalate (MEP) was 99.97% (3 724/3 725); mono-benzyl phthalate (MBzP) was 69.10% (2 574/3 725); mono-butyl phthalate (MBP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono- (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were 100.00% and mono-ethylhexyl phthalate (MEHP) was 99.95% (3 723/3 725). The median concentrations of the seven phthalate metabolites were: 17.71, 15.36, 0.07, 155.24, 10.73, 14.67, 3.59 µg/L, respectively. The median concentrations corrected by urinary creatinine were 29.65, 26.65, 0.12, 257.73, 17.94, 24.80, 6.27 µg/g Cr, respectively. The P (25) and P (7)5 concentration of the total PAEs metabolites corrected by urinary creatinine were 1.20 µmol/g Cr and 3.04 µmol/g Cr. After adjusted the relevant demographic information: children sex, children age in month, maternal age, parental education levels, household exposure to secondhand smoke and whether the child is the only child as confounds, multivariate logistic regression model showed that the risk of inhibitory self-control index (ISCI) dysplasia in MEHHP high concentration group and MEOHP high concentration group were 1.71 and 1.54 times ( OR= 1.71, 95 % CI: 1.11-2.62; OR= 1.54, 95 % CI: 1.01-2.34) than in low concentration group. The risk of ISCI dysplasia in total PAEs metabolites high concentration group was 1.55 times ( OR= 1.55, 95 % CI: 1.00-2.38) than in low concentration group. Conclusion: Phthalates exposure may damage the executive function of preschool children.

Objective: There is concern over the potential placental effects of prenatal phthalate exposure, and the potential adverse effects of prenatal phthalate exposure require further study; however, few data are available in humans. We investigated the associations between phthalate exposure in each trimester and both placental size and shape at birth., Methods: We measured the urinary concentrations of phthalate metabolites among 2725 pregnant women in the Ma'anshan Birth Cohort. Before collecting urine samples from each of the three trimesters, the pregnant women were interviewed via questionnaires. Placental information was obtained from hospital records. We estimated the sex-specific associations between urinary phthalate concentrations in each trimester and both placental size and shape at birth using adjusted multiple regression. A linear mixed model was used for the repeated measures analysis with subject-specific random intercepts and slopes for gestational age at sample collection to test the effect of phthalate levels on placental size and shape and to estimate the effect sizes., Results: Overall, placental breadth increased by 0.148cm (95% CI: 0.078, 0.218) with each 1 ln-concentration increase in MBP in the first trimester. The difference between placental length and breadth (length-breadth) decreased by 0.086cm (95% CI: -0.159, -0.012) and 0.149cm (95% CI: -0.221, -0.076) with each 1 ln-concentration increase in MMP and MBP, respectively, in the first trimester. In the second trimester, placental thickness increased by 0.017cm (95% CI: 0.006, 0.027), 0.020cm (95% CI: 0.004, 0.036), 0.028cm (95% CI: 0.007, 0.048), and 0.035cm (95% CI: 0.018, 0.053) with each 1 ln-concentration increase in MMP, MBP, MEOHP, and MEHHP, respectively. In the third trimester, placental thickness increased by 0.037cm (95% CI: 0.019, 0.056) and 0.019cm (95% CI: 0, 0.037) with each 1 ln-concentration increase in MBP and MEHP, respectively. Multiple linear regression for each offspring sex indicated that prenatal phthalate exposure increased placental thickness in both the first and second trimesters in males, whereas the corresponding relationship was close to null in females. Linear mixed models (LMMs) yielded similar results., Conclusion: Our results suggest the presence of associations between prenatal phthalate exposure and placental size and shape. Exposure to certain phthalates may cause the placenta to become thicker and more circular. Associations appeared stronger for the subsample representing male offspring than those for the subsample representing female offspring. Given the few studies on this topic, additional research is warranted., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Liposome is a promising carrier system for delivering bioactive molecules. However, the successful delivery of pH-sensitive molecules is still limited by the intrinsic instability of payloads in physiological environment. Herein, we developed a special liposome system that possesses an acidic micro-environment in the internal aqueous chamber to improve the chemical stability of pH-sensitive payloads. Curcumin-loaded liposomes (Cur-LPs) with varied internal pH values (pH 2.5, 5.0, or 7.4) were prepared. These Cur-LPs have similar particle size of 300 nm, comparable physical stabilities and analogous in vitro release profiles. Interestingly, the chemical stability of liposomal curcumin in 50% fetal bovine serum and its anticancer efficacy in vitro are both micro-environmental pH-dependent (Cur-LP-2.5 > Cur-LP-5.0 > Cur-LP-7.4). This serum stability still has space to be further enhanced to improve the applicability of Cur-LP. In conclusion, creating an acidic micro-environment in the internal chamber of liposome is feasible and efficient to improve the chemical stability of pH-sensitive payloads.

In this study, the effect factors and mechanisms of doxycycline hydrochloride (DOX) adsorption on copper nitrate modified biochar (Cu-BC) was investigated. Cu-BC absorbent was synthesized through calcination of peanut shells biomass at 450°C and then impregnation with copper nitrate. The Cu-BC has exhibited excellent sorption efficiency about 93.22% of doxycycline hydrochloride from aqueous solution, which was double higher than that of the unmodified biochar. The experimental results suggest that the adsorption efficiency of DOX on the Cu-BC is dominated by the strong complexation, electrostatic interactions between DOX molecules and the Cu-BC samples. Comprehensively considering the cost, efficiency and the application to realistic water, the Cu-BC hold the significant potential for enhancing the effectiveness to remove DOX from water., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A novel magnetic nanomaterial was synthesized by grafting nitrilotriacetic acid to magnetic graphene oxide (NDMGO), which was applied as an adsorbent for removing tetracycline (TC) from aqueous solutions. The nanomaterial was characterized using TG-DTA, SEM, TEM, XRD, VSM, XPS, Raman, BET surface area and zeta potential measurements. Several experimental conditions (solution pH, adsorption time, temperature, ionic strength and foreign ions) affecting the adsorption process were investigated. The results showed that the TC adsorption capacity could be affected by solution pH. The adsorption capacity of TC increased rapidly in the initial 20min and finally reached equilibrium was about 600min. The pseudo-second-order kinetics provided the better correlation for the experiment data. Various thermodynamic parameters indicated that the adsorption was a spontaneous and endothermic process. The presence of NaCl and background electrolytes in the solution had a slight influence on TC adsorption. Hydrogen bonds, amidation reaction, π-π and cation-π interaction between NDMGO and TC could be used to explain the adsorption mechanism. The regeneration experiment demonstrated that this nanomaterial possessed an excellent regeneration performance. Based on the experimental results and comparative analysis with other adsorbents, the NDMGO was a high-efficiency and reusable adsorbent for TC pollution control., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In this study, a methylation-sensitive amplification polymorphism analysis system was used to analyze DNA methylation level in three cotton accessions. Two disease-sensitive near-isogenic lines, PD94042 and IL41, and one disease-resistant Gossypium mustelinum accession were exposed to Verticillium wilt, to investigate molecular disease resistance mechanisms in cotton. We observed multiple different DNA methylation types across the three accessions following Verticillium wilt exposure. These included hypomethylation, hypermethylation, and other patterns. In general, the global DNA methylation level was significantly increased in the disease-resistant accession G. mustelinum following disease exposure. In contrast, there was no significant difference in the disease-sensitive accession PD94042, and a significant decrease was observed in IL41. Our results suggest that disease-resistant cotton might employ a mechanism to increase methylation level in response to disease stress. The differing methylation patterns, together with the increase in global DNA methylation level, might play important roles in tolerance to Verticillium wilt in cotton. Through cloning and analysis of differently methylated DNA sequences, we were also able to identify several genes that may contribute to disease resistance in cotton. Our results revealed the effect of DNA methylation on cotton disease resistance, and also identified genes that played important roles, which may shed light on the future cotton disease-resistant molecular breeding.

Objective: Curcumin has properties of anti-inflammation, anti-oxidation, anti-infection and anti-tumor, benefiting for the treatment of many diseases. The present study was aimed to investigate the role of curcumin in myocardial infarction (MI) and its potential mechanism involving transcription factor specific protein 1 (SP1)., Methods: After receiving curcumin, C57BL/6 mice subjected to left anterior descending (LAD) coronary artery occlusion to induce MI model. Infarct size was measured by triphenyl tetrazolium chloride staining. In vitro experiments, mouse cardiac myocytes (MCM) subjected to hypoxia after the incubation of curcumin, miR-7a/b and SP1 expression levels were detected by real-time PCR and western blot. Caspase-3 activity and TUNEL assay were performed to assess the cell apoptosis., Results: In animal experiments, curcumin significantly reduced the infarct size compared with the control. It also up-regulated miR-7a/b expression and down-regulated SP1 expression. In hypoxia-induced MCM, curcumin led to the decrease of cell apoptosis. Transfected MCM with miR-7a/b inhibitor, curcumin induced the decrease of cell apoptosis and SP1 expression was reversed. Transfected with pcDNA-SP1, the decrease of cardiac myocytes apoptosis after the treatment of curcumin was also reversed., Conclusion: Curcumin pre-treatment protected against hypoxia-induced cardiac myocytes apoptosis through the up-regulation of miR-7a/b and the down-regulation of SP1 expression., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Recently, much attention has been paid to DNA again due to the successful synthesis of DNA-based nanostructures that can enter cells via endocytosis and thus have great potential in biomedical fields. However, the impacts of DNA nanostructures on life activities of a living cell are unknown. Herein, the promotion effect of tetrahedral DNA nanostructure (TDN) on cell growth and the underlying molecular mechanisms are reported. Upon exposure to TDN, cell proliferation is significantly enhanced, accompanied by up-regulation of cyclin-dependent kinase like-1 gene, changes in cell cycle distribution, and up-regulation of the Wnt/β-catenin signaling-related proteins (β-catenin, Lef 1 and cyclin D). In contrast, single-stranded DNA (ssDNA) shows no such functions. Furthermore, TDN is able to reverse the inhibition effect of DKK1, a specific inhibitor for Wnt/β-catenin pathway. Hence, the Wnt/β-catenin pathway is the target for TDN to promote cell proliferation. The findings allow TDN to be a novel functional nanomaterial that has great potential in tissue repair and regeneration medicine.

Objectives: Recent studies have demonstrated the role of Cdr1as (or CiRS-7), one of the well-identified circular RNAs (circRNAs), as a miR-7a/b sponge or inhibitor in brain tissues or islet cells. This study aimed to investigate the presence of Cdr1as/miR-7a pathway in cardiomyocytes, and explore the mechanism underlying the function of miR-7a in protecting against myocardial infarction (MI)-induced apoptosis., Methods: Mouse MI injury model was established and evaluated by infarct size determination. Real-time PCR was performed to quantify the expression of Cdr1as and miR-7a in cardiomyocytes. Cell apoptosis was determined by caspase-3 activity analysis and flow cytometry assays with Annexin V/PI staining. Transfection of Cdr1as overexpressing plasmid and miR-7a mimic were conducted for gain-of-function studies. Luciferase reporter assay and western blot analysis were performed to verity potential miR-7a targets., Results: Cdr1as and miR-7a were both upregulated in MI mice with increased cardiac infarct size, or cardiomyocytes under hypoxia treatment. Cdr1as overexpression in MCM cells promoted cell apoptosis, but was then reversed by miR-7a overexpression. The SP1 was identified as a new miR-7a target, in line with previously identified PARP, while miR-7a-induced decrease of cell apoptosis under hypoxia treatment was proven to be inhibited by PARP-SP1 overexpression. Moreover, Cdr1as overexpression in vivo increased cardiac infarct size with upregulated expression of PARP and SP1, while miR-7a overexpression reversed these changes., Conclusions: Cdr1as also functioned as a powerful miR-7a sponge in myocardial cells, and showed regulation on the protective role of miR-7a in MI injury, involving the function of miR-7a targets, PARP and SP1.

Osteoarthritis is recognised to be an interactive pathological process involving the cartilage, subchondral bone and synovium. The signals from the synovium play an important role in cartilage metabolism, but little is known regarding the influence of the signalling from bone. Additionally, the collagenases and stromelysin-1 are involved in cartilage catabolism through mitogen-activated protein kinase (MAPK) signalling, but the role of the gelatinases has not been elucidated. Here, we studied the influence of osteoclastic signals on chondrocytes by characterising the expression of interleukin-1β (IL-1β)-induced gelatinases through MAPK signalling. We found that osteoclast-conditioned media attenuated the gelatinase activity in chondrocytes. However, IL-1β induced increased levels of gelatinase activity in the conditioned media group relative to the mono-cultured chondrocyte group. More specifically, IL-1β restored high levels of gelatinase activity in c-Jun N-terminal kinase inhibitor-pretreated chondrocytes in the conditioned media group and led to lower levels of gelatinase activity in extracellular signal-regulated kinase or p38 inhibitor-pretreated chondrocytes. Gene expression generally correlated with protein expression. Taken together, these results show for the first time that signals from osteoclasts can influence gelatinase activity in chondrocytes. Furthermore, these data show that IL-1β restores gelatinase activity through MAPK inhibitors; this information can help to increase the understanding of the gelatinase modulation in articular cartilage.

Hybrid coronary revascularization (HCR), a new minimally invasive procedure for patients requiring revascularization for multivessel coronary lesions, combines coronary artery bypass grafting (CABG) for left anterior descending (LAD) lesions and percutaneous coronary intervention (PCI) for non-LAD coronary lesions. However, available data related to outcomes comparing the 3 revascularization therapies is limited to small studies.We conducted a search in MEDLINE, EMBASE, and the Cochrane Library of Controlled Trials up to December 31, 2014, without language restriction. A total of 16 randomized trials (n=4858 patients) comparing HCR versus PCI or off-pump CABG (OPCAB) were included in this meta-analysis. The primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), all-cause death, myocardial infarction (MI), cerebrovascular events (CVE), and target vessel revascularization (TVR). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using random-effect and fixed-effect models. Ranking probabilities were used to calculate a summary numerical value: the surface under the cumulative ranking (SUCRA) curve.No significant differences were seen between the HCR and PCI in short term (in hospital and 30 days) with regard to MACCE (odds ratio [OR] = 0.51, 95% confidence interval [CI] 0.00-2.35), all-cause death (OR = 2.09, 95% CI 0.34-7.66), MI (OR = 1.02, 95% CI 0.19-2.95), CVE (OR = 4.45, 95% CI 0.39-19.16), and TVR (OR = 6.99, 95% CI 0.17-39.39). However, OPCAB had lower MACCE than HCR (OR = 0.19, 95% CI 0.00-0.95). In midterm (1 year and 3 year), in comparison with HCR, PCI had higher all-cause death (OR = 5.66, 95% CI 0.00-13.88) and CVE (OR = 4.40, 95% CI 0.01-5.68), and lower MI (OR = 0.51, 95% CI 0.00-2.86), TVR (OR = 0.53, 95% CI 0.05-2.26), and thus the MACCE (OR = 0.51, 95% CI 0.00-2.35). Off-pump CABG presented a better outcome than HCR with significant lower MACCE (OR = 0.17, 95% CI 0.01-0.68). Surface under the cumulative ranking probabilities showed that HCR may be the superior strategy for MVD and LMCA disease when regarded to MACCE (SUCRA = 0.84), MI (SUCRA = 0.76) in short term, and regarded to MACCE (SUCRA = 0.99), MI (SUCRA = 0.94), and CVE (SUCRA = 0.92) in midterm.Hybrid coronary revascularization seemed to be a feasible and acceptable option for treatment of LMCA disease and MVD. More powerful evidences are required to precisely evaluate risks and benefits of the 3 therapies for patients who have different clinical characteristics.

Cotton (Gossypium spp) is one of the most economically important crops that provide the world's most widely used natural fiber. Diseases such as Fusarium wilt and particularly Verticillium wilt seriously affect cotton production, and thus breeding for disease resistance is one of the most important goals of cotton breeding programs. Currently, potential exists to improve disease resistance in cultivated cotton. Increasing the understanding of the distribution, structure, and organization of genes or quantitative trait loci for disease resistance will help the breeders improve crop yield even in the event of disease. To facilitate the mapping of disease-resistance quantitative trait loci to achieve disease-resistant molecular breeding in cotton, it is necessary to develop polymorphic molecular markers. The objective of this study was to develop simple sequence repeat markers based on cotton expressed sequence tags for disease resistance. The efficacy of these simple sequence repeat markers, their polymorphisms, and cross-species transferability were evaluated. Their value was further investigated based on genetic diversity and evolution analysis. In this study, the unique sequences used to develop markers were compared with the G. arboretum and G. raimondii genome sequences to investigate their position, homology, and collinearity between G. arboretum and G. raimondii.

Objectives: Up to now, little research has been focussed on discovering how zeta potential independently affects polymeric nanoparticle (NP) cytotoxicity., Methods: Polymeric nanoparticles of gradient zeta potential ranging from -30 mv to +40 mv were fabricated using the same poly-3-hydroxybutyrate-co-3-hydroxyhexanoate (PHBHHx) biopolymer. Interaction forces between nanoparticles and cells were measured by atomic force microscopy (AFM). Cytotoxicity of the nanoparticles to cells was investigated by using MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay., Results: Four kinds of nanoparticle with similar sizes and gradient zeta potentials, were fabricated. Those with positive surface charges were found to be more toxic than those with negative surface charges. Positively charged nanoparticles or nanoparticles with higher 'like' charges, offered higher interaction force with cells., Conclusion: This work proposes a novel approach for investigating interaction between NPs and cells, and discloses the importance of controlling zeta potential in developing NPs-based formulations in the future., (© 2015 John Wiley & Sons Ltd.)