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Background and purpose: Hemorrhagic transformation (HT) is the most serious complication of intravenous thrombolysis in ischemic stroke patients. Inflammation plays a critical role in the pathological progression of HT. This study was to explore the relationship between fibrinogen-to-albumin ratio (FAR), a novel systemic inflammation biomarker, and HT after intravenous thrombolysis in patients with ischemic stroke. Methods: This retrospective study enrolled ischemic stroke patients who underwent intravenous thrombolysis between Jan 2017 to May 2022. The characteristic data of all patients at admission were retrospectively collected. The univariate and multivariate logistic regression analyses were performed to evaluate the correlation between FAR and HT after intravenous thrombolysis. The optimal cut-off value of FAR for predicting HT was determined by the receiver operating characteristic curve. Results: A total of 363 ischemic stroke patients were enrolled in the present study. Sixty-two patients had HT after intravenous thrombolysis. In multivariate regression analysis, FAR was significantly associated with HT (odds ratio [OR], 1.105; 95% confidential interval [CI], 1.029–1.186, P = 0.006). The receiver operating characteristic curve analysis indicated FAR predicts HT after intravenous thrombolysis with an AUC of 0.613 (95%CI, 0.530–0.695; P = 0.005) and an optimal cut-off value of 0.101. The correlation between FAR and HT after intravenous thrombolysis was still observed when patients were stratified according to FAR levels. A higher FAR level was independently related to the occurrence of HT after adjusting for the potential confounding factors. Conclusion: Higher FAR level was independently associated with HT after intravenous thrombolysis in patients with ischemic stroke. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke is a common cerebrovascular disease with high morbidity, disability, and mortality worldwide. Currently, recombinant tissue plasminogen activator is the main intravenous thrombolysis agent for the treatment of acute ischemic stroke within 4.5 h after onset. Hemorrhagic transformation (HT) is the most serious complication of intravenous thrombolysis, which can significantly aggravate clinical poor prognosis. Therefore, it is important to early predict the risk of post-thrombolysis HT in patients with acute ischemic stroke. Summary: Recently, several studies have reported that neuroimaging techniques have potential value in predicting HT after intravenous thrombolysis in patients with acute ischemic stroke. The corresponding neuroimaging parameters may be effective predictors of HT after intravenous thrombolysis. In this review, we summarized and discussed the application of neuroimaging techniques and related parameters in predicting HT after intravenous thrombolysis. Key Messages: Recognizing and understanding the predictive performance of neuroimaging parameters for HT may help assess the risk of HT after intravenous thrombolysis in patients with acute ischemic stroke and make an appropriate treatment decision. [ABSTRACT FROM AUTHOR]

Objective: To investigate the correlation between serum asymmetric dimethylarginine (ADMA) and the risk of ischaemic stroke and carotid atherosclerosis in adults. Methods: We systematically searched PubMed, EMBASE, Web of Science and other databases for relevant studies on serum ADMA and ischaemic stroke or carotid atherosclerosis, which were published from December 1980 to December 2019. The quality of the included studies was evaluated according to the Cochrane system evaluation standard. The difference in serum ADMA level between ischaemic stroke and control group was selected as the effect size (standardized mean difference, SMD). The pooled analysis was performed using Review Manager (V.5.3). Results: According to the selection criteria, thirteen studies were included in the meta‐analysis after screening. Nine studies compared ADMA levels between the ischaemic stroke group and healthy control group, involving a total of 1315 and 880 subjects in the two groups, respectively. Pooled effect sizes were calculated using the random‐effects model due to the high heterogeneity (I2 = 93%, P <.00001). The level of serum ADMA in patients with ischaemic stroke was significantly higher than that in healthy people (SDM = 0.69, 95% CI [0.32, 1.06], P =.0002). Seven of the thirteen articles compared ADMA levels between the carotid arteriosclerosis group and the healthy control group, with 559 and 330 subjects in the two groups, respectively. The random‐effects model was applied due to the high heterogeneity (I2 = 91%, P <.00001). The level of serum ADMA in patients with carotid arteriosclerosis was significantly higher than that in healthy people (SDM = 1.03, 95% CI [0.49, 1.57], P =.0002). Conclusion: The serum ADMA may be related to ischaemic stroke, and it is a risk factor for carotid atherosclerosis. [ABSTRACT FROM AUTHOR]

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is considered to be an immune-mediated heterogeneous disease involving cellular and humoral immunity. In recent years, autoantibodies against nodal/paranodal protein neurofascin155 (NF155), neurofascin186 (NF186), contactin-1 (CNTN1), and contactin-associated protein 1 (CASPR1) have been identified in a small subset of patients with CIDP, which disrupt axo-glial interactions at nodes/paranodes. Although CIDP electrodiagnosis was made in patients with anti-nodal/paranodal component autoantibodies, macrophage-induced demyelination, the characteristic of typical CIDP, was not observed. Apart from specific histopathology, the pathogenic mechanisms and clinical manifestations of CIDP with autoantibody are also distinct. We herein compared pathogenesis, histopathology, clinical manifestations, and therapeutic response in CIDP with autoantibody vs. CIDP without autoantibody. CIDP with autoantibodies should be considered as an independent disease entity, not a subtype of CIDP due to many differences. They possibly should be classified as CIDP-like chronic nodo-paranodopathy, which can better characterize these disorders, help diagnose and make the most effective therapeutic decisions. [ABSTRACT FROM AUTHOR]

• Cell replacement therapy is a strategy to achieve long-term motor improvements by preventing disease progression. • The cell sources mainly include fetal ventral mesencephalic tissue, embryonic stem cells, and induced pluripotent stem cells. • Extensive studies of fetal tissue implantation have led to the optimized transplantation process. • Embryonic stem cells have reliable isolation protocols and the potential to differentiate into dopaminergic progenitors. Parkinson's disease (PD) is characterized by tremor, rigidity, and bradykinesia. PD is caused mainly by depletion of the nigrostriatal pathway. Conventional medications such as levodopa are highly effective in the early stage of PD; however, these medications fail to prevent the underlying neurodegeneration. Cell replacement therapy (CRT) is a strategy to achieve long-term motor improvements by preventing or slowing disease progression. Replacement therapy can also increase the number of surviving dopaminergic neurons, an outcome confirmed by positron emission tomography and immunostaining. Several promising cell sources offer authentic and functional dopaminergic replacement neurons. These cell sources include fetal ventral mesencephalic tissue, embryonic stem cells (ESCs), neural stem cells (NSCs), mesenchymal stem cells (MSCs) from various tissues, induced pluripotent stem cells (iPSCs), and induced neural cells. To fully develop the potential of CRT, we need to recognize the advantages and limitations of these cell sources. For example, although fetal ventral midbrain is efficacious in some patients, its ethical issues and the existence of graft-induced dyskinesias (GID) have prevented its use in large-scale clinical applications. ESCs have reliable isolation protocols and the potential to differentiate into dopaminergic progenitors. iPSCs and induced neural cells are suitable for autologous grafting. Here we review milestone improvements and emerging sources for cell-based PD therapy to serve as a framework for clinicians and a key reference to develop replacement therapy for other neurological disorders. [ABSTRACT FROM AUTHOR]

Optical sparse aperture imaging technology has promising applications in the next generation of high-resolution imaging systems, but the phasing errors correction of sparse aperture is an urgent problem to be addressed. In this paper, we propose a blind structured-illumination super-resolution imaging system using a sparse aperture as the transmitter to overcome phasing errors and obtain higher resolution. In our scheme, an unknown pattern is projected onto the object by a sparse aperture system. By translating the unknown pattern, a sequence of modulated raw images is obtained. Based on these low-resolution raw images, the super-resolution object and the unknown illumination pattern are jointly estimated by the Adam algorithm. Here we show, both in the simulation and experiment, the resolution of reconstructions using sparse aperture as transmitter are similar to those using monolithic lens. Furthermore, we validate that the proposed method can protect the reconstruction effect from piston error and widen the tolerance range of tip/tilt error (peak-valley values) up to 0.5λ. At the same time, our proposed system can also alleviate to some extent the problem of mid-frequency modulation transfer function (MTF) attenuation that exists in sparse aperture imaging. Our approach not only simplifies the process of constructing synthetic aperture system, but also provides a novel application for synthetic aperture systems. • The introduction of structured illumination improves the resolution of synthetic aperture imaging. • Protect the reconstruction effect from piston error in the sparse aperture transmitter. • Widen the tolerance range for imaging system of tip/tilt error in sparse aperture transmitter. • Alleviate to some extent the problem of mid-frequency attenuation that exists in sparse aperture imaging. [ABSTRACT FROM AUTHOR]

Previous studies have shown that HE4 cancer biomarker promoted cancer cell proliferation and tumor growth in mouse xenograft models. Interestingly, HE4 levels are significantly increased in the seminal plasma of oligoasthenospermia patients, raising a question on HE4 role(s) in spermatogenesis. We constructed an HE4 overexpression mouse model (HE4-OE), and observed that HE4-OE male adult mice had small testes, low sperm counts, and elevated serum/testis testosterone levels. These mice exhibited disorganized seminiferous tubules and impaired spermatogenesis. HE4 overexpression concentrated in Leydig cells, and these cells had hyperplasia and increased testosterone biosynthesis. Mechanistic studies indicated that the impaired spermatogenesis was likely caused by a local and direct action of HE4 in the testis rather than by a hypothalamus/pituitary-initiated dysregulation. The new findings reveal a novel HE4 function in male reproductive system, and suggest the existence of a subtype of primary oligoasthenospermia characterized by HE4 overexpression, Leydig cell hyperplasia, and elevated testosterone levels. • Oligoasthenospermia patients exhibit increased levels of HE4 in seminal plasma. • Transgenic mice overexpressing HE4 have small testes, low sperm counts, and elevated serum/testis testosterone levels. • HE4 overexpressing mice exhibit disorganized seminiferous tubules, impaired spermatogenesis, and Leydig cell hyperplasia. • There might be a subtype of primary oligoasthenospermia manifesting as HE4 overexpression and Leydig cell hyperplasia. [ABSTRACT FROM AUTHOR]

This paper constructs a comprehensive evaluation system of human settlements focusing on housing conditions, urban natural environments, social economy, and public infrastructure. Principal Component Analysis and Cluster Analysis are used to analyze and rank the 2003–2013 human settlements index and create five clusters for 35 major cities in China (including municipalities, provincial capitals, and Prefecture-level cities). On the basis of four years of a spatial analysis of the human settlements index, we find that living conditions of 35 Chinese cities have significantly improved; severe air pollution persists in China, with large differences between the north and the south; weak correlation between urban human settlements and the growth rate of economic development; and the infrastructure of China's mega cities is overloaded. The results confirm and quantify growing geographic disparities and deep structural urban challenges that are associated with rapid economic growth and social change, leaving many cities in China to struggle with worsening pollution, excessive demand on existing infrastructures, and housing prices that rise faster than disposable incomes. [ABSTRACT FROM AUTHOR]

Background: Enolase 1 (ENO1) is a metabolic enzyme which participates in pyruvate synthesis and ATP production in cells. Previously, differential expression of ENO1 was discovered in villous tissues between recurrent miscarriage and induced abortion. This study was designed to explore whether ENO1 influences the proliferation and invasion of villous trophoblasts and the related molecular mechanisms. Methods: First, ENO1 expression in placental villus tissues collected from recurrent miscarriage (RM) patients and women for induced abortion as well as in trophoblast‐derived cell lines was detected by RT‐qPCR and western blotting. ENO1 localization and expression in villus tissues were further confirmed through immunohistochemistry staining. Then, the effects of ENO1 downregulation on trophoblast Bewo cell proliferation, migration, invasion, and epithelial‐mesenchymal transition (EMT) process were evaluated by CCK‐8 assay, transwell assay, and western blotting. As for the regulatory mechanism of ENO1, the expression of COX‐2, c‐Myc and cyclin D1 in Bewo cells after ENO1 knockdown was finally evaluated by RT‐qPCR and western blotting. Results: ENO1 was mainly localized in the cytoplasm, with very small amounts in the nucleus of trophoblast cells. ENO1 expression in the villi tissues of RM patients was significantly increased, when compared with the villous tissues of healthy controls. Furthermore, Bewo cells, a trophoblast cell line with relatively higher expression of ENO1, was used to downregulate the ENO1 expression by ENO1‐siRNA transfection. ENO1 knockdown significantly facilitated Bewo cell growth, EMT process, migration, and invasion. ENO1 silencing markedly elevated COX‐2, c‐Myc, and cyclin D1 expression. Conclusion: ENO1 may participate in the development of RM via suppressing the growth and invasion of villous trophoblasts via reducing the expression of COX‐2, c‐Myc, and cyclin D1. ENO1 may participate in the development of RM via suppressing the growth and invasion of villous trophoblasts via reducing the expression of COX‐2, c‐Myc, and cyclin D1. [ABSTRACT FROM AUTHOR]

Natural products have become sources of developing new drugs for the treatment of cancer. To seek candidate compounds that inhibit the growth of liver cancer, components of Chloranthus serratus were tested. Here, we report that shizukaol D, a dimeric sesquiterpene from Chloranthus serratus, exerted a growth inhibition effect on liver cancer cells in a dose- and time-dependent manner. We demonstrated that shizukaol D induced cells to undergo apoptosis. More importantly, shizukaol D attenuated Wnt signalling and reduced the expression of endogenous Wnt target genes, which resulted in decreased expression of β-catenin. Collectively, this study demonstrated that shizukaol D inhibited the growth of liver cancer cells by modulating Wnt pathway. [ABSTRACT FROM AUTHOR]

Aberrant expressions of some miRNAs were reported in the placenta from compromised pregnancies, suggesting that the miRNA profiling of chorionic villi could be related with early recurrent miscarriage (RM). This study was designed to investigate the miRNA expression profile, and to predict their potential target genes and signal pathways. The chorionic villi tissues were collected from 15 early RM cases and 15 controls. We focused on investigating the biological pathways and their potential functions in order to explore what is the likely association and how they are possibly involved in the development of early RM. The chorionic villi tissues were collected from 15 early RM cases and 15 controls. A total of 155 differentially expressed miRNAs over 2-fold changes in expression levels (P < 0.05), including 98 up-regulated and 57 down-regulated expressions. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the target genes of those miRNAs were mainly involved in the pathways of MAPK, B cell receptor, T cell receptor and tumor-associated signaling in the development of early RM. Those target genes of differentially expressed miRNAs, coupled with multiple biological processes and pathways, would be beneficial to understand the etiology and pathophysiological mechanism of early RM. [ABSTRACT FROM AUTHOR]

Background: Acute myeloid leukemia (AML) is a hematopoietic malignancy with poor outcomes, especially in older AML patients. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered a promising anticancer drug because it selectively induces the extrinsic apoptosis of tumor cells without affecting normal cells. However, clinical trials have shown that the responses of patients to TRAIL are significantly heterogeneous. It is necessary to explore predictable biomarkers for the preselection of AML patients with better responsiveness to TRAIL. Here, we investigated the critical role of tumor protein p53 inducible nuclear protein 2 (TP53INP2) in the AML cell response to TRAIL treatment. Methods: First, the relationship between TP53INP2 and the sensitivity of AML cells to TRAIL was determined by bioinformatics analysis of Cancer Cell Line Encyclopedia datasets, Cell Counting Kit-8 assays, flow cytometry (FCM) and cell line-derived xenograft (CDX) mouse models. Second, the mechanisms by which TP53INP2 participates in the response to TRAIL were analyzed by Western blot, ubiquitination, coimmunoprecipitation and immunofluorescence assays. Finally, the effect of TRAIL alone or in combination with the BCL-2 inhibitor venetoclax (VEN) on cell survival was explored using colony formation and FCM assays, and the effect on leukemogenesis was further investigated in a patient-derived xenograft (PDX) mouse model. Results: AML cells with high TP53INP2 expression were more sensitive to TRAIL in vitro and in vivo. Gain- and loss-of-function studies demonstrated that TP53INP2 significantly enhanced TRAIL-induced apoptosis, especially in AML cells with nucleophosmin 1 (NPM1) mutations. Mechanistically, cytoplasmic TP53INP2 maintained by mutant NPM1 functions as a scaffold bridging the ubiquitin ligase TRAF6 to caspase-8 (CASP 8), thereby promoting the ubiquitination and activation of the CASP 8 pathway. More importantly, simultaneously stimulating extrinsic and intrinsic apoptosis signaling pathways with TRAIL and VEN showed strong synergistic antileukemic activity in AML cells with high levels of TP53INP2. Conclusion: Our findings revealed that TP53INP2 is a predictor of responsiveness to TRAIL treatment and supported a potentially individualized therapeutic strategy for TP53INP2-positive AML patients. [ABSTRACT FROM AUTHOR]

Low acrosin activity (LAA) is associated with sperm function anomaly and poor outcomes of in vitro fertilization. In this study, we confirm that 993 semen samples with LAA had a reduced sperm motility and low in vitro fertilization rate in comparison with 1332 normal controls (NC). Proteomic comparison between 11 LAA and 11 NC sperm samples identified 35 upregulated and 99 downregulated proteins in the LAA group. Indeed, proteomic data showed that acrosome enzymes Spam1 and Acrosin were among the downregulated proteins in the LAA group, which was validated by quantitative PCR and immunefluorescent staining of sperm cells. The KEEG pathway analysis revealed a deficiency of GSH and Gln biosynthesis in LAA sperm cells. Immunofluorescent staining of sperms and quantitative PCR verified downregulation of GLUL and GCLC, the key enzymes for GSH and Gln biosynthesis. Moreover, the results of ELISA assay confirmed low levels of GSH and Gln in LAA sperm cells. Mechanistic studies showed that addition of 10 mM H2O2 to semen samples led to a significant reduction of acrosin activity and sperm motility, most possibly by triggering premature acrosome release. In contrast, the presence of 20 mM GSH blocked the oxidative effects of H2O2. Since GSH counteracts the oxidative stress and Gln participates in TCA cycling, their deficiency may affect the redox balance as well as energy production of sperm cells. These findings shed new light on the pathological mechanisms of infertility associated with LAA. Male infertility patients could benefit from GSH supplement by improvement of acrosin activity and other sperm functions. [ABSTRACT FROM AUTHOR]

As a means of chemical identification and analysis, Surface enhanced Raman spectroscopy (SERS), with the advantages of high sensitivity and selectivity, non-destructive, high repeatability and in situ detection etc., has important significance in the field of composition detection, environmental science, biological medicine etc. Physical model of coupling effect between different semiconductor substrates and noble metal particles were investigated by using 3D-FDTD method. Mechanism and the effects of excitation wavelength, particle spacing and semiconductor substrate types on the SERS effect were discussed. The results showed that the optimal excitation wavelengths of three noble metals of Ag, Au, Cu, were located at 510, 600 and 630 nm, respectively; SERS effect of Ag, Au, Cu increases with the decreasing of the inter distance of particles, while the distance of the NPs reaches the critical value of 3 nm, the strength of SERS effect will be greatly enhanced. For the four different types of substrate of Ge, Si, SiO 2 (glass) and Al 2 O 3 , the SERS effect of Ag on SiO 2 > Ge > Al 2 O 3 > Si. For Au and Cu nanoparticles, the SERS effect of them on oxide substrate is stronger than that on non-oxide substrate. In order to verify FDTD simulations, taking silver nanoparticles as an example, and silver nanoparticles prepared by chemical method were spinning coating on the four different substrates with R6G as probe molecules. The results show that the experimental results are consistent with FDTD theoretical simulations, and the SERS enhancement effect of Ag-SiO 2 substrate is best. The results of this study have important theoretical significance to explain the variations of SERS enhancement on different noble metals, which is also an important guide for the preparation of SERS substrates, especially for the microfluidics. The better Raman effect can be realized by choosing proper substrate type, particle spacing and excitation wavelength, result in expanding the depth and width of SERS application. [ABSTRACT FROM AUTHOR]

Ferroptosis is a form of cell death caused by the accumulation of lipid peroxidation products due to abnormal iron metabolism. However, it remains unknown whether ferroptosis participates in the process of radiation-induced ovarian injury. Sphingosine-1-phosphate (S1P) is an important bioactive sphingolipid that has a protective effect on ovarian injury. The present study aims to determine whether X-ray radiation induces ferroptosis in the ovarian granulosa KGN cell line, and explore the potential effect of S1P and its mechanism in radiation-induced ferroptosis. The results indicated that irradiation reduced the viability of KGN cells, altered the mitochondrial morphology, induced the intracellular accumulation of iron ions, increased oxidative stress, and induced lipid peroxidation. Furthermore, the radiation exposure triggered the ferroptosis in KGN cells. S1P can alleviate radiation-induced ferroptosis. Furthermore, the protective effect of S1P was reversed after the application of siRNA to interfere with the glutathione peroxidase 4 expression. Ferroptosis might be pervasive in radiation-induced ovarian injury, and S1P may serve as a potential therapeutic approach to protect against the toxic effect of radiation in female gonads by inhibiting ferroptosis. [Display omitted] • Ferroptosis might be pervasive in radiation-induced ovarian injury. • S1P could alleviate radiation-induced ferroptosis. • The effect of S1P was reversed after GPX4 silencing. • S1P may be a therapeutic approach to protect against the toxic effect of radiation on female gonads. [ABSTRACT FROM AUTHOR]

To investigate the relationship between ovulation and pregnancy outcomes in patients undergoing intrauterine insemination (IUI). The clinical data from 784 patients, diagnosed with polycystic ovarian syndrome (PCOS) or unexplained infertility, underwent 1624 IUI cycles were analyzed retrospectively. Ovulation was observed by transvaginal ultrasonography on the day of IUI. The clinical pregnancy rate (CPR), abortion rate (AR), and live birth rate (LBR) were analyzed. The study included 1031 pre-ovulation IUI cycles (63.49%) and 593 post-ovulation IUI cycles (36.51%). The CPR was 13.05%, the AR was 15.57%, and the LBR was 11.02%. Ovulation before or after IUI affected the CPR (11.06% VS 16.53%, p =.002) and LBR (9.41% VS 13.83%, p =.006) per cycle, but did not affect the AR (14.91% VS 16.33%, p =.149). The sex ratio of children was not related to ovulation (p =.948). After adjusting for baseline characteristics and logistic regression, the CPR (OR = 1.931, 95% CI 1.062–1.931, p =.019) and LBR (OR = 1.389, 95% CI 1.007–1.916, p =.045) of post-ovulation insemination were higher than those of pre-ovulation insemination significantly. Pregnancy outcomes were affected by ovulation on the day of IUI in patients with unexplained infertility or PCOS. Post-ovulation insemination may improve the CPR of IUI. [ABSTRACT FROM AUTHOR]

• BPTF promotes epithelial-mesenchymal transition in trophoblast cells. • BPTF inhibits E-cadherin expression. • BPTF transcriptionally activates Slug. The trophoblast epithelial-to-mesenchymal transition (EMT) is a procedure related to embryo implantation, spiral artery establishment and fetal-maternal communication, which is a key event for successful pregnancy. Inadequate EMT is one of the pathological mechanisms of recurrent miscarriage (RM). Whole-exome sequencing revealed that the mutation of bromodomain PHD-finger transcription factor (BPTF) was strongly associated with RM. In the present study, the effects of BPTF on EMT and the underlying mechanism were investigated. We found that the expression of BPTF in the villi of RM patients was significantly downregulated. Gene Ontology (GO) analysis revealed that BPTF participated in cell adhesion. The knockdown of BPTF prevented EMT and attenuated trophoblast invasion in vitro. BPTF activated Slug transcription by binding directly to the promoter region of the Slug gene. Interestingly, the protein levels of both Slug and BPTF were decreased in the villous cytotrophoblasts (VCTs) of RM villi. In conclusion, BPTF participates in the regulation of trophoblast EMT by activating Slug expression, suggesting that BPTF defects are an important factor in RM pathogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Multidrug resistance (MDR) to anticancer drugs is a major obstacle to successful chemotherapy in the treatment of cancers. Identification of natural compounds capable of circumventing MDR with minimal adverse side effects is an attractive goal. Here, we found that H6, a gypenoside aglycon from Gynostemma pentaphyllum, displayed potent anti-MDR activity. Average resistant fold (RF) of H6 is 1.03 and 1.04 in KB/VCR and MCF-7/ADR cells compared to their parental cells. H6 alone ranging from 2μmol/l to 40μmol/l (μM) did not display a significant anti-proliferative effect on KB/VCR cells and other cells, while the compound at these concentrations enhanced the cytotoxicity of vincristine (VCR) to KB/VCR cells. H6 showed a significant synergistic effect in combination with VCR. By quantification of sub-G1 fraction cells, H6 also enhanced the VCR-induced apoptosis in a dose-dependent manner. The short time treatment with H6 increased the intracellular accumulation of rhodamine 123 (Rho123) and 5(6)-carboxyfluorescein diacetate (CFDA) in KB/VCR cells. Further studies showed that H6 treatment resulted in the decrease of the RNA transcript level of P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP). H6 inhibited the function of P-gp by stimulating P-gp ATPase activity and decreased MRP1 expression with a blockade of STAT3 phosphorylation. These findings suggest that H6, a multi-targets reversal agent with no significant toxic effect, may be a potential candidate to circumvent the P-gp and MRP1-mediated MDR. [Copyright &y& Elsevier]

Zero-dimensional carbon nanomaterials show intriguing potential in the field of unconventional oil resource development for reducing injection pressure and enhancing oil recovery. However, the complicated synthesis procedure, necessity for surfactant and limited understanding of the mechanism impede their practical applications. In this study, novel high-hydrophilic carbon dots (hh -CDs) with an average particle size of 2.54 ± 0.016 nm were facilely synthesized through an electrochemical approach by employing cost-effective petroleum coke as the carbon source, followed by treating with ozone for further oxidation. The abundant surface functional groups render hh -CDs superior hydrophilicity, dispersibility and stability. Core flooding tests show 0.20 wt% hh -CDs nanofluid delivers a prominent pressure-reducing rate of 23.81% and an enhancement in oil recovery of 26.38% without any surfactant. Analytical results of atomic force microscope (AFM) with hydrophobic probe reveal hh -CDs can adsorb on the rock surface to alter the micro-scale wettability from oil-wet to homogeneous water-wet. The hh -CDs can also efficiently reduce the core surface roughness and afford excess disjoining pressure for oil displacement, accounting for the impressive performance. This work provides a feasible oil systemic circulation for the synthesis of versatile surfactant-free carbon dots for boosting injection pressure reduction and enhancing oil recovery in tight oil reservoirs. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: The pathophysiological mechanism of recurrent miscarriage (RM) is unclear. The goals of this study were to determine the role of microRNA-4497 overexpression in placental villus tissues in early RM; To identify the potential target mRNAs of miRNA-4497; And to investigate the microRNA-4497-mediated regulatory mechanisms in placental trophoblasts. Methods: Bioinformatics analysis was performed to identify the candidate target genes of miRNA-4497. The protein expression of Sp1 transcription factor (SP1), chemokine (C-X-C motif) receptor 5 (CXCR5) and bone morphogenetic protein 8a (BMP8A) were determined in the villus tissues of the RM and normal groups by Western blotting and immunohistochemistry. Cultured 293T cells were co-transfected with the miRNA-4497 agomir or luciferase reporter vectors containing the wild-type or mutant 3'-UTRs of the target mRNAs to verify the regulatory role of miRNA-4497. Results: Bioinformatics analysis suggested that SP1, CXCR5 and BMP8A mRNAs are potential targets of miRNA-4497. The expression of SP1, CXCR5 and BMP8A proteins in the chorionic villus tissues of RM placentas were significantly decreased compared to those in the normal controls. Moreover, SP1 protein levels were inversely correlated with the levels of miRNA-4497 in the placentas of RM patients and normal controls. The expression of SP1 mRNA and protein were down-regulated in HTR-8/SVneo cells after forced overexpression of the miRNA-4497 agomir. The results of the co-transfection assay showed that mutation of the miRNA-4497-binding sites in the 3'-untranslated region (3'-UTR) of SP1 led to a recovery of luciferase activity upon overexpression of miRNA-4497, suggesting that SP1 could be a direct target of miRNA-4497. Conclusions: An increased miRNA-4497 level in the placental villus tissues associated with recurrent miscarriage may down-regulate SP1 expression. The negative regulation of SP1 by miRNA-4497 may potentially contribute to the pathogenesis of recurrent miscarriage through promotion of trophoblast apoptosis. These findings provide novel information on the regulation of placental trophoblast apoptosis, and could be useful for the development of new therapeutic strategies for better management of recurrent miscarriage. [ABSTRACT FROM AUTHOR]

Fatty acid oxidation of cumulus-oocyte complex (COC) provides sufficient energy for oocyte maturation. But, the relationship between fatty acid oxidation and oxidative stress in aging follicles, as well as the effect of putrescine, is still unclear. The porcine COCs were randomly divided into four groups and cultured in in vitro maturation (IVM) medium with or without 1 mmol/L putrescine, with 50 μmol/L hydrogen peroxide (H 2 O 2) or with 50 μmol/L H 2 O 2 plus 1 mmol/L putrescine. Oocyte maturation was assessed by the first polar body extrusion. The expressions of genes involved in fatty acid oxidation were detected, and the mitochondrial function was analyzed by themembrane potential. The maturation rate of oocyte was significantly lower in the H 2 O 2 group when compared with the control group (P ＜0.001), and putrescine significantly increased this rate in the H 2 O 2 plus putrescine group when compared with the H 2 O 2 group (P ＜0.001). The expressions of LKB1, STRAD, ACC2, AMPKα1 and AMPKα2 mRNAs in cumulus cells (CCs) were significantly downregulated by H 2 O 2 treatment, and partly rescued by putrescine addition (P ＜0.05–0.001). However, the changes of LKB1, STRAD, ACC2, AMPKα1 and AMPKα2 mRNAs in oocytes were inapparent. The mitochondrial membrane potential of CCs in the H 2 O 2 group was significantly lower than that in the control group, while putrescine addition significantly increased the mitochondrial membrane potential (P ＜0.001). The decrease of oocyte maturation due to oxidative stress is related with the decreased fatty acid oxidation, and putrescine may alleviate the COCs damage via improving fatty acid oxidation. • Fatty acid oxidation of cumulus-oocyte complex provides sufficient energy for oocyte maturation. • The decrease of oocyte maturation due to oxidative stress is related with the decreased fatty acid oxidation. • Putrescine may alleviate the cumulus-oocyte complex damage via improving fatty acid oxidation. [ABSTRACT FROM AUTHOR]

• City-level agricultural production efficiency is mapped by Super-Efficiency Data Envelopment Analysis model. • The agricultural production efficiency is featured as spatial agglomerations. • The OLS and GWR models are used to explore the spatial heterogeneity and driving mechanisms of agricultural production efficiency. • Series of policy recommendations are provided. The level of agricultural production efficiency (APE) affects farmers' livelihood decisions and the transformation and reconstruction of the rural territorial system. This paper constructs an evaluation index system of China's APE from the perspective of input–output. The spatial autocorrelation model and econometric model are used to calculate the spatio-temporal evolution characteristics and influencing factors of China's APE in 1990 and 2017. The results show that China's APE level is relatively low, and there are significant spatial differences. The extremely high efficiency regions are distributed in the eastern plains of China; the regions with extremely low efficiency are mainly distributed in the southwest and the western regions of China. The results of the spatial correlation effect show that the H-H agglomeration regions of APE are usually distributed in the eastern coastal areas and northeastern areas, while the L-L agglomeration regions are mainly distributed in the central mountainous areas and the border areas of western Yunnan. From 1990 to 2017, the influencing factors of APE have gradually changed, and showing a more complex trend, mainly including farmland management scale , multiple crop index, rural per capita net income, population density, and precipitation per unit area. Finally, the corresponding policy and suggestions are provided. [ABSTRACT FROM AUTHOR]

Surface-enhanced Raman spectroscopy (SERS) has the potential to detect pesticide residues in agricultural products. However, some systemic pesticides, such as chlorpyrifos, can enter the plant tissue, and not just stay on the surface. Consequently, many SERS studies halted at practical application because of its complexity. In this work, SERS technology was used to detect chlorpyrifos residues in tea products at the semiquantitative level. A simple pretreatment method effectively avoided interference of other fluorescent substances, and all major peaks could be distinguished on the basis of a novel substrate. A principal component analysis algorithm was applied to form a regression model, and a nanogram detection limit was obtained. Furthermore, chlorpyrifos residues in the same tea products were also measured by gas chromatography–mass spectrometry, and the results show a small range of errors. From the comparative study of the two detection methods, the results suggest the great promise of SERS technology for rapid inspection of agricultural products. [ABSTRACT FROM AUTHOR]

Abstract It is of great significance to timely, accurately, and effectively monitor land use/cover in city regions for the reasonable development and utilization of urban land resources. The remotely sensed dynamic monitoring of Land use/land cover (LULC) in rapidly developing city regions has increasingly depended on remote-sensing data at high temporal and spatial resolutions. However, due to the influence of revisiting periods and weather, it is difficult to acquire enough time-series images with high quality at both high temporal and spatial resolution from the same sensor. In this paper we used the temporal-spatial fusion model ESTARFM (Enhanced Spatial and Temporal Adaptive Reflectance Fusion Model) to blend Landsat8 and MODIS data and obtain time-series Landsat8 images. Then, land cover information is extracted using an object-based classification method. In this study, the proposed method is validated by a case study of the Changsha City. The results show that the overall accuracy and Kappa coefficient were 94.38% and 0.88, respectively, and the user/producer accuracies of vegetation types were all over 85%. Our approach provides an accurate and efficient technical method for the effective extraction of land use/cover information in the highly heterogeneous regions. [ABSTRACT FROM AUTHOR]

Abstract: A visible‐light‐induced trifluoromethylation of isonitrile‐substituted indole derivatives has been developed from the reaction of isonitrile‐substituted indoles with Togni II reagent, affording 1‐(trifluoromethyl)‐4,9‐dihydro‐3H‐pyrido[3,4‐b]indoles in moderate to good yields. The further transformations to β‐carboline derivatives and a harmacine derivative have been performed, demonstrating the potential synthetic utility of this method. A preliminary biological study indicated that the CF3‐containing harmine analogue significantly stimulated the secretion of glucagon‐like peptide‐1 (GLP‐1), suggesting an improvement in treating diabetes. [ABSTRACT FROM AUTHOR]

Next-generation sequencing of the exome and genome of prostate cancers has identified numerous genetic alternations. SPOP (Speckle-type POZ Protein) was one of the most frequently mutated genes in primary prostate cancer, suggesting SPOP is a potential driver of prostate cancer development and progression. However, how SPOP mutations contribute to prostate cancer pathogenesis remains poorly understood. SPOP acts as an adaptor protein of the CUL3-RBX1 E3 ubiquitin ligase complex that generally recruits substrates for ubiquitination and subsequent degradation. ER-localized isoform of the formin protein inverted formin 2 (INF2) mediates actin polymerization at ER-mitochondria intersections and facilitates DRP1 recruitment to mitochondria, which is a critical step in mitochondrial fission. Here, we revealed that SPOP recognizes a Ser/Thr (S/T)-rich motif in the C-terminal region of INF2 and triggers atypical polyubiquitination of INF2. These ubiquitination modifications do not lead to INF2 instability, but rather reduces INF2 localization in ER and mitochondrially associated DRP1 puncta formation, therefore abrogates its ability to facilitate mitochondrial fission. INF2 mutant escaping from SPOP-mediated ubiquitination is more potent in prompting mitochondrial fission. Moreover, prostate cancer-associated SPOP mutants increase INF2 localization in ER and promote mitochondrial fission, probably through a dominant-negative effect to inhibit endogenous SPOP. Moreover, INF2 is important for SPOP inactivation-induced prostate cancer cell migration and invasion. These findings reveal novel molecular events underlying the regulation of INF2 function and localization, and provided insights in understanding the relationship between SPOP mutations and dysregulation of mitochondrial dynamics in prostate cancer. [ABSTRACT FROM AUTHOR]

Miscarriage is the spontaneous loss of a pregnancy before the fetus reaching viability, including all pregnancy losses from the time of conception until 24 weeks of gestation. Three or more times of consecutive spontaneous miscarriages is defined as recurrent miscarriage (RM). The underlying causes cannot be confirmed in nearly 50% of RM patients. We investigated the differential expression of long noncoding RNAs (lncRNAs) in chorionic villi tissues of RM patients compared with normal women, and their possible involvement in the pathogenic pathways leading to RM. A total number of 1449 differentially expressed lncRNAs were identified from chorionic villi tissues of RM patients compared to normal women. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis revealed that these differentially expressed lncRNAs were involved in 26 biological pathways including 11 up-regulated and 15 down-regulated ones. Functional analysis showed that pathways of endocrine, immunity, ECM-receptor interactions and apoptosis are the major pathogenic mechanisms involved in the development of RM. Characterization of these lncRNAs in different pathways opened a new starting point for further investigating the epigenetic regulation mechanisms of lncRNAs in RM. [ABSTRACT FROM AUTHOR]

Aurora B is a serine/threonine kinase that has a key role in mitosis and is overexpressed in cancer cells. Aberrations in Aurora B are highly correlated with tumorigenesis and cancer development, so many studies have focused on the development of Aurora B kinase inhibitors. Based on one of our previous high-throughput screening studies, we identified lead compound S6, a small-molecule benzofuran derivative that binds Aurora B and inhibits its kinase activity in vitro . S6 also displayed high selectivity for Aurora B inhibition. The cytotoxicity of S6 was assessed against a panel of 21 cancer cell lines. The cervical cancer cell line HeLa, liver cancer cell line HepG2 and colon cancer cell line SW620 were the most sensitive to S6 treatment. We found that S6 decreased the proliferation and colony formation of these three cell lines and elevated their percentages of cells in the G2/M phase of the cell cycle. S6 also inhibited phospho-histone H3 on Ser 10, a natural biomarker of endogenous Aurora B activity. The growth suppression of liver cancer QGY-7401 xenograft tumors was observed in nude mice after S6 administration, and this effect was accompanied by the in vivo inhibition of phospho-histone H3 (Ser 10). Taken together, we conclude that targeting Aurora B with compound S6 may be a novel strategy for cancer treatment, and additional studies are warranted. [ABSTRACT FROM AUTHOR]

Abstract: Several families of kinases work together to ensure the rate and precision of mitosis. Aurora-B is an important serine/threonine kinase required for chromosome segregation and cytokinesis. Identification of Aurora-B substrates will help to enhance our understanding of the molecular mechanism of mitosis. Through a yeast two-hybrid screen, we found a novel partner of Aurora-B, Septin1, belonging to a conserved family of GTPase proteins that localize to the cleavage furrow and are involved in cytokinesis. We confirmed this interaction using Co-immunoprecipitation experiments in mammalian cells and GST-pull-down analysis in vitro. Moreover, Aurora-B can phosphorylate Septin1 in vitro. We identified that Ser248, Ser307, and Ser315 are the main phosphorylation sites in Septin1. These two proteins partially co-localize to the midbody during cytokinesis. So, it is possible that Septin1’s role in the regulation of cytokinesis is related to its phosphorylation by Aurora-B. Unlike previous reports that Septins function in cytokinesis and localize to the cleavage furrow, we found that Septin1 localizes to the spindle pole throughout mitosis, indicating that Septin1 may function in chromosome segregation as well. [Copyright &y& Elsevier]

Abstract: The Reticulon (RTN) family of proteins is thought to play important roles in the regulation of neuronal regeneration. In this study, we have identified a novel alternative splicing isoform of the RTN gene family, RTN3-A1, which contains an additional 2.3-kb exon. The transcripts of human and mouse RTN3-A1 (about 5.0 kb) were first discovered by database sequence mining and analysis, and verified by cloning and sequencing. Northern blot analysis of 16 human tissues with a common probe of RTN3 transcripts and a specific probe for RTN3-A1 demonstrated that human RTN3-A1 is expressed mainly in brain tissues with a weak expression in the skeletal muscle. With Western blot analysis, the expected 100-kDa RTN3-A1 protein was detected in mouse brain. In situ hybridization with a mouse RTN3-A1-specific cRNA probe revealed that the mouse RTN3-A1 mRNA was regionally expressed in the neurons of the cerebral cortex, hippocampus, hypothalamus, and cerebellum of the adult mouse brain. In contrast to the transcripts of RTN1 and RTN2, RTN3-A1 shares some significant similarity with RTN4-A in exon structure, tissue distribution, and brain expression profile. Since other reports have shown that RTN4-A inhibits neuronal outgrowth and restricts the plasticity of the central nervous system, we speculate that RTN3-A1 might play certain roles in the central nervous system. [Copyright &y& Elsevier]

A stable substrate is extraordinarily important for the trace detection of Surface Enhanced Raman Scattering technique. We have designed in this paper a simple seed growth method to prepare Ag@ZrO 2 core-shell nanoparticles as well as regulate the core-shell ratio by adjusted concentration of zirconium propoxides added. The shell thickness effect and spacing on SERS activities have been simulated in different finite time domains, which goes perfectly with those previous experiment results. With Ag@ZrO 2 core-shell nanoparticles adopted as the SERS substrate and R6G as molecular probe, the detection range could reach as great as 10-8 M. The regression model, obtained through principal component analysis, is adopted for some rapid and precise detection; and the determination coefficient (R2) is going up to 0.9743, proving that the SERS substrate we have prepared has extremely high detection accuracy. To explore the stability of core-shell nanoparticles, we have taken both two different cases of strong acid solution as well as strong alkali solution for the core-shell nanoparticle etching, and this is how a SERS test could be carried out. These experimental results have indicated that the outer zirconia layer could keep the silver surface from oxidation and its stability is ensured, quite crucial for the applied SERS. Image 1 • Simple seed growth method to prepare Ag@ZrO 2 core-shell nanoparticles is proposed. • The reliability of the Ag@ZrO 2 core-shell nanoparticles immersed in strong acid and strong alkali solution. • Ag@ZrO 2 adopted as the SERS substrate, the LOD of R6G could reach as great as 10-8 M. [ABSTRACT FROM AUTHOR]