Irritable bowel syndrome (IBS) is a common disorder in gastrointestinal system and impairs the quality of life of the patients. Clostridium butyricum (CB) is a probiotics that has been used in ...several gastrointestinal diseases. The efficacy of CB in treating IBS is still unknown. This prospective, multi-centre, randomized, double-blind, placebo-controlled trial aimed to assess the efficacy and safety of CB in treating diarrhea-predominant IBS (IBS-D) and analyze the fecal microbiota after treatment. Two hundred patients with IBS-D were recruited and were given CB or placebo for 4 weeks. End points included change from baseline in IBS symptoms, quality of life, stool consistency and frequency. Compared with placebo, CB is effective in improving the overall IBS-D symptoms (-62.12 ± 74.00 vs. -40.74 ± 63.67, P = 0.038) as well as quality of life (7.232 ± 14.06 vs. 3.159 ± 11.73, P = 0.032) and stool frequency (-1.602 ± 1.416 vs. -1.086 ± 1.644, P = 0.035). The responder rates are found higher in CB compared with the placebo (44.76% vs. 30.53%, P = 0.042). The change in fecal microbiota was analyzed and function pathways of CB in treating IBS-D were predicted. In conclusion, CB improves overall symptoms, quality of life and stool frequency in IBS-D patients and is considered to be used as a probiotics in treating IBS-D clinically.
STUDY QUESTION
What mechanism is involved in regulating the autophagy of endometrial stromal cells (ESCs), and does it participate in the pathogenesis of endometriosis?
SUMMARY ANSWER
CXCL12 ...down-regulates secretory phase ESC autophagy.
WHAT IS KNOWN ALREADY
mTOR (mammalian target of rapamycin), the major negative regulator of autophagy, is abnormally increased in endometriotic lesions and is involved in the direct regulation of endometrial stromal cell (ESC) apoptosis.
STUDY DESIGN, SIZE, DURATION
Autophagy was measured by transmission electron microscopy and immunofluorescence, and in vitro analysis was used to measure estrogen/CXCL12/CXCR4 signaling-mediated ESC autophagy.
PARTICIPANTS/MATERIALS, SETTING, METHODS
A total of 31 controls and 31 women with histologically confirmed endometriosis were included. We measured the autophagy level of normal and endometriosis-derived endometrium, and its relationship to the stage of endometriosis, as well as the potential molecular and signaling pathways that mediate the aberrant autophagy in endometriosis.
MAIN RESULTS AND THE ROLE OF CHANCE
Compared with control secretory phase ESCs, a significant reduction of the autophagy grade (as observed in TEM), punctuate LC3B staining (as observed in immunofluorescence assays), and autophagy-associated protein levels were exhibited in secretory phase eutopic ESCs (P < 0.05) and ectopic ESCs (P < 0.05) from women with endometriosis. In addition, the autophagy level was strongly negatively correlated with the CXCL12 concentration in ESCs (R2 = −0.9694). However, there was no significant difference in autophagy grade or CXCL12 concentration between stage I–II and stage III–IV endometriosis-derived ectopic ESCs (P > 0.05). Based on a human autophagy PCR array, CXCL12 and CXCR4, which is the CXCL12 receptor, in ESCs were predicted to be molecules that mediate the abnormally lower autophagy in endometriosis. Accordingly, after estradiol (E2) treatment a marked increase in CXCL12 secretion (1.71-fold, P < 0.01) and CXCR4 expression (5.07-fold, P < 0.01) in secretory phase ESCs was observed together with decreases in autophagy grade (TEM), punctuate LC3B immunofluorescent staining and autophagy-associated protein levels (P < 0.05). These changes could be reversed by progesterone (P4) (P < 0.05). The suppression of autophagy induced by E2 and recombinant human CXCL12 protein could be abrogated by an anti-CXCR4 neutralizing antibody and by a NF-κB inhibitor (P < 0.05), respectively. In addition, estrogen-stimulated CXCL12 secretion led to a low population of S phase cells (P < 0.05), as well as a low level of apoptosis (P < 0.05) in secretory phase ESCs.
LIMITATIONS, REASONS FOR CAUTION
Further studies are needed to examine the mechanism of autophagy on ESC apoptosis.
WIDER IMPLICATIONS OF THE FINDINGS
Measures to increase in endometrial autophagy might be a valid, novel approach to reduce local E2-dependent growth of endometriotic tissue.
STUDY FUNDING/COMPETING INTEREST(S)
This study was supported by the National Natural Science Foundation of China (NSFC) (81471513, 81471548 and 81270677), the Training Program for Young Talents of Shanghai Health System XYQ2013104, the Program for Zhuoxue of Fudan University, and the Program for Creative Talents Education of Key Disciplines of Fudan University. None of the authors has any conflict of interest to declare.
Intrinsically low conductivity and poor reactivity restrict many semiconductors from electrochemical detection. Usually, metal- and carbon-based modifications of semiconductors are necessary, making ...them complex, expensive, and unstable. Here, for the first time, we present a surface-electronic-state-modulation-based concept applied to semiconductors. This concept enables pure semiconductors to be directly available for ultrasensitive electrochemical detection of heavy-metal ions without any modifications. As an example, a defective single-crystalline (001) TiO2 nanosheet exhibits high electrochemical performance toward Hg(II), including a sensitivity of 270.83 μA μM–1 cm–2 and a detection limit of 0.017 μM, which is lower than the safety standard (0.03 μM) of drinking water established by the World Health Organization (WHO). It has been confirmed that the surface oxygen vacancy adsorbs an O2 molecule while the Ti3+ donates an electron, forming the O2 •– species that facilitate adsorption of Hg(II) and serve as active sites for electron transfer. These findings not only extend the electrochemical sensing applications of pure semiconductors but also stimulate new opportunities for investigating atom-level electrochemical behaviors of semiconductors by surface electronic-state modulation.
Due to the nature of domains, ferroics, including ferromagnetic, ferroelectric, and ferroelastic materials, exhibit hysteresis phenomena with respect to external driving fields (magnetic field, ...electric field, or stress). In principle, every ferroic material has its own hysteresis loop, like a fingerprint, which contains information related to its properties and structures. For ferroelectrics, many characteristic parameters, such as coercive field, spontaneous, and remnant polarizations can be directly extracted from the hysteresis loops. Furthermore, many impact factors, including the effect of materials (grain size and grain boundary, phase and phase boundary, doping, anisotropy, thickness), aging (with and without poling), and measurement conditions (applied field amplitude, fatigue, frequency, temperature, stress), can affect the hysteretic behaviors of the ferroelectrics. In this feature article, we will first give the background of the ferroic materials and multiferroics, with an emphasis on ferroelectrics. Then it is followed by an introduction of the characterizing techniques for the loops, including the polarization–electric field loops and strain–electric field curves. A caution is made to avoid misinterpretation of the loops due to the existence of conductivity. Based on their morphologic features, the hysteresis loops are categorized to four groups and the corresponding material usages are introduced. The impact factors on the hysteresis loops are discussed based on recent developments in ferroelectric and related materials. It is suggested that decoding the fingerprint of loops in ferroelectrics is feasible and the comprehension of the material properties and structures through the hysteresis loops is established.
Western and East Asian people hold fundamentally different beliefs about learning that influence how they approach child rearing and education. Reviewing decades of research, Dr Jin Li presents an ...important conceptual distinction between the Western mind model and the East Asian virtue model of learning. The former aims to cultivate the mind to understand the world, whereas the latter prioritizes the self to be perfected morally and socially. Tracing the cultural origins of the two large intellectual traditions, Li details how each model manifests itself in the psychology of the learning process, learning affect, regard of one's learning peers, expression of what one knows and parents' guiding efforts. Despite today's accelerated cultural exchange, these learning models do not diminish but endure.
Although polymer electrolyte membrane fuel cells （PEMFCs） have received broad attention due to their virtually zero emission, high power density, and high efficiency, at present the limited stability ...of the electrocatalysts used in PEMFCs is a critical limitation to their large-scale commercialization. As a type of popularly used electrocatalyst material, carbon black supported platinum （Pt/C）--although highly efficient--undergoes corrosion of carbon, Pt dissolution, Ostwald ripening, and aggregation of Pt nanoparticles （NPs） under harsh chemical and electro- chemical oxidation conditions, which results in performance degradation of the electrocatalysts. In order to overcome these disadvantages, many groups have tried to improve the carbon support materials on which Pt is loaded. It has been found that some novel carbon nanomaterials and noncarbon materials with high surface areas, sufficient anchoring sites, high electrical conductivities, and high oxidation resistance under the strongly oxidizing condition in PEMFCs are ideal alternative supports. This review highlights the following aspects： （i） Recent advances in using novel carbon nanomaterials and noncarbon support materials to enhance the long-term durability of electrocatalysts; （ii） solutions to improve the electrical conductivity, surface area, and the strong interaction between metal and supports; and （iii） the synergistic effects in hybrid supports which help improve the stability of electrocatalysts.
Immune system evasion, distance tumor metastases, and increased cell proliferation are the main reasons for the progression of non-small cell lung cancer (NSCLC) and the death of NSCLC patients. ...Dysregulation of circular RNAs plays a critical role in the progression of NSCLC; therefore, further understanding the biological mechanisms of abnormally expressed circRNAs is critical to discovering novel, promising therapeutic targets for NSCLC treatment.
The expression of circular RNA fibroblast growth factor receptor 1 (circFGFR1) in NSCLC tissues, paired nontumor tissues, and cell lines was detected by RT-qPCR. The role of circFGFR1 in NSCLC progression was assessed both in vitro by CCK-8, clonal formation, wound healing, and Matrigel Transwell assays and in vivo by a subcutaneous tumor mouse assay. In vivo circRNA precipitation, RNA immunoprecipitation, and luciferase reporter assays were performed to explore the interaction between circFGFR1 and miR-381-3p.
Here, we report that circFGFR1 is upregulated in NSCLC tissues, and circFGFR1 expression is associated with deleterious clinicopathological characteristics and poor prognoses for NSCLC patients. Forced circFGFR1 expression promoted the migration, invasion, proliferation, and immune evasion of NSCLC cells. Mechanistically, circFGFR1 could directly interact with miR-381-3p and subsequently act as a miRNA sponge to upregulate the expression of the miR-381-3p target gene C-X-C motif chemokine receptor 4 (CXCR4), which promoted NSCLC progression and resistance to anti-programmed cell death 1 (PD-1)- based therapy.
Taken together, our results suggest the critical role of circFGFR1 in the proliferation, migration, invasion, and immune evasion abilities of NSCLC cells and provide a new perspective on circRNAs during NSCLC progression.
Exosomes contain cell-specific collections of bioactive materials including proteins, lipids, and RNAs that are transported to recipient cells to exert their impacts. MicroRNAs (miRNAs) can function ...as tumor suppressor or oncogenic genes and miR-21 is one of the most frequently up-regulated miRNAs in solid tumors including colon cancer. The aim of this study was to investigate the role of miR-21, secreted from exosomes, in proliferation and invasion of colon cancer, along with the mechanistic details. We used a variety of biochemical techniques including ultracentrifugation-based exosome purification, electron transmission microscopy, western blot and RT-qPCR to detect the expression levels of miR-21 in exosomes purified from culture media of human colonic adenocarcinoma cell lines. We then performed functional and mechanistic studies using three colon cancer cell lines HT29, T84 and LS174 as well as the normal colon epithelial cells CRL1831. miR-21 target PDCD4 was investigated for its role in mediating miR-21 effects. Expression of miR-21 was significantly up-regulated in exosomes of colon cancer cells, compared to the normal human colon epithelial cells. Treatment of colon cancer cells with isolated exosomes or miR-21 led to an increased expression of genes involved in cell proliferation, invasion and extracellular matrix formation. miR-21 targets PDCD4, TPM1 and PTEN were down-regulated by exosomes and silencing of PDCD4 mimicked miR-21 functional effects, even the induced resistance against 5-FU. Our study suggests that targeted inhibition of exosomes, particularly those carrying miR-21, may represent a novel approach for treatment of colorectal cancer.
Identifying genomic variation is a crucial step for unraveling the relationship between genotype and phenotype and can yield important insights into human diseases. Prevailing methods rely on ...cost-intensive whole-genome sequencing (WGS) or whole-exome sequencing (WES) approaches while the identification of genomic variants from often existing RNA sequencing (RNA-seq) data remains a challenge because of the intrinsic complexity in the transcriptome. Here, we present a highly accurate approach termed SNPiR to identify SNPs in RNA-seq data. We applied SNPiR to RNA-seq data of samples for which WGS and WES data are also available and achieved high specificity and sensitivity. Of the SNPs called from the RNA-seq data, >98% were also identified by WGS or WES. Over 70% of all expressed coding variants were identified from RNA-seq, and comparable numbers of exonic variants were identified in RNA-seq and WES. Despite our method’s limitation in detecting variants in expressed regions only, our results demonstrate that SNPiR outperforms current state-of-the-art approaches for variant detection from RNA-seq data and offers a cost-effective and reliable alternative for SNP discovery.
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Oily water treatment has become an urgent need in our daily life because of its harmful potential to the ecological system. In recent years, functional materials with superwetting or ...superantiwetting property have experienced a rocketing development due to their applications in various areas, including self-cleaning, anti-icing, printing, water collection, liquid transfer, oil/water separation, and so on. In this regard, recent advances in polymer science hold the promise of fine-tuning the composition and morphology for a targeted design to meet the requirements in specific application fields. This review focused on polymeric materials, especially smart polymers, for controllable oil/water separations. Starting from the fundamental theories and criteria related to the separation mechanisms, different stimuli including pH, solvent, ions, chemicals, temperature, photo, electric, pressure, and dual stimuli for triggering smart oil/water separation processes were summarized. Highlights on polymer types, polymer synthesis approaches, separation materials fabrication method, as well as separation performances were present. Current limitations and future perspective were also given. This review aims to offer deep insights into polymer-based interfacial science and provide guidance for the fabrication of smart polymeric surfaces for oily water separation.
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