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The ErbB receptor family, including the epidermal growth factor receptor (EGFR) and ErbB2/3/4, regulate cell proliferation, differentiation, apoptosis, motility, etc., and their abnormalities can cause cancer and other diseases. Ligand-induced endocytosis of ErbB receptors is the key to various cancer treatment strategies, and different techniques have been developed to study this important process. Among them, single particle tracking (SPT) can reveal the spatiotemporal heterogeneity of ErbB receptors on the live cell membrane and has been used to characterize the EGFR dimerization process. Herein, we studied the endocytosis dynamics of two different ErbB receptors using dark-field microscopy. With anti-ErbB modified plasmonic gold nanorods (AuNRs) as probes, we compared the trajectories of individual anti-EGFR AuNRs (cAuNRs) and anti-ErbB AuNRs (tAuNRs) interacting with MCF-7 cells in situ in real time. The results revealed that the internalization rate of cAuNRs was faster than that of tAuNRs. Detailed SPT analysis suggests that cAuNRs enter cells through EGFR endocytosis pathway, and multiple intracellular transport modes sort the cAuNRs away from the transmembrane site. In contrast, the endocytosis resistance of ErbB2 slows down the cellular uptake rate of tAuNRs and causes some tAuNRs-ErbB2 complexes to be confined on the membrane with "circular" and "rolling circle" motions for a much longer time. Our results provide insights into the endocytosis process of the ErbB receptor family at the nanometer scale and could be potentially useful to develop cancer treatment strategies.

Long noncoding RNAs (lncRNAs) are increasingly recognized as functional regulators of human cancers. BRAF-activated noncoding RNA (BANCR), an oncogenic lncRNA, has a carcinogenic effect on many types of cancers. However, the clinical significance and molecular mechanisms of BANCR in cervical cancer are still unclear. Here, we generated BANCR knockout cell lines

Sepsis is an acute life-threatening disorder associated with multiorgan dysfunction that remains the leading cause of death in intensive care units. As sepsis progresses, it causes prolonged immunosuppression, which results in sustained mortality, morbidity, and susceptibility to secondary infections. Using a mouse model of sepsis, we found that the long noncoding RNA HOTAIRM1 (HOXA transcript antisense RNA myeloid-specific 1) was highly expressed in mice during the late phase of sepsis. The upregulation of HOTAIRM1 was induced by Notch/Hes1 activation and, moreover, was critical for the formation of an immunosuppressive microenvironment. HOTAIRM1 induced T cell exhaustion by increasing the percentage of PD-1+ T cells and regulatory T cells, accompanied by elevated PD-L1. Blockade of either Notch/Hes1 signaling or HOTAIRM1 inhibited T cell exhaustion in late sepsis, having alleviated lung injury and improved survival of mice. Further mechanistic studies identified HOXA1 as a key transcription factor targeted by HOTAIRM1 to regulate PD-L1 expression in lung alveolar epithelial cells. These results implicated that the Notch/Hes1/HOTAIRM1/HOXA1/PD-L1 axis was critical for sepsis-induced immunosuppression and could be a potential target for sepsis therapies.

In this paper, two cationic probes 1a and 1b and a neutral dye 1c were successfully designed and synthesized according to the Knoevenagel condensation reaction, which combines the good optical properties of hemocyanine and the biocompatibility of nitrogen-containing heterocyclic rings based on a quinoxaline skeleton. Probes 1a and 1b showed an OFF-ON fluorescence response to nucleic acids with excellent selectivity. Specifically, the fluorescence intensity of probe 1a was enhanced by 18 and 133 times, respectively, along with the increase of DNA or RNA concentrations (0-600 μg mL

Polarity and viscosity, as important microenvironment parameters, play an essential role in cell metabolism. Therefore, 9-acridine carboxaldehyde reacted with cyano compounds to obtain polarity-sensitive probes 1a-b and viscosity-sensitive probes 1c-d. Among them, with the increase in solvent polarity, the maximum emission wavelength of acridine-dicyanoisophorone-based probe 1a red-shifted from 553 nm to 594 nm, the fluorescence quantum yield increased from 0.5% to 35.6%, and the fluorescence intensity enhanced 38 fold. The acridine-cyanofuranone based probe 1b also has a polarity response similar to 1a. Nevertheless, when the solution viscosity increased from 0.89 cP (100% water) to 856 cP (1% water), the fluorescence intensity of the acridine-tricyanodihydrofuran based probe 1c at 430 nm enhanced 5.6 times. The acridine-cyanobenzothiazole based probe 1d also had a viscosity response similar to 1c. In addition, probes 1a-b were used for further HeLa cell imaging experiments due to their good photostability and the results suggested that probe 1a could locate lipid droplets and probes 1b-c could stain lysosomes. Moreover, probes 1a-b could dynamically monitor the changes in intracellular polarity.

A series of viscosity sensitive fluorescent probes 1a-e were synthesized by linking coumarin and oxazolopyridinium via dimethylene in this paper. The viscosity test of probes 1a-e indicated that the fluorescence intensity of the probes enhanced significantly with the increase of viscosity of the system (0.89-865 cP), and exhibited a nearly OFF-ON response to viscosity at 648 nm, 650 nm and 650 nm, respectively. In addition, cells still had a high survival rate after co-culturing with probes 1a-e for 12 h (94-98%). Meanwhile, the laser confocal experiment showed that the variation of the carbon chain length in the oxazolopyridinium could affect the subcellular region of the localization of the probes in cells. When the length of the carbon chain in oxazolopyridinium was between n-C7H15 and n-C12H23, probes 1b-d had the ability to target the endoplasmic reticulum in the cells. Moreover, probes 1b-d showed no significant change in fluorescence intensity after 35 min of continuous laser confocal irradiation, indicating that they had excellent anti-photobleaching properties.

To develop a new class of neutral fluorescent dyes with mitochondrial staining capacity, a series of functional dyes were obtained from Nile Red (2a–e) and coumarin (3a–e) with different amide compounds via Suzuki coupling reactions. The Nile Red derivatives (2a–e) emitted red fluorescence (590–660 nm) and coumarin derivatives (3a–e) showed blue emission (455–490 nm) in organic solvents. In addition, they exhibited high fluorescence quantum yields (0.27–0.98) in organic solvents and excellent photostability (>92%). Moreover, all of them possessed low cytotoxicity. More importantly, Nile Red borate (2) and coumarin borate (3) only accumulated in lipid droplets, while after being modified by different amide compounds, dyes 2a–e and 3a–e could successfully target mitochondria in HeLa cancer cells via confocal fluorescence experiments. This work provides a new strategy for the design of neutral cellular probes for mitochondrial staining.

Background:. Minimal change nephropathy (MCD) is a common pathological type of nephrotic syndrome and is often associated with acute kidney injury (AKI). This study aimed to investigate the clinical characteristics and related factors of AKI in patients with MCD and nephrotic syndrome. Methods:. Patients from Chinese People's Liberation Army General Hospital who were diagnosed with pathological renal MCD with clinical manifestations of nephrotic syndrome were included from January 1, 2013 to December 31, 2017. Patients diagnosed with membranous nephropathy (MN) by renal biopsy from January 1, 2013 to December 31, 2017 are included as a control population. We retrospectively analyzed the clinical and pathological characteristics of patients as well as the percentages and clinical characteristics of AKI in different age groups. We assessed the correlation of pathological characteristics with serum creatinine using multivariate linear regression analysis. Results:. A total of 367 patients with MCD were included in the analysis, with a sex ratio of 1.46: 1 (male: female) and an age range of 6 to 77 years. Among all the patients, 109 developed AKI (29.7%), and of these patients, 85 were male (78.0%). In the 586 patients with MN, 27 (4.6%) patients developed AKI. The percentage of AKI in MCD patients was significantly higher than that in MN patients (χ2 = 41.063, P

BackgroundCircular RNAs (CircRNAs) are biologically active RNAs. CDR1as is one such circRNA previously reported to be a microRNA-7 (miR-7) sponge, thereby regulating associated gene expression. The specific underlying molecular mechanisms of CDR1as biology, however, remain largely unknown.MethodsWe performed CDR1as knockdown in order to explore its function in cell proliferation, migration, the cell cycle, and tumorigenesis. We further employed quantitative proteomic analyses and associated bioinformatics strategies to globally assess CDR1as-regulated proteins (CRPs). Western blotting and immunofluorescence staining were used to validate the proteomic results. We additionally investigated a specific link between TMED2, TMED10, and miR-7 via a dual-luciferase reporter system, and generated CDR1as knockout cell lines via CRISPR/Cas9 editing.ResultsWe identified 353 proteins dysregulated upon CDR1as knockdown in 293 T cells. These CRPs were found to interact with one another and to play key roles in certain cellular pathways. Two such proteins, TMED2 and TMED10, were found to specifically contribute to the influence of CDR1as on cell proliferation. CDR1as may regulate these two TMED proteins through miR-7 sponging. We were able to further confirm these results using both CRISPRi cell lines and nude mouse models.ConclusionThis study suggested that CDR1as may regulate cell proliferation via serving as a miR-7 sponge, thereby regulating TMED2 and TMED10 expression. These results are an invaluable template for future streamlined studies of circRNAs.

Six mitochondria/lysosomes self-targetable and viscosity-sensitive dyes (1a–1f) were developed via simple structure modification on cyanine-derived dyes. They all showed remarkable OFF–ON fluoresce...

The Notch signaling pathway is mainly involved in the regulation of neural stem cell proliferation, survival and differentiation during the development of the central nervous system. As a neurodevelopmental disorder, autism is associated with an abnormal increase in the number of microglia in several brain regions. These findings suggest that the pathogenesis of autism may be related to the Notch signaling pathway and microglia. In this review, we discuss how Notch pathway activity leads to behavioral abnormalities such as learning and memory impairment by influencing neuronal biological activities. An increase in microglial protein synthesis and abnormal autophagy can affect synaptic development and lead to behavioral abnormalities, and all of these changes can lead to autism. Furthermore, the Notch signaling pathway regulates the activation and differentiation of microglia and promotes inflammatory responses, leading to the occurrence of autism. When excessive reactive oxygen species (ROS) secreted by microglia cannot be cleared by autophagy in a timely manner, Notch signaling pathway activity is affected, possibly further increasing susceptibility to autism. This review reveals the mechanism underlying the role of the Notch signaling pathway, microglia and their interaction in the pathogenesis of autism and provides a theoretical reference for targeted clinical therapies for autism.

To analyze the correlation of the sperm DNA fragmentation index (DFI) level with semen parameters and pregnancy outcomes of artificial insemination of the husband (AIH) in the cycle of intrauterine insemination (IUI).We collected the clinical data on 777 cases of IUI, including female clinical indicators, male semen parameters, sperm DFI and pregnancy outcomes. According to the DFI level, we divided the patients into three groups: DFI15%, 15% ≤ DFI30% and DFI ≥ 30%.The sperm DFI level was significantly elevated with the increased age of the males (P = 0.002) and closely related to the total number of motile sperm (P = 0.002) and total sperm motility (P = 0.000) before treatment, as well as to sperm concentration (P = 0.000), total sperm motility (P = 0.001) and total number of progressively motile sperm (P = 0.000) after density gradient centrifugation. The rate of clinical pregnancy was decreased in the DFI ≥ 30% group. There were no statistically significant differences between sperm DFI and the rates of clinical pregnancy and abortion.Male age significantly affects the sperm DFI level. Sperm DFI is closely related to sperm motility and total number of progressively motile sperm, but not to the rates of clinical pregnancy and abortion in patients undergoing IUI. IUI can be used as an effective method of assisted reproduction for male infertility./.

An increasing number of men are fathering children at an older age than in the past. While advanced maternal age has long been recognized as a risk factor for adverse reproductive outcomes, the influence of paternal age on reproduction is incompletely comprehended. Herein, we found that miR‐125a‐5p was upregulated in the sperm of aging males and was related to inferior sperm DNA integrity as an adverse predictor. Moreover, we demonstrated that miR‐125a‐5p suppressed mitochondrial function and increased cellular DNA damage in GC2 cells. We also found that miR‐125a‐5p perturbed embryo development at specific morula/blastocyst stages. Mechanistically, we confirmed that miR‐125a‐5p disturbed the mitochondrial function by targeting Rbm38 and activating the p53 damage response pathway, and induced a developmental delay in a p21‐dependent manner. Our study revealed an important role of miR‐125a‐5p in sperm function and early embryo development of aging males, and provided a fresh view to comprehend the aging process in sperm., miR‐125a‐5p was increased in the sperm of aging males. miR‐125a‐5p suppressed mitochondrial function and increased cellular DNA damage by targeting Rbm38 and activating p53 damage response pathway. miR‐125a‐5p perturbed embryo development at specific morula/blastocyst stages in a p21‐dependent manner.

Sulfur dioxide (SO2) plays an extremely important role in the basic processes of physiology and pathology. As an antioxidant, SO2 can maintain the redox homeostasis in the cell. Excessive inhalation of SO2 would lead to irreparable respiratory damage, resulting in respiratory diseases, neurological disorders, and even cardiovascular disease. Thus, it is urgent to exploit an excellent way to monitor SO2 derivatives in biological system. Herein, we design a water-soluble ratiometric fluorescent probe to fast detect the level of SO2 derivatives in living cells in vivo. The probe displays obvious fluorescence signal at long wavelength, which is helpful for imaging of biological system. After respond to SO2 derivatives, the fluorescence signal at 465 nm increases rapidly due to the Michael addition reaction is triggered, further causing the disruption of large conjugated system. The probe exhibits high selectivity and fast respond to SO2 derivatives, which can be able to sensitive and real-time monitoring of SO2 derivatives level in living cells. Moreover, the probe reveals a low detection limit and a great linear relationship to SO2 derivatives. Based on the negligible cytotoxicity and good biocompatibility of the probe, which is employed to detect exogenous and endogenous SO2 derivatives in living cells. In addition, it is also served as a potential chemical tool to detect SO2 derivatives in mice model of sinusitis.

Colorectal cancer (CRC) is one of the leading causes of death worldwide, and hence, there is a need to elucidate the molecular mechanisms contributing to the progression of CRC. In this study, we aimed at assessing the role of long non‐coding RNA NBPF4 on the tumorigenesis of CRC. Silencing or overexpression experiments were performed on HCT116 and SW260 in vitro models. BALB/c athymic female nude mice aged 5–6 weeks were used as in vivo models. To assess the relationship between NBPF4 and its regulatory RNA pull‐down assay, RNA immunoprecipitation, luciferase activity, Western blotting and qRT‐PCR were employed. Initially, we identified that NBPF4 was downregulated in CRC tissues and cell lines. Furthermore, we observed that NBPF4 decreased tumorigenesis in both in vitro and in vivo models. Additionally, we identified that ETFA was highly expressed in CRCs and was negatively associated with NBPF4. Subsequently, we identified that EZH2, a transcriptional factor, activated ETFA by enhancing the methylation of its promoter, and EZH2 was also highly regulated in CRCs. Using COAD and READ databases, we confirmed that EZH2 and ETFA were positively correlated. Furthermore, we identified NBPF4 and EZH2 were targets for ZFP36, which bound and positively regulated NBPF4. This prevented NBPF4 from binding to its negative regulator miR‐17‐3p. Our results demonstrated that NBPF4 downregulated EZH2 and stabilized itself by binding to ZFP36, thus escaping from inhibition by miR‐17‐3p, which allowed mitigation of CRC through inhibition of ETFA.

Three hydrogen sulfide (H2S) probes based on an azonia–cyanine skeleton were successfully designed and prepared. Probe 1a, containing 4-chloro-7-nitro-1,2,3-benzoxadiazole connected to the cyanine dye, had an emission at 660 nm that was enhanced 4.5-fold by the reduced photoinduced electron transfer process when reacting with H2S. Probes 1b and 1c were constructed from cyanine dyes with electron withdrawing 2,4-dinitrophenyl and 7-nitrobenzo[c] [1,2,5]oxadiazol-4-yl groups, respectively. Probes 1b and 1c gave off−on type responses with 169- and 17-fold fluorescent enhancements at 639 nm with H2S. Their emission properties were influenced by intramolecular hydrogen bonds and intramolecular charge transfer processes. The detection limits of probes 1a–1c were calculated at 178, 121, and 9.6 nM, respectively. The intracellular imaging experiments with HeLa cells indicated probe 1a was a mitochondria-targeting H2S probe, while probes 1b and 1c were lysosome-targeting H2S probes.

Reactions of the phosphanyl-gold(I) precursor [(AuCl)2(bdppmapy)] (1; bdppmapy = N,N-bis(diphenylphosphanylmethyl)-2-aminopyridine) with Na2S in a 1:1 or 1:2 molar ratio gave rise to one tetradecanuclear and one octanuclear Au(I) sulfido cluster, [Au14S6(bdppmapy)5]Cl2 (2) and [Au18S8(bdppmapy)6]Cl2 (3), respectively. The former displays a new structural framework in gold cluster chemistry. Compounds 2 and 3 showed strong green luminescence and were employed as excellent imaging probes to selectively light up the lysosomes of living cells. Their long-term tracking of lysosomes can be achieved for up to 36 h, while tracking with commercial Lyso-Tracker Red under the same conditions was limited to 3 h. Our work demonstrated the possibility of constructing novel gold(I) sulfido clusters supported by special P-N hybrid ligands and the potential application of these clusters as long-term selective trackers of lysosomes in bioimaging.

(1) To establish appropriate FRAIL-NH cutoff points in nursing homes in Mainland China; (2) To compare the FRAIL-NH scale and Frailty Index in assessing frailty prevalence and associated factors in nursing homes.A cross-sectional study.Six nursing homes in Changsha, China.A total of 302 residents aged 60 years or older (mean aged 82.71±8.49, 71.2% female).Frailty was assessed using the 34-item Frailty Index and the FRAIL-NH scale.The appropriate FRAIL-NH cutoff points to classify frail status and frailest status were 1.5 (87.6% sensitivity, 63.3% specificity) and 7.5 (94.1% sensitivity, 73.4% specificity), respectively. Based on the FRAIL-NH and Frailty Index, 69.5% (48% for frail and 21.5% for frailest), and 66.5% (60.9% for frail and 5.6% for frailest) of residents were at risk of frailty, respectively. There was no statistically significant difference in the total frailty prevalence assessed by FRAIL-NH and Frailty Index (χ2=0.617, P=0.432). The FRAIL-NH Scale is significantly associated with the Frailty Index (correlation coefficient (r) = 0.74, P0.001), but there was a Kappa agreement of 0.39 for frailty classification between the FRAIL-NH and Frailty Index, with the Frailty Index classifying a larger number of individuals as frail. When using FRAIL-NH scale, disease and self-reported health status were associated with frail and frailest status while age was just associated with frailest status. regarding the Frailty Index, age, diseases, medications and self-reported health status were associated with frail and frailest status.The FRAIL-NH is a simple and effective tool to assess the overall frailty rate in nursing homes, and the Frailty Index may be more suitable capturing the multidimensionality of frailty at an individual level. Careful consideration in the selection of a frailty instrument, based on the intended purpose, is necessary.

Imaging RNA-protein interaction in the cellular space with single molecule sensitivity is attractive for studying gene expression and regulation, but remains a challenge. In this study, we reported a photoactivatable trimolecular fluorescence complementation (TriFC) system based on fluorescent protein, mIrisFP, to identify and visualize RNA-protein interactions in living mammalian cells. We also combined this TriFC system with photoactivated localization microscopy (PALM), named the TriFC-PALM technique, which allowed us to image the RNA-protein interactions with single molecule sensitivity. Using this TriFC-PALM technique, we identified the actin-bundling protein, FSCN1, specifically interacting with the HOX Transcript Antisense RNA (HOTAIR). The TriFC-PALM imaging acquired a higher resolution compared with the traditional method of total internal reflection (TIRF) imaging. The TriFC-PALM thus provides a useful tool for imaging and identifying the RNA-protein interactions inside cells at the nanometer scale.

Five cyanine dyes (6a-e) with aza units were prepared by the reaction of pyridinum or quinolinium with suitable aldehydes. They present several remarkable features including large Stokes shift (235–282 nm), long emission wavelength (640–698 nm) and excellent selectivity. Moreover, probes 6a-b display obvious and sensitive fluorescent response to DNA and RNA in aqueous solution, and the quantum yield of probe 6a response to RNA increases from 0 to 8.9%. More importantly, probes 6c and 6e can effectively avoid DNA interference and only respond to RNA in aqueous solution. In addition, laser confocal cell experiment has showed that probe 6b can image the nucleolus of nucleic acids in HeLa cells.

Analyzing the diffusional dynamics of nanoparticles on cell membrane plays a significant role in better understanding the cellular uptake process and provides a theoretical basis for the rational design of nano-medicine delivery. Single particle tracking (SPT) analysis could probe the position and orientation of individual nanoparticles on cell membrane, and reveal their translational and rotational states. Here, we show how to use traditional dark-field microscopy to monitor the dynamics of gold nanorods (AuNRs) on live cell membrane. We also show how to extract the location and orientation of AuNRs using ImageJ and MATLAB, and how to characterize the diffusive states of AuNRs. Statistical analysis of hundreds of particles show that single AuNRs perform Brownian motion on the surface of U87 MG cell membrane. However, individual long trajectory analysis shows that AuNRs have two distinctly different types of motion states on the membrane, namely long-range transport and limited-area confinement. Our SPT methods can be potentially used to study the surface or intracellular particle diffusion in different biological cells and can become a powerful tool for investigations of complex cellular mechanisms.

Background Previous research and published literature indicate that some patients with spinal diseases who underwent percutaneous transforaminal endoscopic decompression (PTED) still suffer some discomfort in the early recovery stage in the form of pain, stiffness, and swelling. These are usually considered minor residual symptoms or normal postoperative phenomenon (NPF) in the clinic, occur frequently, and are acknowledged by surgeons worldwide. To the best of our knowledge, we report the first case of a patient who had an osteoporotic vertebral fracture (OVF) misdiagnosed as NPF after she underwent PTED as a result of lumbar disc herniation (LDH). Case presentation A 71-year-old female with Parkinson’s disease who presented with lower back pain radiating to the legs was diagnosed as LDH in L4–5, after which a PTED of L4–5 was performed, with temporary alleviation of symptoms. However, severe lower back pain recurred. Unfortunately, the recurred pain initially misdiagnosed as NPF, in fact, was finally confirmed to be OVF by CT-scan. OVF in the early stage of post-PTED seldom occurs and is rarely reported in the literature. With a percutaneous vertebroplasty, the pain was significantly relieved, and she resumed walking. After 36-weeks of follow-up, the pain improved satisfactorily. Conclusion Doctors should not immediately diagnose a relapse of back pain following PTED as NPF, and hands-on careful physical and imaging examinations are necessary to manage recurring pain rightly and timely.

In human conversations, the emergence of new topics is a key factor in enabling dialogues to last longer. Additional information brought by new topics can make the conversation more diverse and interesting. Chat-bots also need to be equipped with this ability to proactively elicit new chatting topics. However, previous studies have neglected the elicitation of new topics in open-domain conversations. At the same time, previous works have represented topics with word-level keywords or entities. However, a topic is open to multiple keywords and a keyword can reflect multiple potential topics. To move towards a fine-grained topic representation, we represent topic with topically related words. In this paper, we design a novel model, named CMTE, which focuses not only on coherence with context, but also brings up new chatting topics. In order to extract topic information from conversational utterances, a Topic Fetcher module is designed to fetch semantic-coherent topics with the help of topic model. To equip model with the ability to elicit new topics, a Topic Manager module is designed to associate the new topic with context. Finally, responses are generated by a well-designed fusion decoding mechanism to explicitly distinguish between topic words and general words. Experiment results show that our model is better than state of the art in automatic metrics and manual evaluations.

Photodynamic therapy (PDT) has been successfully applied in clinical treatment several years. However, after finished treatment process the residual photosensitizer will spread throughout body, which forces patients stay in the dark room to avoid exposure in sunlight several weeks. Therefore, develop degradable photosensitizer could effectively eliminate this inconvenience. In the past, researchers have developed degradable photosensitizers based on supramolecular structure. In this study, we achieved the same effect in small molecule level. Three thiocarbonyl photosensitizers (PS) have high photogenerated

Accumulating evidence suggests that radiation treatment causes an adaptive response of lung adenocarcinoma (LUAD), which in turn attenuates the lethal effect of the irradiation. Previous microarray assays manifested the change of gene expression profile after irradiation. Bioinformatics analysis of the significantly changed genes revealed that VANGL1 may notably influence the effect of radiation on LUAD. To determine the role of VANGL1, this study knocked down or overexpressed VANGL1 in LUAD. M6A level of VANGL1 mRNA was determined by M6A-IP-qPCR assay. Irradiation caused the up-regulation of VANGL1 with the increase of VANGL1 m6A level. Depletion of m6A readers, IGF2BP2/3, undermined VANGL1 mRNA stability and expression upon irradiation. miR-29b-3p expression was decreased by irradiation, however VANGL1 is a target of miR-29b-3p which was identified by Luciferase report assay. The reduction of miR-29b-3p inhibited the degradation of VANGL1 mRNA. Knockdown of VANGL1 enhanced the detrimental effect of irradiation on LUAD, as indicated by more severe DNA damage and increased percentage of apoptotic cells. Immunocoprecipitation revealed the interaction between VANGL1 with BRAF. VANGL1 increased BRAF probably through suppressing the protein degradation, which led to the increase of BRAF downstream effectors, TP53BP1 and RAD51. These effectors are involved in DNA repair after the damage. In summary, irradiation caused the up-regulation of VANGL1, which, in turn, mitigated the detrimental effect of irradiation on LUAD by protecting DNA from damage probably through activating BRAF/TP53BP1/RAD51 cascades. Increased m6A level of VANGL1 and reduced miR-29b-3p took the responsibility of VANGL1 overexpression upon irradiation.

Background Virtual reality (VR) is the use of computer technology to create an interactive three-dimensional (3D) world, which gives users a sense of spatial presence. In nursing education, VR has been used to help optimize teaching and learning processes. Objective The purpose of this study was to evaluate the effectiveness of VR in nursing education in the areas of knowledge, skills, satisfaction, confidence, and performance time. Methods We conducted a meta-analysis of the effectiveness of VR in nursing education based on the Cochrane methodology. An electronic literature search using the Cochrane Library, Web of Science, PubMed, Embase, and CINAHL (Cumulative Index to Nursing and Allied Health Literature), up to December 2019 was conducted to identify studies that reported the effectiveness of VR on knowledge, skills, satisfaction, confidence, and performance time. The study selection and data extraction were carried out by two independent reviewers. The methodological quality of the selected studies was determined using the Cochrane criteria for risk-of-bias assessment. Results A total of 12 studies, including 821 participants, were selected for the final analysis. We found that VR was more effective than the control conditions in improving knowledge (standard mean difference [SMD]=0.58, 95% CI 0.41-0.75, P Conclusions The results of this study suggest that VR can effectively improve knowledge in nursing education, but it was not more effective than other education methods in areas of skills, satisfaction, confidence, and performance time. Further rigorous studies with a larger sample size are warranted to confirm these results.

Bacterial biofilms widely exist in nature and seriously threaten global public health. Biofilms always cause persistent infection and seriously aggravate the occurrence of antibiotic resistance, which makes the treatment of bacterial infection difficult. Current conventional therapies, such as antibiotics, bacteriophages and quorum sensing inhibitors, are widely used to combat biofilms. However, these therapies are inadequate for the safe and effective treatment of biofilms. Antibiotics often produce resistance in treated bacteria, and antibacterial peptides are easily decomposed by proteases, so their efficacy is reduced. These results indicate that the treatment of biofilms needs further improvement. Increasing evidence has shown that natural medicine therapies have significant inhibitory effects on biofilms. This review summarized and analyzed the efficacy characteristics and corresponding mechanisms of conventional and natural medicine therapies combatting biofilms. By comparison, the advantages and disadvantages of those therapies have been classified and interpreted, so we have inferred that combined medication with natural medicines will be a more effective strategy against biofilms. This review lays a promising foundation for the development of antibiofilm agents and provides novel thinking for the treatment of bacterial biofilm infections.

Four different neutral fluorescent markers containing nitrogen heterocycles (quinoxaline, 1H-pyrazolo[3,4-b]pyridine, 1H-indazole and 1H-pyrrolo[2,3-b]pyridine) as targeting groups were designed and prepared in order to screen out structural units for targeting mitochondria. Several classical fluorophores (coumarin, 1,8-naphthalimide and Nile Red) were connected with these heterocycles via Suzuki coupling reactions. The derivatives of coumarin (dyes 1a and 2a–c) and 1,8-naphthalimide (dyes 3a–c) fluoresced in the blue-green region, while the Nile Red derivatives (dyes 1b and 4a–c) fluoresced in the red light region. The optical properties of the classical fluorophores, such as emission properties and photostability, were retained in the new dyes. All of them showed low cytotoxicity. Confocal fluorescence experiments in L929 normal cells and HeLa cancer cells indicated that dyes 1a–b targeted dual sites of mitochondria and lipid droplets. Moreover, dyes 2a–c, 3a–c and 4a–c targeted mitochondria; meanwhile, there are only a few mitochondria-targeting markers with neutral skeletons. Furthermore, it was found that nitrogen heterocycles with N–H bonds can improve the mitochondrial targeting ability of partial neutral fluorophores.

In order to improve lysosome targetability of probes, fluorescent probes based on benzo[a]phenoxazine attaching different length oligoethyleneoxy chains were designed and prepared. Probes 2a–c containing N-pyridineium-3-yl exhibited almost ON-OFF near-infrared emission responses at 697–701 nm from pH 2.8 to 7.2, and the calculated pKa values of 2a–c were 4.90, 4.92 and 5.03 respectively. More importantly, fluorescent imaging experiments indicated that probes 2a–c were all lysosome biomarkers for Ges-1 and HeLa cells, which was because the introduction of oligoethyleneoxy groups improved the biocompatibility of probes, so that the probes 2a–c were better transported to lysosomes via the endocytosis pathway of the cells. Moreover, the probe 2a was selected as a representative, which not only showed good reversibility and selectivity, but used to successfully image lysosomal pH increases induced by chloroquine.

Background Anastomotic leak after esophagectomy is one of the most challenging complications resulting in a high morbidity and mortality and prolonged hospitalization. The aim of this retrospective study was to access the impact of endoscopy intervention in anastomotic leak. Methods A retrospective review was conducted at our hospital from January 2008 to December 2016. In total, 263 patients who were diagnosed with an anastomotic leak after esophagectomy and underwent endoscopy examination were included in this study. First, all patients were divided into two groups based on a single criteria—whether they received endoscopy intervention or not—and comparisons were conducted between the two groups. Second, we categorized all patients into three groups based on the diameter of the anastomotic leak (group I: 15 mm). Detailed analyses were made for each group. Factors we considered included demographic factors, the length of postoperative hospital stay, the amount of medical expenditure, limited days of oral intake, and the incurrence of complications. Data relating to those factors were collected and then analyzed using standard statistic tools. Results In general, the difference between endoscopy intervention and conservative measure was significant. Moreover, the hospital stay (p Conclusions Endoscopy intervention is safe and effective in the diagnosis and treatment of postesophagectomy anastomotic leak. Especially for patients with a diameter of anastomotic leaks greater than 5 mm, the advantages of endoscopy intervention should not be neglected.

Sulforaphene (SFE), a natural isothiocyanate from cruciferous vegetables has shown a potential anticancer effect against cervical and lung cancer. Palliative treatments like photodynamic therapy (PDT) are being implemented for a long time however, the results are still not promising in case of aggressive cancers like anaplastic thyroid cancer. The objective of this work is to establish an alternative method with the combination of photofrin-PDT and sulforaphene, a natural isothiocyanate from cruciferous vegetables, against human anaplastic thyroid cancer to enhance the efficacy of PDT. In this study, cell viability of FRO cells due to combination treatment was analyzed by MTT assay, Cell cycle arrest, MMP depolarization and ROS generation, analyzed by flow cytometry. Western blot analysis of various proliferative proteins was performed to assess the activity of combination treatment against FRO cells. From the results, sulforaphene alone showed no cytotoxicity against normal cells, however, combination of sulforaphene and photofrin mediated PDT showed a noticeable decrease in cell proliferation against FRO cells. Combination treatment synergistically caused cell cycle arrest via ROS generation and MMP depolarization. The expressions of Ras, MEK, ERK, B-Raf proteins significantly modulated due to combination treatment. PDT and SFE can induce apoptosis in anaplastic thyroid cancer cells individually but while treated in combination, it enhanced the apoptotic and anti-proliferative effect, much higher than the individual doses. In summary, our work designates sulforaphene as a unique natural enhancer of efficacy with PDT against anaplastic thyroid cancer.

Long noncoding RNA HOX transcript antisense RNA (HOTAIR) is involved in human tumorigenesis and is dysregulated in hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying HOTAIR functions in HCC are largely unknown. Here, we employed an integrated transcriptomic and quantitative proteomic analysis to systematically explore the regulatory role of HOTAIR in HCC. A total of 673 transcripts and 293 proteins were found to be dysregulated after HOTAIR inhibition. Bioinformatics studies indicated that differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) are involved in many biological processes, especially cancer-related signaling pathways. A set of DEGs and DEPs were validated by quantitative RT-PCR, Western blot and parallel reaction monitoring (PRM) analysis, respectively. Further functional studies of the opioid growth factor receptor (OGFr), a negative biological regulator of cell proliferation in HCC, revealed that HOTAIR exerts its effects on cell proliferation, at least in part, through the regulation of OGFr expression. By correlating the omics data with functional studies, the current results provide novel insights into the functional mechanisms of HOTAIR in HCC cells.

The trend towards efficient and intensive use of land resources is an inevitable outcome of current social development. The rational matching of urban land prices and land use intensity has become an important factor under accelerating urbanization, and promotes the healthy development of the social economy. Using data on residential land price and on land use intensity for 31 provinces and cities in China, we employ the E-G cointegration test and quadrant map classification to determine the coordination relationship between land price and land use intensity. We then employ HR coordination to calculate the coordination degree of land price and land use intensity, and classify the coordination type accordingly. Our results are as follows. (1) The spatio-temporal distribution of urban land price shows high variability with multiple maxima, and follows a decreasing trend from the southeast coastal area to the northwest inland area and the northeast. (2) The overall land use intensity is at or above the middle level, and shows large spatial differences between provinces, but the agglomeration between provinces is increasing. (3) From the perspective of the relationship between urban land price and land use intensity at the inter-provincial scale, we find that the land price and land use intensity are well coordinated, and the number of provinces has been dynamically changing during different development periods. There is an east-west difference in the spatial distribution of land price and land use intensity coordination level. Different provinces and cities with the same coordination stage show differences in their land price and land use intensity level.

The authors determined that HOTAIR specifically bind to YBX1 and promote its nuclear translocation, and then regulating cell proliferation by stimulating the PI3K/Akt and ERK/RSK signaling pathways., HOTAIR is a long noncoding RNA (lncRNA) which serves as an important factor regulating diverse processes linked with cancer development. Here, we used comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-MS) to explore the HOTAIR-protein interactome. We were able to identify 348 proteins interacting with HOTAIR, allowing us to establish a heavily interconnected HOTAIR-protein interaction network. We further developed a novel near-infrared fluorescent protein (iRFP)-trimolecular fluorescence complementation (TriFC) system to assess the interaction between HOTAIR and its interacting proteins. Then, we determined that HOTAIR specifically binds to YBX1, promotes YBX1 nuclear translocation, and stimulates the PI3K/Akt and ERK/RSK signaling pathways. We further demonstrated that HOTAIR exerts its effects on cell proliferation, at least in part, through the regulation of two YBX1 downstream targets phosphoenolpyruvate carboxykinase 2 (PCK2) and platelet derived growth factor receptor β. Our findings revealed a novel mechanism, whereby an lncRNA is able to regulate cell proliferation via altering intracellular protein localization. Moreover, the imaging tools developed herein have excellent potential for future in vivo imaging of lncRNA–protein interaction.

Chemotherapy is one of the major strategies for cancer treatment. Several antineoplastic drugs including vinorelbine (VRB) are commonly intravenously infused and liable to cause serious phlebitis. The therapeutic drugs for preventing this complication are limited. In this study, the mechanism of baicalein (BCN) was investigated on VRB-induced phlebitis in vivo and vascular endothelial cell injury in vitro. Treatment with BCN obviously attenuated vascular endothelial cell loss, edema, inflammatory cell infiltration and blood clots, and reduced the serum levels of TNF-α, IL-1β, IL-6 and ICAM-1 in the rabbit model of phlebitis induced by intravenous injection of VRB compared with vehicle. Further tests in vitro demonstrated that BCN lessened VRB-induced endothelial cell apoptosis, decreased intracellular ROS levels, suppressed phosphorylation of p38 and eventually inhibited activation of NF-κB signaling pathway. And these effects could be reversed by p38 agonist P79350. These results suggested that BCN exerted the protective effects against VRB-induced endothelial disruption in the rabbit model of phlebitis via inhibition of intracellular ROS generation and inactivation of p38/NF-κB pathway, leading to the decreased production of pro-inflammatory cytokines. Thus, BCN could be used as a potential agent for the treatment of phlebitis.

Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) play vital roles in the tumorigenesis of esophageal squamous cell carcinoma (ESCC). Nevertheless, the mechanism and regulatory network associated with this process remain largely unknown. In this study, we performed a comprehensive analysis of the expression of mRNAs, lncRNAs, and circRNAs by RNA-seq. A total of 3265 mRNAs, 1084 lncRNAs, and 38 circRNAs were found to be differentially expressed. Among these, 269 mRNAs were found to encode transcription factors (TFs). Functional enrichment analysis indicated that the dysregulated TFs are associated with the Hedgehog, Jak-STAT, TGF-beta, and MAPK signaling pathways. Furthermore, we constructed co-expression networks to screen the core lncRNAs and circRNAs involved in the regulation of transcription factors in these four pathways. Finally, we constructed a competing endogenous RNA (ceRNA) network of ESCC based on the abovementioned pathways. Our findings provide important insight into the role of lncRNAs and circRNAs in ESCC; the differentially expressed lncRNAs and circRNAs may represent potential targets for ESCC diagnosis and therapy.

A small molecule fluorescent probe (probe 1) based on adenine-coumarin derivative was designed and synthesized in this paper. Probe 1 exhibited a significant fluorescence-enhancing response to nucleic acids at 495 nm (for DNA) and 487 nm (for RNA). The fluorescence enhancement of probe 1 for DNA and RNA was 5.68 and 9.73 times respectively, the fluorescence quantum yield was changed from 2.5% to 11.7% and 22.5% accordingly. Meanwhile, an excellent linear relationship of fluorescence intensity at 495 nm or 487 nm versus the nucleic acid concentration (1 μM for probe 1, 0–350 μg/mL for DNA and 0–300 μg/mL for RNA) was obtained. Co-staining and nucleic acid digestion experiments showed that probe 1 could selectively image nucleic acids in mitochondria and nucleoli in HeLa cells.

Background FRAIL-NH has been commonly used to assess frailty in nursing home residents and validated in many ethnic populations; however, it has not been validated in mainland China, where such an assessment tool is lacking. This study aimed to (1) assess the discriminatory performance of FRAIL-NH in two-class frailty (non-frail+ pre-frail vs. frail) and three-class frailty (non-frail vs. pre-frail vs. frail), based on the Frailty Index (FI), (2) determine the appropriate cutoff points for FRAIL-NH that distinguish two-class and three-class frailty, and (3) examine the agreement in classification between FRAIL-NH and FI. Methods A cross-sectional study of 302 residents aged 60 years or older from six nursing homes in Changsha was conducted. The FRAIL-NH scale and 34-item FI were used to measure frailty. Two-way and three-way receiver operating characteristic (ROC) curves were used to estimate the performance of FRAIL-NH. Cohen’s Kappa statistics were used to examine the agreement between these two measures. Results The agreement between FRAIL-NH and FI ranged from 0.33 to 0.55. Regardless of what FI cutoff points were based on, the volume under the ROC surface (VUS) for FRAIL-NH from the three-way ROC were higher than the VUS of a useless test (1/6), and the area under the ROC curve (AUC) for FRAIL-NH from the two-way ROC were higher than the clinically meaningless value (0.5). When using FI cutoff points of 0.20 for pre-frail and 0.45 for frail, FRAIL-NH cutoff points of 1 and 9 in classifying three-class frailty had the highest VUS and the largest correct classification rates. Whichever FI was chosen, the performance of FRAIL-NH in distinguishing between pre-frailty and frailty, and between non-frailty and pre-frailty was equivalent. According to FRAIL-NH, the proportion of individuals with frailty misclassified as pre-frailty was higher than that of individuals with non-frailty misclassified as pre-frailty. Conclusion FRAIL-NH can be used as a preliminary frailty screening tool in nursing homes in mainland China. FI should be further used especially for those classified as pre-frailty by FRAIL-NH. It is not advisable to simply combine adjacent two classes of FRAIL-NH to create a new frailty variable in research settings.

Three 5H-benzo[a]phenoxazin-5-one-based (benzoresorufin and nile-red) Cysteine (Cys) detection probes have been comparatively designed and synthesized in this paper. The optical experiments exhibit probe 1b with a crotonoyl group has no response toward Cys; while probes 1a and 1c have the same reaction site (acryloyl group), their optical responses to Cys are quite different. The benzoresorufin-based-probe 1a shows a turn-on fluorescence response (118-fold) to Cys at 631 nm and affords a very low detection limit (DL = 19.8 nM). Compared with probe 1a, the nile-red-based probe 1c displays gradually diminishing fluorescence intensity with increased Cys concentration at 665 nm. And the notable different fluorescence response mechanisms of probes 1a and 1c toward Cys can be interpreted by HRMS and time-dependent density functional theorety (TDDFT) calculations. Furthermore, both of the two probes indicate high sensitivity and selectivity toward Cys over other similar structured amino acids including homocysteine (Hcy) and glutathione (GSH). Further cellular applications of the two probes have been successfully performed in HeLa cells.

Acquisition of features of mesenchymal cells represents a key step of metastatic progression of cancer cells and searching for mechanisms underlying the acquisition will help design novel clinical strategies for suppressing the metastatic progression. The Deleted in Liver Cancer-1 (DLC-1) gene is a p122/RhoGAP tumor/metastatic suppressor gene. However, the mechanism underlying DLC-1's inhibition of metastasis still remains largely unknown. In this study, we revealed that the DLC-1-deficient, but not the DLC-1-competent, human non-small cell lung carcinoma cells (NSCLCs) could acquire the TGF-β1-induced expression of CD105, a common surface marker of mesenchymal stem cells, with consequent increase in CD105-associated cell motility. Interestingly, the induced CD105 expression and cell motility were subjected to the inhibition by the DLC-1-RhoA-Rock1 signaling through inhibiting the serine phosphorylation at a linker region, but not at the C-terminus, of the Smad3 protein and Smad3 protein nuclear translocation down the canonical TGF-β1 signaling. In addition, the evidence suggested that DLC-1 very likely exerted its inhibitory effects on the TGF-β1 signaling and the associated CD105 acquisition in both the cytoplasm and the nucleus. Consistent to the in vitro findings, a reverse correlation between CD105 and DLC-1 in protein expression was identified in primary NSCLC tissues and their surrounding non-tumor tissues. In summary, this study revealed a novel anti-metastasis mechanism governed by the DLC-1 tumor/metastasis suppressor, thus helping design new diagnostic and therapeutic approaches for NSCLCs.

Translationally controlled tumor protein (TCTP) is a highly conserved housekeeping protein present in eukaryotic organisms. It is involved in regulating many fundamental processes and plays a critical role in tumor reversion and tumorigenesis. Increasing evidence suggests that TCTP plays a role in the regulation of cell fate determination and is a promising therapeutic target for cancer. To decipher the exact mechanisms by which TCTP functions and how all these functions are integrated, we analyzed the interactome of TCTP in HeLa cells by coimmunoprecipitation (IP) and mass spectrometry (MS). A total of 98 proteins were identified. We confirmed the in vitro and in vivo association of TCTP with six of the identified binding proteins using reciprocal IP and bimolecular fluorescence complementation (BiFC) analysis, respectively. Moreover, TCTP interacted with Y-box-binding protein 1 (YBX1), and their interaction was localized to the N-terminal region of TCTP and the 1-129 amino acid (aa) residues of YBX1. The YBX1 protein plays an important role in cell proliferation, RNA splicing, DNA repair, drug resistance, and stress response to extracellular signals. These data suggest that the interaction of TCTP with YBX1 might cooperate or coordinate their functions in the control of diverse regulatory pathways in cancer cells. Taken together, our results not only reveal a large number of TCTP-associated proteins that possess pleiotropic functions, but also provide novel insights into the molecular mechanisms of TCTP in tumorigenesis.

In this paper, the design of a lysosome-targetable pH probe that has a fluorescent OFF (pH = 4) to ON (pH = 5–6) response is described to identify lysosomes in normal cells. The mechanism of photoinduced electron transfer with a fluorophore-based reaction (FBR-PET) was proposed. Benzo[a]phenoxazines with electro-donating aryl groups were selected, its (2,5-dimethoxyphenyl)imino-, (2-hydroxyphenyl)imino- and (2-hydroxy-5-methoxyphenyl)- imino-derivatives (probes 1a−c) were prepared and their optical responses towards pH were evaluated; their fluorescence pH titration experiments gave regularly changes with the increasing electro-donating abilities at the linked aryl groups, the (2-hydroxy-5-methoxyphenyl)iminobenzo[a]phenoxazine (probe 1c) exhibited a nearly OFF−ON response at 580–800 nm. All probes were reversible, and they showed excellent selectivity toward the proton over other competitive species. Fluorescence confocal images were performed with HeLa, KB cancer cells and V79 normal cells, probes 1a−c are all lysosome-targetable pH probes, and benzo[a]phenoxazine with (2-hydroxy-5-methoxyphenyl)imino-group (probe 1c) has potential applications in selective differentiation of normal cells from cancer cells.

In this study, a mitochondria-specific fluorescent probe for efficient ratiometric detection of Cys was designed and investigated. Probe 1 is composed of a xanthylene skeleton and a benzyl group containing an acryloyl moiety. The probe showed excellent water solubility, good selectivity and sensitivity toward Cys over other analytes, and afforded an extremely low detection limit of 33.7 nM. The possible detection mechanism was ascertained by HRMS analysis. Moreover, probe 1 had excellent mitochondrial-targeting ability (the Pearson's correlation coefficient was 0.96), and was capable of monitoring endogenous Cys in living HeLa cells by dual channel ratiometric bioimaging, demonstrating its significant potential in biological applications.

Objective To investigate the diagnostic value of elasticity contrast index(ECI)in the differential diagnosis between benign and malignant cervical lymph nodes.Methods Cervical lymph nodes of 48 patients were examined by traditional ultrasound and ECI in Peking University Third Hospital between December 2016 and April 2017. Patients were further divided into free-hand group and non-free-hand group according to the use of manual compression or not. With pathological or clinical follow-up results as the gold standard,we compared the diagnostic values of traditional ultrasound,ECI,and their combination in the differential diagnosis between benign and malignant lymph nodes.Results Totally 138 lymph nodes were collected from 46 patients,among which 76 were benign and 62 were malignant. The ECI value of malignant lymph nodes(1.69±0.89)were significantly higher than that of benign lymph nodes(1.32±0.87)(t=-2.46,P=0.015).The area under receiver operating characteristic(ROC)curve for traditional ultrasound in discrimination of malignant cervical lymph nodes with benign ones was 0.899,with an optimal cut-off value of 7,which had a sensitivity of 93.5% and a specificity of 84.2%. The area under ROC curve for ECI was 0.649,with an optimal cut-off value of 1.25,which had a sensitivity of 59.7% and a specificity of 60.5%. For their combination,the area under ROC curve was 0.724,with a sensitivity of 93.5% and a specificity of 51.3%. In the group without using free-hand technique,the mean ECI value was 1.77±0.94 for malignant nodes,which was significantly higher than that(1.26±0.81)for benign nodes(t=-3.09,P=0.003). In the group requiring free-hand technique,the ECI value for malignant nodes was 1.33(1.01,1.44),showing no significant difference with benign ones[1.32(0.78,2.18);z=-0.20,P=0.843].Conclusions Conventional ultrasound has higher diagnostic value than ECI and their combination in differentiating benign and malignant lymph nodes. The role of ECI in evaluating other organs requires further investigations.

Physical activity (PA) has declined in China due to urbanization in the past two decades. Evidence-based programs are good approaches to promote PA, but are limited in China. Adopting existing programs can be a viable option. Prior to that, readiness assessment is needed. This study aimed to assess community readiness levels for disseminating evidence-based PA programs to older adults in Changsha, China. In-person interviews were conducted with 33 participants of five districts in Changsha to assess the community readiness level in five dimensions: community knowledge of efforts, community climate, community knowledge about the issue, leadership and resources. Data was transcribed, reviewed and compared with an anchored rating scale to provide a stage of readiness score ranging from 1 (no awareness) to 9 (high level of community ownership). Participants included 14 community staff, 13 older adults, four community leaders and three health professionals. The top three barriers to disseminating PA programs were lack of appropriate locations, funding and instructors. The top three resources were availability of indoor space, chairs and loudspeakers. Community leadership was the highest-rated readiness dimension (3.3 out of 9) followed by community climate (3.2), community knowledge of efforts (3.1) and resources (2.8); knowledge about the issue scored the lowest (2.7). The overall community stage readiness score of Changsha was 3.0 out of 9. The stage of readiness for communities in Changsha, China is ‘vague awareness’. Developing strategies to improve community readiness levels may increase evidence-based PA program dissemination in Changsha, China.

Two quinolone–coumarin skeleton derivatives (1a, 1b) have been prepared by Friedlander synthesis with 2-aminoaryl ketone and 3-acetyl-7-diethylaminocoumarin. The dyes showed excellent photo stability. Their optical properties in five organic solvents have been measured, and the wavelength range of the maximum fluorescence emission peaks was from 469 nm to 509 nm. Besides, both of them exhibited high fluorescence quantum yields (0.79–0.96) in these organic solvents. The pH influenced optical properties tests indicated dyes 1a–b have strong fluorescence in sub acid (pH = 6.0) to alkaline environment (pH = 9.0). Their fluorescence quantum yields in neutral aqueous solution (pH = 7.0) were 0.82 (1a) and 0.78 (1b) respectively. In addition, dyes 1a–b exhibited stable fluorescence intensity in the presence of some metal cations and biomolecules in neutral solution (pH = 7.0). Subsequently, confocal microscopy imaging indicated that dyes 1a–b could be used as biomarkers for lipid droplets in living and fixed cells (I929 and HeLa cells).

This study is to examine the influence of familiarity on energy intake, eating behavior, and concentration of the plasma gut hormones in lean and overweight young male subjects.Twenty-eight lean and twenty-eight overweight participants were recruited. Their food consumption was documented and analyzed when they had a test meal while they were paired with friends or strangers at the same weight stature. Their eating behavior was recorded with cameras hidden in the carton, and postprandial plasma gut hormone concentration were measured.Compared with overweight strangers (OS), overweight friends (OF) had increased food consumption, prolonged and decreased number of chews per 10 g food. Compared with OS, postprandial plasma concentration of cholecystokinin-8 was significantly lower in OF group at 30, 60, and 90 min, whereas the concentration of glucagon-like peptide 1 was significantly lower at 60 and 90 min. Plasma ghrelin concentration was significantly higher in the OF group than that in the OS group at 90 and 120 min. No significant differences in gut hormone concentration were observed between lean strangers (LS) and lean friends (LF) groups at all time points.Familiarity plays an important role in increasing energy intake and in changing of postprandial gut hormone concentration in overweight individuals.

Background Many factors may lead to sperm DNA damage. However, it is little known that the correlations of sperm DNA damage with obesity-associated markers, and reproductive hormones and lipids levels in serum and seminal plasma. Methods In our prospective study, a total of 1 010 subfertile men, aged from 18 to 50 years old, were enrolled from August 2012 through June 2015. Their obesity-associated markers, semen parameters, sperm acrosomal enzyme activity, seminal plasma biochemical markers, and reproductive hormones and lipids levels in serum and seminal plasma were detected. Sperm DNA fragmentation index (DFI) was determined by sperm chromatin structure assay. The correlations between DFI and each of the above-mentioned variables were analyzed. Results Spearman correlation analysis showed that sperm DFI was positively related to age and abstinence time (P

Conventional strategy of anti-EpCAM capture and immunostaining of cytokeratins (CKs) to detect circulating tumor cells (CTCs) is limited by highly heterogeneous and dynamic expression or absence of EpCAM and/or CKs in CTCs. In this study, a novel integrated cellular and molecular approach of subtraction enrichment (SE) and immunostaining-FISH (iFISH) was successfully developed. Both large or small size CTCs and circulating tumor microemboli (CTM) in various biofluid samples including cerebrospinal fluid (CSF) of cancer patients and patient-derived-xenograft (PDX) mouse models were efficiently enriched and comprehensively identified and characterized by SE-iFISH. Non-hematopoietic CTCs with heteroploid chromosome 8 were detected in 87-92% of lung, esophageal and gastric cancer patients. Characterization of CTCs performed by CK18-iFISH showed that CK18, the dual epithelial marker and tumor biomarker, was strong positive in only 14% of lung and 24% of esophageal CTCs, respectively. Unlike conventional methodologies restricted only to the large and/or both EpCAM and CK positive CTCs, SE-iFISH enables efficient enrichment and performing in situ phenotypic and karyotypic identification and characterization of the highly heterogeneous CTC subtypes classified by both chromosome ploidy and the expression of various tumor biomarkers. Each CTC subtype may possess distinct clinical significance relative to tumor metastasis, relapse, therapeutic drug sensitivity or resistance, etc.