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The complexities of energy transfer mechanisms in the flagella of mammalian sperm flagella have been intensively investigated and demonstrate significant diversity across species. Enzymatic shuttles, particularly adenylate kinase (AK) and creatine kinase (CK), are pivotal in the efficient transfer of intracellular ATP, showing distinct tissue- and species-specificity. Here, the expression profiles of AK and CK were investigated in mice and found to fall into four subgroups, of which Subgroup III AKs were observed to be unique to the male reproductive system and conserved across chordates. Both AK8 and AK9 were found to be indispensable to male reproduction after analysis of an infertile male cohort. Knockout mouse models showed that AK8 and AK9 were central to promoting sperm motility. Immunoprecipitation combined with mass spectrometry revealed that AK8 and AK9 interact with the radial spoke (RS) of the axoneme. Examination of various human and mouse sperm samples with substructural damage, including the presence of multiple RS subunits, showed that the head of radial spoke 3 acts as an adapter for AK9 in the flagellar axoneme. Using an ATP probe together with metabolomic analysis, it was found that AK8 and AK9 cooperatively regulated ATP transfer in the axoneme, and were concentrated at sites associated with energy consumption in the flagellum. These findings indicate a novel function for RS beyond its structural role, namely, the regulation of ATP transfer. In conclusion, the results expand the functional spectrum of AK proteins and suggest a fresh model regarding ATP transfer within mammalian flagella., (© 2024. Science China Press.)

Inner dynein arms (IDAs) are formed from a protein complex that is essential for appropriate flagellar bending and beating. IDA defects have previously been linked to the incidence of asthenozoospermia (AZS) and male infertility. The testes-enriched ZMYND12 protein is homologous with an IDA component identified in Chlamydomonas. ZMYND12 deficiency has previously been tied to infertility in males, yet the underlying mechanism remains uncertain. Here, a CRISPR/Cas9 approach was employed to generate Zmynd12 knockout (Zmynd12 -/- ) mice. These Zmynd12 -/- mice exhibited significant male subfertility, reduced sperm motile velocity, and impaired capacitation. Through a combination of co-immunoprecipitation and mass spectrometry, ZMYND12 was found to interact with TTC29 and PRKACA. Decreases in the levels of PRKACA were evident in the sperm of these Zmynd12 -/- mice, suggesting that this change may account for the observed drop in male fertility. Moreover, in a cohort of patients with AZS, one patient carrying a ZMYND12 variant was identified, expanding the known AZS-related variant spectrum. Together, these findings demonstrate that ZMYND12 is essential for flagellar beating, capacitation, and male fertility., (© 2024. The Author(s).)

Removing texture while preserving the main structure of an image is a challenging task. To address this, this paper propose an image smoothing method based on global gradient sparsity and local relative gradient constraints optimization. To reduce the interference of complex texture details, adopting a multi-directional difference constrained global gradient sparsity decomposition method, which provides a guidance image with weaker texture detail gradients. Meanwhile, using the luminance channel as a reference, edge-aware operator is constructed based on local gradient constraints. This operator weakens the gradients of repetitive and similar texture details, enabling it to obtain more accurate structural information for guiding global optimization of the image. By projecting multi-directional differences onto the horizontal and vertical directions, a mapping from multi-directional differences to bi-directional gradients is achieved. Additionally, to ensure the consistency of measurement results, a multi-directional gradient normalization method is designed. Through experiments, we demonstrate that our method exhibits significant advantages in preserving image edges compared to current advanced smoothing methods., (© 2024. The Author(s).)

Hepatocellular carcinoma (HCC) remains a formidable malignancy that significantly impacts human health, and the early diagnosis of HCC holds paramount importance. Therefore, it is imperative to develop an efficacious signature for the early diagnosis of HCC. In this study, we aimed to develop early HCC predictors (eHCC-pred) using machine learning-based methods and compare their performance with existing methods. The enhancements and advancements of eHCC-pred encompassed the following: (i) utilization of a substantial number of samples, including an increased representation of cirrhosis tissues without HCC (CwoHCC) samples for model training and augmented numbers of HCC and CwoHCC samples for model validation; (ii) incorporation of two feature selection methods, namely minimum redundancy maximum relevance and maximum relevance maximum distance, along with the inclusion of eight machine learning-based methods; (iii) improvement in the accuracy of early HCC identification, elevating it from 78.15 to 97% using identical independent datasets; and (iv) establishment of a user-friendly web server. The eHCC-pred is freely accessible at http://www.dulab.com.cn/eHCC-pred/ . Our approach, eHCC-pred, is anticipated to be robustly employed at the individual level for facilitating early HCC diagnosis in clinical practice, surpassing currently available state-of-the-art techniques., (© 2024. The Author(s).)

Hepatocellular carcinoma (HCC) is a highly detrimental cancer type and has limited therapeutic options, posing significant threats to human health. The development of HCC has been associated with a disorder in bile acid (BA) metabolism. In this study, we employed an integrative approach, combining various datasets and omics analyses, to comprehensively characterize the tumor microenvironment in HCC based on genes related to BA metabolism. Our analysis resulted in the classification of HCC samples into four subtypes (C1, C2a, C2b, and C3). Notably, subtype C2a, characterized by the highest bile acid metabolism score (BAMS), exhibited the highest survival probability. This subtype also demonstrated increased immune cell infiltration, lower cell cycle scores, reduced AFP levels, and a lower risk of metastasis compared to subtypes C1 and C3. Subtype C1 displayed poorer survival probability and elevated cell cycle scores. Importantly, the identified subtypes based on BAMS showed potential relevance to the gene expression of drug targets in currently approved drugs and those under clinical research. Genes encoding VEGFR (FLT4 and KDR) and MET were elevated in C2, while genes such as TGFBR1 , TGFB1 , ADORA3 , SRC , BRAF , RET , FLT3 , KIT , PDGFRA , and PDGFRB were elevated in C1. Additionally, FGFR2 and FGFR3 , along with immune target genes including PDCD1 and CTLA4 , were higher in C3. This suggests that subtypes C1, C2, and C3 might represent distinct potential candidates for TGFB1 inhibitors, VEGFR inhibitors, and immune checkpoint blockade treatments, respectively. Significantly, both bulk and single-cell transcriptome analyses unveiled a negative correlation between BA metabolism and cell cycle-related pathways. In vitro experiments further confirmed that the treatment of HCC cell lines with BA receptor agonist ursodeoxycholic acid led to the downregulation of the expression of cell cycle-related genes. Our findings suggest a plausible involvement of BA metabolism in liver carcinogenesis, potentially mediated through the regulation of tumor cell cycles and the immune microenvironment. This preliminary understanding lays the groundwork for future investigations to validate and elucidate the specific mechanisms underlying this potential association. Furthermore, this study provides a novel foundation for future precise molecular typing and the design of systemic clinical trials for HCC therapy.

Unsupervised domain adaption (UDA), which aims to enhance the segmentation performance of deep models on unlabeled data, has recently drawn much attention. In this paper, we propose a novel UDA method (namely DLaST) for medical image segmentation via disentanglement learning and self-training. Disentanglement learning factorizes an image into domain-invariant anatomy and domain-specific modality components. To make the best of disentanglement learning, we propose a novel shape constraint to boost the adaptation performance. The self-training strategy further adaptively improves the segmentation performance of the model for the target domain through adversarial learning and pseudo label, which implicitly facilitates feature alignment in the anatomy space. Experimental results demonstrate that the proposed method outperforms the state-of-the-art UDA methods for medical image segmentation on three public datasets, i.e., a cardiac dataset, an abdominal dataset and a brain dataset. The code will be released soon.

The secondary metabolites of indigenous plants have significant allelopathic inhibitory effects on the growth and development of invasive alien plants. Methyl palmitate (MP) and methyl linolenate (ML) were used as exogenous allelopathic substances. The research investigated the differences of inhibitory effects of MP and ML on the growth of seedlings of Alternanthera philoxeroides, and calculated their morphological characteristics, biomass, physiological indicators and the response index (RI). The synthetical allelopathic index (SE) of 1 mmol/L MP was the smallest (- 0.26) and the allelopathic inhibition was the strongest; therefore, it was selected as a 13 C-labeled allelochemical. The distribution of 1 mmol/L MP in different parts of A. philoxeroides and the correlation between the biomass ratios of roots, stems and leaves and the 13 C content were studied by 13 C stable isotope tracing experiments. Atom percent excess (APE) between roots, stems and leaves of A. philoxeroides treated with 1 mmol/L MP were significantly different in terms of magnitude, with leaves (0.17%) > roots (0.12%) > stems (0.07%). The root, stem and leaf biomass ratios of invasive weeds had great significant positive correlation with 13 C content (p < 0.01, R 2 between 0.96 and 0.99). This current research provides a new idea and method for the control of A. philoxeroides, but large-scale popularization remains to be studied., (© 2023. Springer Nature Limited.)

The emerging number of single-cell RNA-seq (scRNA-Seq) datasets allows the characterization of cell types across various cancer types. However, there is still lack of effective tools to integrate the various analysis of single-cells, especially for making fine annotation on subtype cells within the tumor microenvironment (TME). We developed scWizard, a point-and-click tool packaging automated process including our developed cell annotation method based on deep neural network learning and 11 downstream analyses methods. scWizard used 113,976 cells across 13 cancer types as a built-in reference dataset for training the hierarchical model enabling to automatedly classify and annotate 7 major cell types and 47 cell subtypes in the TME. scWizard provides a built-in pre-training set for user's flexible choice, and gives a higher accuracy for annotation subtypes of tumor-derived T -lymphocytes/natural killer cells (T/NK) and myeloid cells from different cancer types compared with the existing five methods. scWizard has good robustness in three independent cancer datasets, with an accuracy of 0.98 in annotating major cell types, 0.85 in annotating myeloid cell subtypes and 0.79 in annotating T/NK cell subtypes, indicting the wide applicability of scWizard in different cell types of cancers. Finally, the automatic analysis and visualization function of scWizard are presented by using the intrahepatic cholangiocarcinoma (ICC) scRNA-Seq dataset as a case. scWizard focuses on decoding TME and covers various analysis flows for cancer scRNA-Seq study, and provides an easy-to-use tool and a user-friendly interface for researchers widely, to further accelerate the biological discovery of cancer research., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Ubiquitination is an important posttranslation modification (PTM) that regulates a variety of cellular processes, including protein degradation, DNA repair, and viral infections. In this process, the C-terminal carboxyl group of ubiquitin (Ub) or poly-Ub is attached to the ε-amine of lysine (Lys) side chain of an acceptor protein through an isopeptide bond. Studying a molecular mechanism of ubiquitination and deubiquitination is fundamental for unraveling its precise role in health and disease and hence crucial for drug development. Enzymatic approaches for protein ubiquitination possess limited ability to selectivity install Ub or Ub chain on the desired position of an acceptor protein and often lead to heterogeneous mixtures. In the past decades, chemical protein (semi)synthesis has been proved to be an efficient tool to facilitate site-specific protein ubiquitination, which significantly contributes to decode the Ub signal at molecular and structural levels. In this review, we summarize the synthetic strategies developed for protein ubiquitination, and the achievements to generate monoubiquitinated, di-ubiquitinated, and tetraubiquitinated proteins with native isopeptide and ester bonds., (© 2021 European Peptide Society and John Wiley & Sons, Ltd.)

Background: A method for predicting prognosis of patients who undergo partial hepatectomy for huge hepatocellular carcinoma (HHCC, diameter ≥10 cm) is currently lacking. This study aimed to establish two online nomograms to predict the overall survival (OS) and disease-free survival (DFS) for patients undergoing resection for HHCC., Methods: The clinicopathologic characteristics and follow-up information of patients who underwent partial hepatectomy for HHCC at two medical centers were reviewed. Using a training cohort, a Cox model was used to identify the predictors of survival. Two dynamic nomograms for OS and DFS were developed and validated based on the data., Results: Eight and nine independent factors derived from the multivariate analysis of the training cohort were screened and incorporated into the nomograms for OS and DFS, respectively. In the training cohort, the nomogram achieved concordance indices (C-indices) of 0.745 and 0.738 in predicting the OS and DFS, respectively. These results were supported by external validation (C-indices: 0.822 for OS and 0.827 for DFS). Further, the calibration curves of the endpoints showed a favorable agreement between the nomograms' assessments and actual observations., Conclusions: The two web-based nomograms demonstrated optimal predictive performance for patients undergoing partial hepatectomy for HHCC. This provides a practical method for a personalized prognosis based on an individual's underlying risk factors., (Copyright © 2020 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

The sliding-window-based dynamic functional connectivity network (D-FCN) has been becoming an increasingly useful tool for understanding the changes of brain connectivity patterns and the association of neurological diseases with these dynamic variations. However, conventional D-FCN is essentially low-order network, which only reflects the pairwise interaction pattern between brain regions and thus overlooking the high-order interactions among multiple brain regions. In addition, D-FCN is innate with temporal sensitivity issue, i.e., D-FCN is sensitive to the chronological order of its subnetworks. To deal with the above issues, we propose a novel high-order functional connectivity network framework based on the central moment feature of D-FCN. Specifically, we firstly adopt a central moment approach to extract multiple central moment feature matrices from D-FCN. Furthermore, we regard the matrices as the profiles to build multiple high-order functional connectivity networks which further capture the higher level and more complex interaction relationships among multiple brain regions. Finally, we use the voting strategy to combine the high-order networks with D-FCN for autism spectrum disorder diagnosis. Experimental results show that the combination of multiple functional connectivity networks achieves accuracy of 88.06%, and the best single network achieves accuracy of 79.5%., Competing Interests: Dinggang Shen is an employee of Shanghai United Imaging Intelligence Co., Ltd. The authors declare that they have no competing interests., (© 2021 Xie et al.)

Primary brain tumors are a rare occurrence in comparison to other malignancies, the most predominant form being glioma. Commonly, exposure to ionizing radiations and inheritance of associated conditions such a neurofibromatosis and tuberous sclerosis are the most common causes of development of glioma. However, understanding of the molecular mechanisms that drive glioma development is limited. We explore the role of aberration of microRNA namely miR-494-3p through long noncoding RNA WT1-AS in the development of gliomas. In this study, we found that, levels of WT1-AS were significantly reduced in glioma tissues and cell lines. The miR-494-3p levels were negatively correlated with WT1-AS levels. The cellular proliferation and invasiveness decreased in WT1-AS transfected cell lines. Further the half maximal inhibitory concentration (IC 50 ) of chemotherapeutic agent temozolomide was significantly reduced in the presence of WT1-AS . The cotransfection of WT1-AS and miR-494-3p reduced activation of phospho-AKT (p-AKT). Expression of miR-494-3p is modulated by binding to long noncoding RNA WT1-AS . Deregulation of WT1-AS leads to aberrant expression of miR-494-3p leading to hyperactivation of AKT. This malformation may result in altering protective immune responses in malignancies. Targeting of WT1-AS, miR-494-3p, and AKT may be novel therapeutic options in treatment of glioma.

This paper presents a ballistocardiogram (BCG) based beat-to-beat heart rate (HR) measurement system for healthcare applications in smart home. The BCG signal is picked up by two parallel connected piezoelectric elements, and processed by a robust HR detection algorithm. To deal with the diversity in BCG signal, a personalized heartbeat template is extracted to handle the diversity in BCG signal. The Pearson correlation coefficient is used to correlate between personalized template and the BCG signal. Heartbeats are detected by using the Hilbert Transform. The system is verified on 32 subjects with simultaneously recorded BCG and ECG signals. With the reference to ECG signal, we have achieved mean absolute relative error of the beat-to-beat intervals of 4.56%, and average absolute error ±standard deviation of absolute error for HR estimation in a 30-seconds window of 0.59 ±0.56 beats per minute. Meanwhile, 99.67% of the beat-to-beat intervals are detected on average.

The Sonic hedgehog (Shh) signaling pathway may be interrelated with other signaling pathways, such as the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways in gastrointestinal stromal tumor (GIST). The present study investigated the interaction among Shh, PI3K and MAPK signaling pathways in GIST cells. The expression of PI3K, MAPK and Shh signaling pathways in GIST-H1 cells were upregulated by endothelial growth factor (EGF) and recombinant Shh (N-shh) stimulation, and were downregulated by specific inhibitors of each signaling pathway. The proliferation rate of GIST-H1 cells were significantly increased under EGF or N-shh treatment (P<0.01). In addition, this effect was partially prevented by the pretreatment of the inhibitors of these signaling pathways. In summary, a cross regulation exists among the Shh, PI3K and MAPK signaling pathways in GIST-H-1 cells. The combined use of the inhibitors of these signaling pathways is a potentially novel option for GIST targeted therapy.

This study presents a robust heart rate monitoring algorithm using photoplethysmography (PPG) signal during physical exercise. The proposed method combines two stage: motion artifact removal and frequency refinement. The cascaded normalized least mean square adaptive filter is used to attenuate the noise introduced by motion artifacts in the PPG signal. A phase vocoder technique is used to refine the frequency calculated by Fourier Transform, from which the heart rate is finally tracked. On a publicly available database of twelve PPG recordings, the proposed technique obtains an average absolute error (AAE) of 1.08 beat per minute (BPM). Person correlation coefficient of 0.997 is achieved between true heart rate and estimated heart rate. In contrast to other available approaches, the proposed method has merely one parameter to tune in spectral peak tracking step for heart rate estimation.

This study proposes a new method for motion artifact (MA) removal in Photoplethysmography (PPG) signal that combines accurate heart rate (HR) frequency estimation and notch filtering. The method applies LMS-Newton adaptive filtering to reduce motion artifact noise and uses a novel HR correction stage for accurate HR frequency estimation. Notch filters are used to recover clean PPG signal from HR frequency and second harmonic frequency of PPG. On a widely used dataset of 12 recordings, our method achieves an averaged HR error of 0. 92bpm and a Pearson correlation of 0.997. Experimental results further show that our method can recover the PPG waveform with clear dicrotic peaks even for strongly MA-corrupted PPG signal.

Background: Minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) has been employed in increasing cases compared with open TLIF (Open-TLIF). However, it is uncertain whether the advantages of MI-TLIF can also be specifically applied in obese patients. Therefore, the current study was thereby carried out aiming to compare the outcomes of MI-TLIF with those of Open-TLIF in obese patients with lumbar degenerative diseases., Methods: Electronic databases were systemically retrieved from construction to May 2017. Meanwhile, the odds ratio (OR), mean difference (MD) and 95% confidence intervals (CI) were determined., Results: A total of 7 observational cohort studies were enrolled into the current meta-analysis. The results indicated that, compared with Open-TLIF group, MI-TLIF could remarkably reduce the operative time (P = 0.002), intraoperative blood loss (P < 0.001), postoperative drainage (P = 0.01), length of stay (P < 0.001) and incidence of complications (P < 0.001). In addition, MI-TLIF could also lead to markedly lower early back pain-Visual Analog Scale (BP-VAS) score than that of Open-TLIF (P < 0.001), but no statistically significant differences were found in Oswestry Disability Index (ODI), late BP-VAS, early leg pain-VAS (LP-VAS) and late LP-VAS scores., Conclusion: MI-TLIF may be a more preferred choice for obese patients undergoing spinal surgery. However, differences in the long-term functional and pain outcomes between MI-TLIF and Open-TLIF remain a source of controversy, which should be further verified in future randomized-control trials.

Objective: β-Blocker exposure has been shown to reduce mortality in traumatic brain injury (TBI); however, the efficacy of β-blockers remains inconclusive. Therefore, a meta-analysis was conducted in this paper to evaluate the safety and efficacy of β-blocker therapy on patients with TBI., Methods: The electronic databases were systemically retrieved from construction to February 2017. The odds ratio (OR), mean difference (MD) and 95% confidence intervals (CI) were determined., Results: A total of 13 observational cohort studies involving 15,734 cases were enrolled. The results indicated that β-blocker therapy had remarkably reduced the in-hospital mortality (OR 0.33; 95% CI 0.27-0.40; p<0.001). However, β-blocker therapy was also associated with increased infection rate (OR 2.01; 95% CI 1.50-2.69; p<0.001), longer length of stay (MD=7.40; 95% CI=4.39, 10.41; p<0.001) and ICU stay (MD=3.52; 95% CI=1.56, 5.47; p<0.001). In addition, β-blocker therapy also led to longer period of ventilator support (MD=2.70; 95% CI=1.81, 3.59; p<0.001)., Conclusion: The meta-analysis demonstrates that β-blockers are effective in lowering mortality in patients with TBI. However, β-blocker therapy has markedly increased the infection rate and requires a longer period of ventilator support, intensive care management as well as length of stay., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The present study investigated the effect of combined sorafenib chemotherapy on hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression and survival time of patients with advanced gastric cancer. From January 2010 to December 2011, 92 patients diagnosed with advanced gastric cancer were selected and randomly divided into the treatment group and control group. The treatment group was treated with sorafenib chemotherapy combined with 5-fluorouracil (5-FU), and the control group received 5-FU. The treatment course was 3-4 cycles. During the same period, 46 healthy persons admitted to the Second People's Hospital of Huaian were selected as the controls. A volume of 3-4 ml peripheral blood from each patient and control was collected before and after treatment. The expression levels of HIF-1α and VEGF in peripheral blood were measured by ELISA. The survival time of patients with advanced gastric cancer was followed and analyzed. Compared with healthy controls, serum levels of HIF-1α and VEGF were significantly higher in patients with advanced gastric cancer (P<0.05). After chemotherapy combined with sorafenib, the peripheral blood levels of HIF-1α and VEGF decreased significantly in the treatment group (P<0.05). The 5-year survival rate of patients in the two groups was followed. Compared with the control group, the 1-year survival rate of the treatment group was significantly higher (P<0.05). In conclusion, chemotherapy combined with sorafenib can effectively reduce serum levels of HIF-1α and VEGF in patients with advanced gastric cancer, and improve their 1-year survival rate and prognosis. Therefore, it has significant clinical application value.

Background/aims: Glycine is a strychnine-sensitive inhibitory neurotransmitter in the central nervous system (CNS), especially in the spinal cord, brainstem, and retina. The objective of the present study was to investigate the potential neuroprotective effects of GlyT1 inhibitor N [3-(4'-fluorophenyl)-3-(4'-phenylphenoxy) propyl] sarcosine (NFPS) in the rat model of experimental stroke., Methods: In vivo ischaemia was induced by transient middle cerebral artery occlusion (tMCAO). The methods of Western Blotting, Nissl Staining and Morris water maze methods were applied to analyze the anti-ischaemia mechanism., Results: The results showed that high dose of NFPS (H-NFPS) significantly reduced infarct volume, neuronal injury and the expression of cleaved caspase-3, enhanced Bcl-2/Bax, and improved spatial learning deficits which were administered three hours after transient middle cerebral artery occlusion (tMCAO) induction in rats, while, low dose of NFPS (L-NFPS) exacerbated the injury of ischaemia. These findings suggested that low and high dose of NFPS produced opposite effects. Importantly, it was demonstrated that H-NFPS-dependent neuronal protection was inverted by salicylate (Sal), a specific GlyR x0251;1 antagonist. Such effects could probably be attributed to the enhanced glycine level in both synaptic and extrasynaptic clefts and the subsequently altered extrasynaptic GlyRs and their subtypes., Conclusions: These data imply that GlyT1 inhibitor NFPS may be a novel target for clinical treatment of transient focal cerebral ischaemia and reperfusion which are associated with altered GlyR alpha 1 subunits., (© 2016 S. Karger AG, Basel.)

B cell CLL/lymphoma 6 member B (BCL6B) is expressed in many normal tissues but expressed at very low levels in cancer tissues. It was reported that BCL6B inhibits hepatocellular carcinoma (HCC) metastases, but the exact role of BCL6B in HCC remains to be investigated. BCL6B expression was significantly decreased in HCC tissues compared with paired non-cancer tissues. Low BCL6B expression in tumors was correlated with shorter overall survival in patients, and multivariate Cox regression analysis revealed that BCL6B expression was an independent prognostic factor for human HCC patients. Moreover, a positive correlation between BCL6B expression and hepatic cirrhosis was found in an analysis of HCC clinicopathological characteristics. BCL6B expression was increased in rat fibrotic liver samples in response to liver injury. BCL6B transgenic rats were less susceptible to hepatocellular damage, inflammation and fibrosis. In vitro studies demonstrated that BCL6B inhibited the activation of hepatic stellate cells though upregulation of hepatocyte growth factor. In addition, transcriptomic microarray analysis was performed to explore the mechanisms in which BCL6B confers protection from tumorigenesis. In conclusion, BCL6B plays a pivotal role as a prognostic biomarker for HCC, and the restoration of BCL6B may be a novel strategy as an anti-fibrogenic therapy for human HCC.

In previous studies, we confirmed that mitofusin-2 (Mfn2) induced apoptosis in hepatocellular carcinoma (HCC) cells. However, the exact molecular mechanism remained unclear. Mfn2 expressed lower in tumour tissues, compared with adjacent non-cancer tissues. Furthermore, Mfn2 immunostaining was very weak in HCC tissue (P < 0.05) and was significantly associated with tumour size and TNM stage (P = 0.038 and 0.040, respectively), and patients with HCC with lower Mfn2 expression had a poorer prognosis. Overexpression of Mfn2 induced HepG2 cells apoptosis, reduced the mitochondrial membrane potential (ΔΨm) and endoplasmic reticulum (ER) calcium ion (Ca(2+)) concentrations, and elevated intracellular reactive oxygen species (ROS) and mitochondrial Ca(2+) concentrations. However, when HepG2 cells overexpressing Mfn2 were treated with both heparin and RU360, there was no induction of apoptosis, decline in ΔΨm or ER Ca(2+), or increase in intracellular ROS or mitochondrial Ca(2+). We also found downregulation in the expression of mitochondrial calcium uptake1 and 2 (MICU1 and MICU2) in cells transfected with Adv-Mfn2. Thus, we confirmed that Mfn2 induced apoptosis in HCC cells by triggering influx of Ca(2+) into the mitochondria from the ER., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Standard-volume polyethylene glycol (PEG) gut lavage solutions are safe and effective, but they require the consumption of large volumes of fluid. A new lower-volume solution of PEG plus ascorbic acid has been used recently as a preparation for colonoscopy., Aim: A meta-analysis was performed to compare the performance of low-volume PEG plus ascorbic acid with standard-volume PEG as bowel preparation for colonoscopy., Study: Electronic and manual searches were performed to identify randomized controlled trials (RCTs) that compared the performance of low-volume PEG plus ascorbic acid with standard-volume PEG as bowel preparation for colonoscopy. After a methodological quality assessment and data extraction, the pooled estimates of bowel preparation efficacy during bowel cleansing, compliance with preparation, willingness to repeat the same preparation, and the side effects were calculated. We calculated pooled estimates of odds ratios (OR) by fixed- and/or random-effects models. We also assessed heterogeneity among studies and the publication bias., Results: Eleven RCTs were identified for analysis. The pooled OR for preparation efficacy during bowel cleansing and for compliance with preparation for low-volume PEG plus ascorbic acid were 1.08 (95% CI = 0.98-1.28, P = 0.34) and 2.23 (95% CI = 1.67-2.98, P<0.00001), respectively, compared with those for standard-volume PEG. The side effects of vomiting and nausea for low-volume PEG plus ascorbic acid were reduced relative to standard-volume PEG. There was no significant publication bias, according to a funnel plot., Conclusions: Low-volume PEG plus ascorbic acid gut lavage achieved non-inferior efficacy for bowel cleansing, is more acceptable to patients, and has fewer side effects than standard-volume PEG as a bowel preparation method for colonoscopy.

Background: The enhanced liver fibrosis test (ELF) has been shown to accurately predict significant liver fibrosis in several liver diseases., Aims: To perform a meta-analysis to assess the performance of the ELF test for the assessment of liver fibrosis., Study: Electronic and manual searches were performed to identify studies of the ELF test. After methodological quality assessment and data extraction, pooled estimates of the sensitivity, specificity, area under the receiver operating characteristic curve (AUROC), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and summary receiver operating characteristics (sROC) were assessed systematically. The extent of heterogeneity and reasons for it were assessed., Results: Nine studies were identified for analysis. The pooled sensitivity, specificity, positive LR, negative LR, and DOR values of ELF test, for assessment of significant liver fibrosis, were 83% (95% CI=0.80-0.86), 73% (95% CI=0.69-0.77), 4.00 (95% CI=2.50-6.39), 0.24 (95% CI=0.17-0.34), and 16.10 (95% CI=8.27-31.34), respectively; and, for evaluation of severe liver fibrosis, were 78% (95% CI=0.74-0.81), 76% (95% CI=0.73-0.78), 4.39 (95% CI=2.76-6.97), 0.27 (95% CI=0.16-0.46), and 16.01 (95% CI: 7.15-35.82), respectively; and, for estimation of cirrhosis, were 80% (95% CI=0.75-0.85), 71% (95% CI=0.68-0.74), 3.13 (95% CI=2.01-4.87), 0.29 (95% CI=0.19-0.44), and 14.09 (95% CI: 5.43-36.59), respectively., Conclusions: The ELF test shows good performance and considerable diagnostic value for the prediction of histological fibrosis stage.

C-X-C motif chemokine ligand 14 (CXCL14) is a novel gene that is expressed in many normal cells but is absent from or expressed at very low levels in cancerous tissues such as head and neck squamous cell carcinoma (HNSCC), prostate cancer, and pancreatic cancer. However, the relationship between CXCL14 and hepatocellular carcinoma (HCC) remains unclear. Therefore, the exact function of CXCL14, which may modulate antitumor immune responses in certain cancers, was evaluated. CXCL14 was downregulated in HCC tissues compared to adjacent normal tissues. Moreover, overexpression of CXCL14 had an inhibitory effect on cell proliferation, induced apoptosis and inhibited the invasion of HCC cells in vitro. Upregulation of CXCL14 by lentivirus also significantly suppressed the growth of subcutaneous tumors in nude mice in vivo. We further demonstrated that the loss of CXCL14 expression was regulated by promoter hypermethylation. CXCL14 induced tumor cell apoptosis through both the mitochondrial and nuclear apoptosis pathways. CXCL14 suppressed tumor cell proliferation through regulation of the cell cycle by downregulation of cyclins and cyclin-dependent kinases. In conclusion, CXCL14 plays a pivotal role as a potential tumor suppressor in HCC. The re-expression or upregulation of this gene may provide a novel strategy in HCC therapy in the future., (© 2013 Japanese Cancer Association.)

Adipose-derived stem cells (ADSCs) exhibit tremendous potential for repair of ischemic diseases. However, studies on the fate, migration, differentiation, and body distribution of the labeled ADSCs are rarely reported. In this study, magnetic iron oxide nanoparticles were designed, synthesized, and coated with meso-2,3-dimercaptosuccinic acid (DMSA) to produce DMSA nanoparticles (DMSA-NPs). The properties, size distribution, and characterization of DMSA-NPs were evaluated. Green fluorescent protein expressing ADSCs (GFP-ADSCs) were obtained and labeled with DMSA-NPs. The viability, cytotoxicity and multi-differentiation capacity of labeled GFP-ADSCs were evaluated in vitro. Labeled and non-labeled GFP-ADSCs were injected into a mouse model of hindlimb ischemia, and 3T magnetic resonance imaging (MRI) was acquired. The synthesized DMSA-NPs efficiently labeled the GFP-ADSCs in vitro and in vivo without affecting cell viability, proliferation, cell cycle, and multi-differentiation capacity. The MRI showed hypointense spots in the labeled GFP-ADSCs that lasted up to 8 weeks. Prussian blue staining and immunofluorescence assay at 4 and 8 weeks indicated that the labeled GFP-ADSCs were in and around the ischemic sites and some differentiated into capillaries. This observation is identical to that seen for transplants of unlabeled cells. Labeled cells were also identified mainly in the liver and spleen, with significantly smaller amounts in the lungs, intestines, heart, and kidney. Developed DMSA-NPs were shown to exhibit a considerable potential for use as nanoprobes for MRI of stem cells, which will enhance our understanding of cell-based therapeutic strategies for ischemic diseases., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

CXC chemokine receptor 4 (CXCR4) is a cell surface molecule expressed in a distinct subset of glioma cells with enhanced tumorigenicity, and it is related to many important biological activities of the tumor. We supposed that this receptor might be a cell surface "marker" for glioma stem cells. This hypothesis was tested both in vitro and in vivo. The CXCR4+ and CXCR4- subsets were sorted from three human malignant glioma specimens. They were tested for the capability of colony formation in soft agar, generation of tumorosphere, self-renewal, and multipotent differentiation in vitro, and the capability of xenograft tumor in vivo. Drug and radiation resistance and coexpression with CD133 were studied for each subset. CXCR4+ glioma cells, but not CXCR4- cells, were capable of generating tumorospheres in serum-free medium. In addition, these spheres were able to self-renew after passage, and had multipotent differentiation after being induced in serum-containing medium. In soft agar assay, CXCR4+ cells generate much more colonies. The animal experiment revealed that CXCR4+ subpopulation had stronger tumorigenicity than the unsorted parental glioma cells, while the CXCR4- cells did not generate xenograft tumor. CXCR4-possitive cells were more resistant to temozolomide and radiation treatment. Both CXCR4+ and CXCR4- subsets contained very few CD133+ cells. The CXCR4+ subsets of glioma cells fulfill the standard of "cancer stem cell".