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Background: This study aimed to explore the electrocardiographic (ECG) characteristics of ventricular arrhythmia (VA) arising from epicardial and endocardial areas adjacent to mitral annual (MA). Methods: This study involved 283 patients with MA-VA who received radiofrequency catheter ablation at the center. The ECG characteristics of these patients were analyzed retrospectively. Results: The origin of MA-VA was judged based on the ECG variables. Among all MA-VAs, IDT > 77 ms or MDI > 0.505 predicted the VAs arising from epicardium (sensitivity of 70.20% and 73.51%, specificity of 94.70% and 82.58%, positive predictive value (PPV) of 93.81% and 82.84%, and negative predictive value (NPV) of 73.53% and 73.15%). Among all epicardial MA-VAs, the RV1/RV2 ratio > 0.87 predicted the VAs originating from the epicardial anteroseptal wall adjacent to MA. It had sensitivity, specificity, PPV, and NPV of 62.86%, 98.06%, 91.67%, and 88.60%, respectively. Among all endocardial MA-VAs, Q(q)R(r) morphology in lead V1 predicted the VAs arising from the endocardial septal wall adjacent to MA. It had sensitivity, specificity, PPV, and NPV of 92.98%, 100%, 100%, and 94.94%, respectively. Among all endocardial septal MA-VAs, a predominant positive wave in lead II and a predominant negative wave in lead III predicted the VAs arising from the endocardial mid-septal portion adjacent to MA. It had sensitivity, specificity, PPV, and NPV of 86.04%, 100%, 100%, and 70.00%, respectively. Conclusion: ECG characteristics of VAs from the different sites adjacent to MA can judge the arrhythmia’s origin and design the ablation plan accordingly.

Figure S2 shows that down-regulation of SAFB activated NF-κB signaling pathway

Supplementary Figure and Table Legends. List of supporting information

Purpose: To investigate the role and the underlying mechanism of scaffold attachment factor B (SAFB) in the progression of colorectal cancer (CRC).Experimental Design: SAFB expression was analyzed in the Cancer Outlier Profile Analysis of Oncomine and in 175 paraffin-embedded archived CRC tissues. Gene Ontology analyses were performed to explore the mechanism of SAFB in CRC progression. Western blot, RT-PCR, luciferase assay, and chromatin immunoprecipitation (ChIP) were used to detect the regulation of transforming growth factor-β–activated kinase 1 (TAK1) and NF-κB signaling by SAFB. The role of SAFB in invasion, metastasis, and angiogenesis was investigated using in vitro and in vivo assays. The relationship between SAFB and TAK1 was analyzed in CRC tissues.Results: SAFB was downregulated in CRC tissues, and low expression of SAFB was significantly associated with an aggressive phenotype and poorer survival of CRC patients. The downregulation of SAFB activated NF-κB signaling by targeting the TAK1 promoter. Ectopic expression of SAFB inhibited the development of aggressive features and metastasis of CRC cells both in vitro and in vivo. The overexpression of TAK1 could rescue the aggressive features in SAFB-overexpressed cells. Furthermore, the expression of SAFB in CRC tissues was negatively correlated with the expression of TAK1- and NF-κB–related genes.Conclusions: Our results show that SAFB regulated the activity of NF-κB signaling in CRC by targeting TAK1. This novel mechanism provides a comprehensive understanding of both SAFB and the NF-κB signaling pathway in the progression of CRC and indicates that the SAFB–TAK1–NF-κB axis is a potential target for early therapeutic intervention in CRC progression. Clin Cancer Res; 23(22); 7108–18. ©2017 AACR.

Supplementary Fig. S1-S9. Supplementary Fig. S1. miR-195 expression is significantly reduced in both human PCa cells and tissues; Supplementary Fig. S2. Kaplan-Meier analyses of biochemical recurrence (BCR)-free survival, non-metastatic BCR-free, survival overall survival and non-metastatic survival of prostate cancer (PCa) patients based on miR-195 expression in Taylor dataset; Supplementary Fig. S3. Knockdown of miR-195 expression enhances invasion, migration, but inhibits apoptosis of LNCaP and DU145 cells; Supplementary Fig. S4. The inhibition of miR-195 enhances tumor growth, angiogenesis and invasion in vivo; Supplementary Fig. S5. Top ten enriched KEGG pathways (A) and gene ontology (GO) biological processes (B) involved by differentially-expressed proteins induced by miR-195; Supplementary Fig. S6. The knockdown of RPS6KB1 could imitate the tumor suppressive effects of miR-195; Supplementary Fig. S7. The re-expression and knockdown of RPS6KB1 could respectively rescue and imitate the tumor suppressive effects of miR-195; Supplementary Fig. S8. Reverse correlation between miR-195 and RPS6KB1 expression in human PCa tissues; Supplementary Fig. S9. MMP-9, VEGF, BAD and E-cadherin function as downstream effectors of miR-195-RPS6KB1 axis.

Supplementary Tab S1-S9. Supplementary Tab. S1. Follow-up clinicopathological information of patients from MGH cohort; Supplementary Tab. S2. ligonucleotide Sequence for all the primers used in the study; Supplementary Tab.S3. The antibodies used in this study; Supplementary Tab.S4. Associations of miR-195 and RPS6KB1 protein expression with clinicopathological features of prostate cancer (PCa) patients; Supplementary Tab.S5. Prognostic value of miR-195 expression for the biochemical recurrence-free survival in univariate and multivariate analysis by Cox Regression; Supplementary Tab. S6 Differentially expressed proteins detected by iTRAQ; Supplementary Tab. S7 Canonical pathways analysis by IPA; Supplementary Tab. S8 Diseases and bio functions analysis by IPA; Supplementary Tab.S9. Prognostic value of RPS6KB1 expression for the biochemical recurrence-free survival in univariate and multivariate analysis by Cox Regression.

Supplementary materials, methods and tables

Purpose: To investigate the involvement of hsa-miRNA-195-5p (miR-195) in progression and prognosis of human prostate cancer.Experimental Design: qRT-PCR was performed to detect miR-195 expression in both prostate cancer cell lines and clinical tissue samples. Its clinical significance was statistically analyzed. The roles of miR-195 and its candidate target gene, ribosomal protein S6 kinase, 70 kDa, polypeptide 1 (RPS6KB1) in prostate cancer progression were confirmed on the basis of both in vitro and in vivo systems.Results: miR-195 downregulation in prostate cancer tissues was significantly associated with high Gleason score (P = 0.001), positive metastasis failure (P < 0.001), and biochemical recurrence (BCR, P < 0.001). Survival analysis identified miR-195 as an independent prognostic factor for BCR-free survival of prostate cancer patients (P = 0.022). Then, we confirmed the tumor suppressive role of miR-195 through prostate cancer cell invasion, migration, and apoptosis assays in vitro, along with tumor xenograft growth, angiogenesis, and invasion in vivo according to both gain-of-function and loss-of-function experiments. In addition, RPS6KB1 was identified as a novel direct target of miR-195 through proteomic expression profiling combined with bioinformatic target prediction and luciferase reporter assay. Moreover, the reexpression and knockdown of RPS6KB1 could respectively rescue and imitate the effects induced by miR-195. Importantly, RPS6KB1 expression was closely correlated with aggressive progression and poor prognosis in prostate cancer patients as opposed to miR-195. Furthermore, we identified MMP-9, VEGF, BAD, and E-cadherin as the downstream effectors of miR-195–RPS6KB1 axis.Conclusion: The newly identified miR-195–RPS6KB1 axis partially illustrates the molecular mechanism of prostate cancer progression and represents a novel potential therapeutic target for prostate cancer treatment. Clin Cancer Res; 21(21); 4922–34. ©2015 AACR.

Supplementary Methods

By cross-catenating two DNA rings containing palindromic fragments, we demonstrate a catenane-based grid-patterned periodic DNA monolayer array ([2]GDA) capable of accumulating in tumor tissues and amenable to the delivery of anticancer drugs.

Limosilactobacillus reuteri was encapsulated using Maillard-reaction-products (MRPs) of soy protein isolate (SPI) and α-lactose monohydrate by freeze-drying. The mixed solution of SPI and α-lactose monohydrate was placed in a water bath at 89°C for 160 min for Maillard reaction, and then freeze-dried to obtain MRPs. The effects of Maillard reaction on functional characteristics of MRPs and the properties of MRPs-microcapsules were studied. SDS-PAGE indicated that SPI subunit reacted with lactose to form a polymer, and the band of MRPs disappeared around the molecular weights of 33, 40, 63, and 100 kDa. Compared with SPI, the emulsion stability, emulsion activity, foaming capacity, foam stability, and gel strength of MRPs were increased by 259%, 55.71%, 82.32%, 58.53%, and 3266%, respectively. The results of Fourier transform infrared spectroscopy, circular dichroism spectroscopy, and scanning electron micrographs confirmed that the protein structure also changed significantly. Then, MRPs were used as wall material to prepare L. reuteri microcapsules. Physical properties and viable counts of L. reuteri during the simulated gastrointestinal digestion and storage period were determined. The particle size of MRPs-microcapsules (68 μm) was smaller than that of SPI-microcapsules (91 μm). The viable counts of L. reuteri in simulated gastrointestinal digestion and after storage for 30 days were improved. The modifications with Maillard reaction can improve emulsification, foaming, and gel strength of SPI, and MRPs could be used as a new type of wall material in the production of L. reuteri microcapsules.

In this study, the inhibitory activities of eight caffeoylquinic acids (CQAs) against xanthine oxidase (XOD) in vitro were investigated, and the interaction mechanisms between each compound and XOD were studied. HPLC and fluorescence spectra showed that the inhibitory activities of dicaffeoylquinic acids (diCQAs) were higher than that of monocaffeoylquinic acids (monoCQAs), due to the main roles of hydrophobic interaction and hydrogen bond between XOD and diCQAs. Both the binding constant and the lowest binding energy data indicated that the affinities of diCQAs to XOD were stronger than that of monoCQAs. Circular dichroism showed that the structure of XOD was compacted with the increased of α-helix content, resulting in decreased enzyme catalytic activity. Molecular docking revealed that CQAs preferentially bind to the flavin adenine dinucleotide region in XOD. These results provided the mechanisms of CQAs on inhibiting XOD and the further utilization of CQAs as XOD inhibitors to prevent hyperuricemia.

This paper studies the strategic channel decision-making of fresh agricultural product enterprises from the perspective of consumer convenience preferences. This research is carried out under the background of the upgrading of domestic consumption and the explosion of stay-at-home economy in China in recent years. In this paper, consumers are segmented firstly according to their different preference for consumption time, namely, convenience preference. Then, a channel decision model which considers the consumer convenience sensitivity and the inconvenience cost is proposed. Finally, the optimal wholesale price and delivery lead time of the supplier and the service level decision of the retailer are obtained by using backward induction method. The results show that under different market conditions, the supplier can adopt three equilibrium strategies: NR (No Retailer), CP (Capture Profit) and SP (Share Profit). With the change of inconvenience cost, the equilibrium state of supply chain will also change. Fresh agricultural product companies can choose different strategies to maximize their revenue according to different markets.

Real-time in situ monitoring of low-abundance cancer biomarkers (e.g., miRNAs and proteins) in living cells by nonenzymatic assembly entirely from original DNA probes remains unexplored due to an extremely complex intracellular environment. Herein, a nonenzymatic palindrome-catalyzed DNA assembly (NEPA) technique is developed to execute the in situ imaging of intracellular miRNAs by assembling a three-dimensional nanoscale DNA spherical structure (NS) with low mobility from three free hairpin-type DNAs rather than from DNA intermediates based on the interaction of designed terminal palindromes. Target miRNA was detected down to 1.4 pM, and its family members were distinguished with almost 100% accuracy. The subcellular localization of NS products can be visualized in real time. The NEPA-based sensing strategy is also suitable for the intracellular in situ fluorescence imaging of cancer-related protein receptors, offering valuable insight into developing sensing protocols for understanding the biological function of vital biomolecules in disease pathogenesis and future therapeutic applications.

Under the premise that financing constraints frequently occur in the supply chain, this paper investigates the financing model of the supplier providing guarantee for the retailer under symmetric and asymmetric information. The optimal solutions of the retailer, the supplier, and the bank are studied by using the Stackelberg game. Results show that increasing the supplier's guarantee proportion can effectively improve the bank's reasonable margin rate and increase the supplier's profit. Under the condition of asymmetric information, the bank can increase the probability of credit loan in the supply chain by reducing the cost of spot check and setting up a reasonable fine limit.

It is of great importance to design and fabricate heterojunction photocatalysts to improve photocatalytic performance. In this work, a novel ZIF-67/AgCl/Ag heterojunction photocatalyst was successfully synthesized by a facile chemical etching, deposition–precipitation, light-induced reduction approach. After chemical etching by a AgNO3 precursor, the crystal size of ZIF-67 decreased remarkably together with the replacement of Co2+ in the framework of ZIF-67 by Ag+ via surface ion exchange. As a result, optical and electrochemical measurements indicated that the separation efficiency of light-induced electrons and holes obviously increased due to the formation of a ZIF-67/AgCl/Ag heterojunction and the surface plasmon resonance of Ag0. Meanwhile, the corresponding kinetic rate constant of ZIF-67/AgCl/Ag was estimated to be 0.1615 min−1, which was 17, 7.76 and 2.67 times as high as that of individual ZIF-67, AgCl and ZIF-67/AgCl, respectively. The ZIF-67/AgCl/Ag photocatalyst also exhibited good stability and reusability in the process of photodegradation. This work demonstrated a high efficiency photocatalyst for providing new sights into the preparation of a highly efficient MOF-based heterojunction photocatalyst and its potential applications in water purification.

Flowers have developed different strategies to attract pollinators through visual or olfactory signals. Most flowers offer pollinators a reward (e.g. nectar and pollen) for the pollination service. However, one‐third of Orchidaceae have been shown not to provide a reward. Calanthe are terrestrial orchids distributed throughout China, Nepal, Japan and tropical Asia. Despite its high diversity, the pollination biology of Calanthe remains largely unknown, even though it is an important aspect of plant conservation. In the study, through field surveying, there were three Hesperiidae butterflies pollinating two species of Calanthe and the pollination behavior differed between the two species of Calanthe, which might lead to different fruit setting rates. There was no nectar in the flowers of the two species, indicating deceptive pollination. Using a glass cylinder experiment, it was deduced that the two species of Calanthe were most likely to attract pollinators by generalized food deception. Interestingly, Hesperiidae butterflies were traditionally thought to be nectar thieves and generally do not transmit pollinia. However, our findings showed that, in this case, the thieves were deceived by the plants and pollinated them for free.

Purpose The purpose of this paper is to analyze how social networking services (SNSs) affect consumers’ behaviors on the omni-channel supply chain by using a reverse research method. Design/methodology/approach Initially, a questionnaire was administered to obtain data on the relationship between the perception factors of channels and consumer behavior. Subsequently, a structural equation model was constructed, and consumer behavior were determined in the omni-channel supply chain. Finally, the importance of various factors that affected consumer behavior in the omni-channel supply chain under SNSs was determined. Findings Conclusions affirm that a positive effect on consumer channel behaviors occurs when buyers obtain information from social network platforms. However, regardless of online, offline, or mobile terminal, shortcomings are indicated in consumers’ lack of feedback on purchased goods and the bias of feedback. Originality/value The study explored ways to efficiently apply SNSs in building the omni-channel supply chain. Meanwhile, corresponding suggestions were provided such that companies will know about consumer needs.

BACKGROUND Acquired factor V deficiency is a rare secondary hemorrhagic disease, which can lead to a severe bleeding disorder. CASE SUMMARY We report a 47-year-old hemodialysis patient who presented with severe hemorrhagic pleural effusion and hemorrhagic pericardial effusion associated with lymphatic leakage. The laboratory examination revealed decreased factor V activity (2% of population average value). With decreased lymphatic leakage, factor V activity increased (to 46%). Lymph drainage correlated with prothrombin time and active partial thrombin time. The cause of the disease favored an acquired disease. The common causes which trigger factor V inhibitors were excluded. An inhibitor was not detected. It is possible that there was a clotting factor inhibitor leaking with the lymph in the drainage. Inhibitor production may be due to immune dysfunction caused by persistent lymphatic drainage, or that coagulation inhibitors were produced, drained with the lymph, and partly cleared by hemodialysis. CONCLUSION In this case, we have firstly reported factor V deficiency associated with lymphatic leakage in a hemodialysis patient.

MicroRNAs (miRs) are a class of non-coding, small RNA molecules that play important roles in gene expression. The aberrant expression of miRs is associated with various human diseases, and miRs have been regarded as biomarkers and therapeutic targets in cancer treatment. In this work, using miR-21 as model target species, an efficiently self-enhanced rolling circle amplification (seRCA)-based biosensing platform was developed for the ultrasensitive detection of cancer-related miRs. In the presence of target, a linear DNA template can be cyclized by ligase and initiate the first RCA (fRCA) reaction. Without any separation step and chemical modification, the fRCA products (fRCAp) are capable of activating the second exponential RCA and produce a much higher fluorescence signal, causing the self-enhancement effect of RCA reaction. Because two different signal amplification processes are introduced, there are two linear dynamic ranges together over 7 orders of magnitude. Target miR can be detected down to 1.0 fM with very high specificity, eliminating the interference from homologous miRs. If a fluorescently modified oligonucleotide probe is involved, the seRCA-based biosensing strategy is able to be employed for the intracellular imaging of cancer-related miR. Significantly, the comparative evaluation demonstrates that the proposed strategy exhibits the impressive capability to execute the miR imaging within cells higher than classical fluorescence in situ hybridization (FISH) method. The newly-developed powerful sensing strategy for the specific miR imaging would offer a unique opportunity to promote molecular biological research, early diagnosis and treatment of human cancers.

OBJECTIVE Hyperglycemia increases the risk of early recurrence and high mortality in some adult blood cancers. In response to increased glucose levels, insulin is secreted, and several studies have shown that insulin-induced AKT signaling can regulate tumor cell proliferation and apoptosis. The AKT pathway is aberrantly activated in adult acute lymphoblastic leukemia (ALL), but the mechanisms underlying this activation and its impact in pediatric patients with ALL are unclear. MATERIALS AND METHODS We evaluated the insulin-induced chemoresistance and AKT pathway activation by measuring cell proliferation, apoptosis, and other parameters in ALL cell lines (Jurkat and Reh cells), as well as in primary pediatric leukemic cell samples, after culture with insulin, the chemotherapeutic drugs daunorubicin (DNR), vincristine (VCR), and L-asparaginase (L-Asp), or anti-insulin-like growth factor-1 receptor (IGF-1R) monoclonal antibody. RESULTS DNR, VCR, and L-Asp-induced toxicity in Jurkat and Reh cells was reduced in the presence of insulin. DNR promoted cell proliferation, whereas DNR, VCR, and L-Asp all reduced apoptosis in both cell lines cotreated with insulin compared with that in cell lines treated with chemotherapeutics alone (P

We propose a quantized Majorana pump (QMP) in semiconductor-superconductor heterostructures. The pump consists of a Majorana nanowire, i.e., a Rashba wire in proximity to an $s$-wave superconductor and in a magnetic field, and two ferromagnetic leads. When the orientation of the magnetic field is rotated by $2\ensuremath{\pi}$, an elementary charge $e$ is transferred between two leads. The number of the pumped charge in a cycle is related to the winding number of the Andreev reflection amplitude. In the topologically trivial phase without Majorana zero mode (MZM), the pumped charge decreases rapidly to zero. More importantly, the pump works at zero bias and provides a more effective way to distinguish MZMs from trivial partially separated Andreev bound states. Therefore, this QMP provides not only a smoking-gun signature of MZMs, but also an ideal platform to realize topological single-electron pumps with the potential for realizing novel current standards in electrical metrology.

DNA nanotechnology can be used to precisely construct nanostructures of different shapes, sizes and surface chemistry, which is appreciated in a variety of areas such as biomaterials, nanodevices, disease diagnosis, imaging, and drug delivery. Enzymatic degradation resistance and cell-targeting capability are indispensable for the applications of DNA nanostructures in biological and biomedical fields, and is challenging to rationally design the desirable nanoscale DNA materials suitable for the clinical translation by the existing assembly methodologies. Herein, we present a simple and efficient method for the hierarchical assembly of a three-level DNA ring-based nanostructure (DNA h-Nanoring) in a precise order, where DNA compositions at the primary level, the second level and the third level are a single DNA ring, two-ring-hybridized duplex and uniform complex macro-cycle, respectively. Most as-assembled DNA h-Nanorings exhibit the regular two-dimensional cycle-shaped structure characterized by atomic force microscopy (AFM). The Nanoring exhibits a significantly enhanced resistance to enzymatic attack, such that it can remain intact in 10% fetal bovine serum (FBS) for 24 h, and even stably exist in the presence of nuclease at a high concentration. More importantly, it is very easy to modify the DNA h-Nanoring with functional moieties (e.g., targeting ligand aptamer) because there are many single-stranded fragments available for further hybridization. By combining with receptor-targeted Sgc8, the nanoring can be used to accomplish the cell imaging and criminate target CEM cells from control cells, demonstrating a potential platform for in vivo tumor imaging and targeted chemotherapeutics delivery.

Background Chinese te-flavor baijiu (CTF), the most famous Chinese baijiu in Jiangxi province, China, is made from a unique daqu. Its characteristic style is closely related to the daqu used for fermentation. However, current studies on the effects of different production seasons on microbial communities, physicochemical indices, and volatile compounds in CTF daqu are very rare. Results The relationships of microbial communities, physicochemical indices, and volatile compounds in CTF daqu produced in summer (July and August) and autumn (September and October) were studied. The results of Illumina MiSeq sequencing indicated that there was greater bacterial diversity in the CTF daqu-7 (produced in July) and CTF daqu-8 (produced in August) and greater fungal diversity in the CTF daqu-9 (produced in September) and CTF daqu-10 (produced in October). The physicochemical indices of CTF daqu produced in different seasons were significantly different. It was determined that CTF daqu-9 had the highest esterification and liquefaction abilities. A total of 44 volatile compounds, including alcohols, esters, aldehydes, and ketones were identified in CTF daqu produced during different seasons. Among them, CTF daqu-9 had the greatest alcohol content. Conclusion September (early autumn) is the best production period for CTF daqu. The results of the study provide a theoretical basis for the standardized and uniform production of Chinese baijiu. © 2021 Society of Chemical Industry.