MAGP1 maintains tumorigenicity and angiogenesis of laryngeal cancer by activating Wnt/ß-catenin/MMP7 pathway.

Microfibril-associated glycoprotein-1 (MAGP1), a crucial extracellular matrix protein, contributes to the initiation and progression of different cancers. However, the role of MAGP1 in laryngeal cancer is not clear. The purpose of this study was to investigate the clinical significance and biological function of MAGP1 in laryngeal cancer. MAGP1 was upregulated in public databases and laryngeal cancer tissues, and high MAGP1 expression led to a poor prognosis and was identified as an independent prognostic marker. Knocking-down MAGP1 inhibited laryngeal cancer cell growth and metastasis. According to gene set enrichment analysis, high MAGP1 expression revealed enrichment in Wnt/ß-catenin signaling and knocking-down MAGP1 in laryngeal cancer cells also caused degradation, de-activation, re-location and loss of stability of ß-catenin. Additionally, we observed MAGP1 in laryngeal cancer cells inhibits angiogenesis in an MMP7-dependent way. In conclusion, our study suggests a clinical role of MAGP1 in laryngeal cancer, signifying its potential as a therapeutic target in the future.

Associations between anxiety, depression, and personal mastery in community-dwelling older adults: a network-based analysis.

BACKGROUND: In China, about 18.70% of the population aged 60 years and older are at risk of low personal mastery as well as anxiety and depression for a variety of reasons. The purpose of this study was to construct a symptom network model of the relationship between anxiety, depression, and personal mastery in community-dwelling older adults and to identify central and bridge symptoms in this network. METHODS: Depression, anxiety, and personal mastery were measured using the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7), and Personal Mastery Scale (PMS), respectively. A total of 501 older adults in 16 communities in Changzhou and Zhenjiang, Jiangsu Province, China, were surveyed by using a combination of stratified sampling and convenience sampling methods. The R language was used to construct the network. RESULTS: (1) The network structure of anxiety-depression-personal mastery was stable, with "Nervousness" (node GAD1, strength = 1.38), "Sad mood" (node PHQ2, strength = 1.22), " Inability to change" (node PMS2, strength = 1.01) and "Involuntarily" (node PMS3, strength = 0.95) as the central symptoms. (2) "Irritability" (node GAD6, bridge strength = 0.743), "Sad mood" (node PHQ2, bridge strength = 0.655), and "Trouble relaxing" (node GAD4, bridge strength = 0.550) were the bridge symptoms connecting anxiety, depressive symptoms, and personal mastery. (3) In the network comparison test (NCT), residence, somatic chronic comorbidity and gender had no significant effect on network structure. CONCLUSIONS: The construction of the anxiety-depression-personal mastery network structure opens up new possibilities for mechanisms of action and intervention formulation for psychological disorders in community-dwelling older adults. The identification of central symptoms (e.g., nervousness, sad mood, inability to change, involuntarily) and bridge symptoms (e.g., irritability, sad mood, trouble relaxing) in community-dwelling older adults with anxiety, depression, and low sense of mastery can provide a scientific basis for the development of precise interventions.

Development and validation of a noninvasive prediction model for significant hepatic liver fibrosis in Chinese patients with autoimmune hepatitis.

INTRODUCTION AND OBJECTIVES: Autoimmune hepatitis (AIH) is a prevalent noninfectious liver disease. However, there is currently a lack of noninvasive tests appropriate for evaluating liver fibrosis in AIH patients. The objective of this study was to develop and validate a predictive model for noninvasive assessment of significant liver fibrosis (S ≥ 2) in patients to provide a reliable method for evaluating liver fibrosis in individuals with AIH. MATERIALS AND METHODS: The clinical data of 374 AIH patients were analyzed. A prediction model was established through logistic regression in the training set, and bootstrap method was used to validate the models internally. In addition, the clinical data of 109 AIH patients were collected for external verification of the model.The model was expressed as a nomogram, and area under the curve (AUC) of the receiver operating characteristic (ROC), calibration curve, and decision curve analysis were used to evaluate the accuracy of the prediction model. RESULTS: Logistic regression analysis revealed that age, platelet count (PLT), and the A/G ratio were identified as independent risk factors for liver fibrosis in AIH patients (P < 0.05). The diagnostic model that was composed of age, PLT and A/G was superior to APRI and FIB-4 in both the internal validation (0.872, 95%CI: 0.819-0.924) and external validation (0.829, 95%CI: 0.753-0.904). CONCLUSIONS: Our predictive model can predict significant liver fibrosis in AIH patients more accurately, simply, and noninvasively.

Sensitive and Specific Loop-Mediated Isothermal Amplification Assays for Detection of Salmonella, CTX-M-1 Group Genes, mph(A), and ermB in Stool and Blood Samples Based on Orange to Green Visible Dye.

Salmonella is a globally prevalent foodborne bacterium, and ceftriaxone and azithromycin have been regarded as drugs of choice for treating Salmonella infections, particularly in children. With the growing incidence of ceftriaxone and azithromycin resistance in Salmonella, there is an urgent requirement for a rapid and dependable gene testing approach to enhance the efficacy of treating Salmonella infections. Utilizing the orange to green visible dye approach, this study developed loop-mediated isothermal amplification (LAMP) assays for the sensitive and specific detection of Salmonella, ceftriaxone and azithromycin resistance genes (including CTX-M-1 group, mph(A), and ermB genes) in stool and blood samples. The specificity and sensitivity of primers during the LAMP assays for detection of Salmonella, CTX-M-1 group, mph(A), and ermB genes were determined in this study. The detection threshold for Salmonella was found to be 1.5 × 103 colony-forming units (CFU)/mL, while it was 1.5 × 102 CFU/mL for CTX-M-1 group genes (including blaCTX-M-3, blaCTX-M-15, and blaCTX-M-55), 1.5 × 102 CFU/mL for mph(A), and 1.5 × 102 CFU/mL for ermB, showing 10-103-fold, 103-fold, and 105-fold increased sensitivity compared with the polymerase chain reaction assay, respectively. Results indicated that the LAMP primers designed for Salmonella, CTX-M-1 group, mph(A), and ermB genes possess high specificity (100%) and sensitivity (over 94%). This novel approach advocates its application in detecting Salmonella, CTX-M-1 group, mph(A), and ermB genes.

Sensitive and rapid detection of tet(X2) ~ tet(X5) by loop-mediated isothermal amplification based on visual OTG dye.

The emergence of tigecycline-resistant tet(X2/X3/X4/X5) genes poses a new threat to the efficacy of anti-infective therapy and the safety of our food and environment. To control the transfer of such genes, a sensitive and rapid molecular method is warranted to detect tet(X2/X3/X4/X5) genes in clinical isolates. Herein, we established a loop-mediated isothermal amplification (LAMP) assay to rapidly detect tet(X2/X3/X4/X5) genes, and the results were assessed by chromogenic visualization. The specificity and sensitivity of the primers during the LAMP assay for the simultaneous detection of tet(X2/X3/X4/X5) genes were determined in this study. All 48 clinical strains without tet(X2/X3/X4/X5) genes yielded negative results during the LAMP assay, substantiating the high specificity of the LAMP primers. The detection thresholds of this assay were 1.5 × 102 CFU/ml and 0.2 fg/uL corresponding to a 10 to 100-fold and 100-fold increase in sensitivity compared to polymerase chain reaction (PCR) assays. Out of 52 bacterial strains tested, using PCR as a reference, our research revealed that the LAMP assay demonstrated a sensitivity and specificity of 100%. To sum up, our novel approach has huge prospects for application in the simultaneous detection of tet(X2/X3/X4/X5) genes and can be applied to detect other drug-resistance genes.

Exploring the dynamics of perioperative symptom networks in colorectal cancer patients: a cross-lagged panel network analysis.

BACKGROUND: Colorectal cancer incidence is on the rise, necessitating precise symptom management. However, causal relationships among symptoms have been challenging to establish due to reliance on cross-sectional data. Cross-lagged panel network (CLPN) analysis offers a solution, leveraging longitudinal data for insight. OBJECTIVE: We employed CLPN analysis to construct symptom networks in colorectal cancer patients at three perioperative time points, aiming to identify predictive relationships and intervention opportunities. METHODS: We evaluated the prevalence and severity of symptoms throughout the perioperative period, encompassing T1 the first day of admission, T2 2-3 days postoperatively, and T3 discharge, utilizing the M. D. Anderson Symptom Inventory Gastrointestinal Cancer Module (MDASI-GI). To identify crucial nodes in the network and explore predictive and interactive effects among symptoms, CLPNs were constructed from longitudinal data in R. RESULTS: The analysis revealed a stable network, with disturbed sleep exhibiting the highest out-EI (outgoing expected influence) during T1. Distress had a sustained impact throughout the perioperative. Disturbed sleep at T1 predicted T2 bloating, fatigue, distress, and pain. T1 distress predicted T2 sadness severity. T2 distress primarily predicted T3 fatigue, disturbed sleep, changes in taste, and bloating. T2 shortness of breath predicted T3 changes in taste and loss of appetite. Furthermore, biochemical markers like RBC and ALB had notable influence on symptom clusters during T1→T2 and T2→T3, respectively. CONCLUSION: Prioritizing disturbed sleep during T1 and addressing distress throughout the perioperative phase is recommended. Effective symptom management not only breaks the chain of symptom progression, enhancing healthcare impact, but also eases patient symptom burdens.

Diagnostic value of endoscopic ultrasonography in periampullary duodenal tumours.

Introduction: The objective of this study was to investigate the diagnostic value of endoscopic ultrasonography (EUS) for tumours around the duodenal ampullary. Patients and Methods: A retrospective analysis was performed on cases diagnosed and treated in our hospital from October 2016 to August 2021 due to the lesions around the duodenal ampulla. All patients received EUS, abdominal enhanced computed tomography (CT) and magnetic resonance imaging combined with magnetic resonance cholangiopancreatography (MRI-MRCP). Pathological diagnosis was used to verify the accuracy of the imaging findings. The detection rates of periampullary tumours by EUS, abdominal enhanced CT and MRI-MRCP were determined and compared. Results: A total of 86 patients were included in this study. According to the pathological diagnosis, the detection rate of EUS was 87% (36/41) for periampullary tumour lesions with a tumour diameter <1 cm, which was significantly higher than that of MRI-MRCP (59%, 24/41) (P = 0.003) and CT (44%, 18/41) (P < 0.001). For periampullary tumour lesions with a tumour diameter ≥1 cm, the detection rate of MRI-MRCP was 93% (42/45), which was significantly higher than that of EUS (78%, 35/45) (P = 0.036) and CT (76%, 34/45) (P = 0.02). Conclusions: EUS can accurately detect tumour lesions around the ampullary part of the duodenum with minimal gas interference. For periampullary tumour lesions <1 cm, EUS has better diagnostic accuracy than abdominal-enhanced CT and MRI-MRCP. In addition, a biopsy of the lesion can be performed at the same time during the EUS examination. Therefore, EUS has an important clinical significance and value in the diagnosis of duodenal periampullary tumours.

A Molten-Salt Method to Synthesize Ultrahigh-Nickel Single-Crystalline LiNi0.92 Co0.06 Mn0.02 O2 with Superior Electrochemical Performance as Cathode Material for Lithium-Ion Batteries.

Ni-rich layered oxides have been intensively considered as promising cathode materials for next-generation Li-ion batteries. Nevertheless, the performance degradation caused by intergranular cracks and electrode/electrolyte interface parasitic reactions restricts their further application. Compared with secondary particles, single-crystal (SC) materials have better mechanical integrity and cycling stability. However, the preparation of ultrahigh-nickel layered SC cathode still remains a serious challenge. Herein, a novel LiOH-LiNO3 -H3 BO3 molten-salt method is proposed to synthesize SC LiNi0.92 Co0.06 Mn0.02 O2 with considerable crystallinity and uniformity. The critical impacts of calcination temperature and boric acid on the microstructure and electrochemical property of Ni-rich layered oxides are systematically investigated. The results show that the crystal growth is promoted and the stability of crystal structure is improved by this synthesis method. In particular, the optimal electrode demonstrates a superior initial discharge capacity of 214.8 mAh g-1 with a high capacity retention of 86.3% over 300 cycles as tested by pouch-type full cells at 45 ºC. This work not only prepares an ultrahigh-nickel layered CS cathode with superior electrochemical performances, but also provides a feasible method for the synthesis of other CS layered cathode materials.

Lycorine inhibits angiogenesis by docking to PDGFRα.

Lycorine (Lyc) is a natural alkaloid derived from medicinal plants of the Amaryllidaceae family. Lyc has been reported to inhibit the recurrence and metastasis of different kinds of tumors. However, Lyc's effect on angiogenesis and its specific mechanism are still not clear. This study was designed to test the antiangiogenesis effect of Lyc and to explore the possible mechanisms. We performed cell experiments to confirm Lyc's inhibitory effect on angiogenesis and employed sunitinib as a positive control. Moreover, the synergistic effect of Lyc and sunitinib was also explored. Next, we conducted bioinformatics analyses to predict the potential targets of Lyc and verified them by western blotting and immunofluorescence. Molecular docking, kinase activity assays, Biacore assays and cellular thermal shift assays (CETSAs) were applied to elucidate the mechanism by which Lyc inhibited target activity. Lyc inhibited angiogenesis in human umbilical vein endothelial cells (HUVECs). Employing bioinformatics, we found that Lyc's target was PDGFRα and that Lyc attenuated PDGFRα phosphorylation. We also found that Lyc inhibited PDGFRα activation by docking to it to restrain its activity. Additionally, Lyc significantly inhibited PDGF-AA-induced angiogenesis. This study provides new insights into the molecular functions of Lyc and indicates its potential as a therapeutic agent for tumor angiogenesis.

3D printing of flexible strain sensor based on MWCNTs/flexible resin composite.

The flexible strain sensor is an indispensable part in flexible integrated electronic systems and an important intermediate in external mechanical signal acquisition. The 3D printing technology provides a fast and cheap way to manufacture flexible strain sensors. In this paper, a MWCNTs/flexible resin composite for photocuring 3D printing was prepared using mechanical mixing method. The composite has a low percolation threshold (1.2%ωt). Based on the composite material, a flexible strain sensor with high performance was fabricated using digital light processing technology. The sensor has a GF of 8.98 under strain conditions ranging between 0% and 40% and a high elongation at break (48%). The sensor presents mechanical hysteresis under cyclic loading. With the increase of the strain amplitude, the mechanical hysteresis becomes more obvious. At the same time, the resistance response signal of the sensor shows double peaks during the unloading process, which is caused by the competition of disconnection and reconstruction of conductive network in the composite material. The test results show that the sensor has different response signals to different types of loads. Finally, its practicability is verified by applying it to balloon pressure detection.

Establishment and validation of nomogram for predicting immuno checkpoint inhibitor related pneumonia.

OBJECTIVE: Cancer is one of the main causes of death worldwide. Although immunotherapy brings hope for cancer treatment, it is also accompanied by immune checkpoint inhibitor-related adverse events (irAEs). Immune checkpoint inhibitor pneumonia (CIP) is a potentially fatal adverse event, but there is still a lack of effective markers and prediction models to identify patients at increased risk of CIP. METHODS: A total of 369 cancer patients treated between 2017 and 2022 with immune checkpoint inhibitors at Shengjing Hospital of China Medical University and Liaoning People's Hospital were recruited for this study. Independent variables were selected by differences and binary logistic regression analysis, and a risk assessment nomogram was constructed for CIP risk. The accuracy and discriminative abilities of the nomogram were evaluated by calibration plots, receiver operating characteristic curves (ROCs) and decision curve analyses (DCAs). RESULTS: Binary logistic regression analysis showed that smoking history, acute phase proteins [interleukin (IL-6) and C-reactive protein (CRP)], CD8 + T lymphocyte count and serum alveolar protein [surface protein-A (SP-A) and Krebs Von den Lungen-6 (KL-6)] were significantly associated with CIP risk. A nomogram consisting of these variables was established and validated by different analyses. CONCLUSIONS: We developed an effective risk nomogram for CIP prediction in immune-checkpoint inhibitor administrated cancer patients, which will further assist early detection of immunotherapy-related adverse events.

Bufalin inhibits human diffuse large B-cell lymphoma tumorigenesis by inducing cell death through the Ca2+/NFATC1/cMYC pathway.

The 5-year survival rate of diffuse large B-cell lymphoma (DLBCL) can reach 60%. However, nearly half of patients undergo relapse/refractory issues with a survival period of less than 2 years. New therapeutic approaches are therefore needed to improve chemotherapy efficacy and patient survival. Bufalin (BF), isolated from the traditional Chinese medicine Chansu, has been reported to play an anticancer role in multiple cancer cell types. However, there are few reports of the effects of BF on the growth of DLBCL. In the present study, we demonstrated that BF exerts antitumor activity in DLBCL cells, both in vitro and in vivo. Treatment of DLBCL cells with BF resulted in increased proliferation and apoptosis in a dose- and time-dependent manner. Daily intraperitoneal injection of 1.5 mg/kg BF significantly delayed DLBCL xenograft growth in NOD/SCID mice without affecting body weight. Bioinformatics analysis showed that BF may regulate NFATC1 protein and affect expression of its downstream gene, cMYC. Our results suggest that BF can attenuate NFATC1 translocation by reducing the intracellular calcium concentration; BF may also have a low synergistic effect with cyclosporin A. In conclusion, we demonstrated that BF exerts antitumor activity that is mediated at least in part by the Ca2+/NFATC1/cMYC pathway. Our findings suggest that BF can be effectively applied as a novel potential therapeutic agent for DLBCL.

WRKY44 represses expression of the wound-induced sesquiterpene biosynthetic gene ASS1 in Aquilaria sinensis.

Agarwood is derived from wounds in Aquilaria trees and is widely used in traditional medicine, incense, and perfume. Sesquiterpenes are one of the main active components in agarwood and are known to be induced by wounding or injury; However, the molecular mechanisms by which wounding leads to sesquiterpene formation remain largely unknown. Agarwood sesquiterpene synthase 1 (ASS1) is one of key enzymes responsible for the biosynthesis of sesquiterpenes and is a crucial jasmonate (JA)-responsive wound-inducible synthase. However, it is not known why ASS1 is not expressed in healthy trees and how its expression is induced as a result of wounding. Here, we report that ASS1 is a wound-induced gene with a promoter in which a 242-bp region (-973 to -731bp) is identified as the core sequence for responding to wound signals. AsWRKY44 binds directly to this region and represses ASS1 promoter activity. Down-regulation or disruption of AsWRKY44 can relieve the inhibition and activate ASS1 expression. In addition, AsWRKY44 is degraded and the expression of ASS1 is significantly up-regulated in response to exogenous application of methyl jasmonate. Thus, AsWRKY44 is a crucial negative regulator of wound-induced ASS1 transcription, and is central to the mechanism of sesquiterpene biosynthesis in agarwood.

Piperlongumine inhibits head and neck squamous cell carcinoma proliferation by docking to Akt.

Piperlongumine (PL) is a biologically active alkaloid isolated from the long pepper roots and widely used as a traditional medicine in Ayurvedic medicine. However, the mechanism of PL's effect on head and neck squamous cell carcinoma (HNSCC) is not well understood. We performed cell experiments to confirm PL's inhibitory effect on HNSCC and employing cisplatin as positive control. Next, we conducted bioinformatics to predict PL's potential targets and verified by western blotting. Molecular docking, Biacore experiment and kinase activity assays were applied to elucidate the mechanism by which PL inhibited target activity. In vivo efficacy was verified by xenotransplantation and immunohistochemistry. PL inhibited proliferation, promoted late apoptosis, arrested cell cycle and inhibited DNA replication of the HEp-2 and FaDu cell lines. Employing bioinformatics, we found that PL's target was Akt and PL attenuated Akt phosphorylation. We found from molecular docking, Biacore experiment and kinase activity assay that PL inhibited Akt activation by docking to Akt to restrain its activity. In addition, PL significantly inhibited the growth of xenograft tumors by down regulating the expression of p-Akt in vivo. This study provides new insights into the molecular functions of PL and indicate its potential as a therapeutic agent for HNSCC.

Clinicopathological implications of TIM3+ tumor-infiltrating lymphocytes and the miR-455-5p/Galectin-9 axis in skull base chordoma patients.

Chordoma is difficult to eradicate due to high local recurrence rates. The immune microenvironment is closely associated with tumor prognosis; however, its role in skull base chordoma is unknown. The expression of Galectin-9 (Gal9) and tumor-infiltrating lymphocyte (TIL) markers was assessed by immunohistochemistry. Kaplan-Meier and multivariate Cox analyses were used to assessing local recurrence-free survival (LRFS) and overall survival (OS) of patients. MiR-455-5p was identified as a regulator of Gal9 expression. Immunopositivity for Gal9 was associated with tumor invasion (p = 0.019), Karnofsky performance status (KPS) score (p = 0.017), and total TIL count (p < 0.001); downregulation of miR-455-5p was correlated with tumor invasion (p = 0.017) and poor prognosis; and the T-cell immunoglobulin and mucin-domain 3 (TIM3)+ TIL count was associated with chordoma invasion (p = 0.010) and KPS score (p = 0.037). Furthermore, multivariate analysis indicated that only TIM3+ TIL density was an independent prognostic factor for LRFS (p = 0.010) and OS (p = 0.016). These results can be used to predict clinical outcome and provide a basis for immune therapy in skull base chordoma patients.

Stretch-induced complexation reaction between poly(vinyl alcohol) and iodine: an in situ synchrotron radiation small- and wide-angle X-ray scattering study.

Fibrillation and the complexation reaction between poly(vinyl alcohol) (PVA)-iodine (i) complexes have been studied with in situ synchrotron radiation small- and wide-angle X-ray scattering (SAXS and WAXS) during the uniaxial stretching of PVA films in KI/I2 aqueous solution. SAXS results show that stretching induces the formation of nanofibrils, which pack periodically in the later stage of stretching with an average inter-fibrillar distance of around 10 nm. The onset strains for fibrillation and the appearance of periodicity of nanofibrils are located at the beginning and the end of the stress plateau, and decrease with increasing iodine concentration. In the stretching process as a whole, the presence of iodine ions reduces the crystallinity of the PVA crystal but favors the formation of a PVA-I complex. The complexation reaction is promoted by the synergistic effect of stretch and iodine ions, during which stretching drives the formation of polyiodine via the effect of entropic reduction while iodine concentration dictates crystallization of PVA-I3- co-crystals through the role of chemical potential. A morphological and structural phase diagram is constructed in the strain-iodine concentration space, which defines the regions for fibrillation and complexation reactions and may serve as a roadmap for the industrial processing of PVA polarizer.

Hyperspectral Image Classification Based on Improved Rotation Forest Algorithm.

Hyperspectral image classification is a hot issue in the field of remote sensing. It is possible to achieve high accuracy and strong generalization through a good classification method that is used to process image data. In this paper, an efficient hyperspectral image classification method based on improved Rotation Forest (ROF) is proposed. It is named ROF-KELM. Firstly, Non-negative matrix factorization( NMF) is used to do feature segmentation in order to get more effective data. Secondly, kernel extreme learning machine (KELM) is chosen as base classifier to improve the classification efficiency. The proposed method inherits the advantages of KELM and has an analytic solution to directly implement the multiclass classification. Then, Q-statistic is used to select base classifiers. Finally, the results are obtained by using the voting method. Three simulation examples, classification of AVIRIS image, ROSIS image and the UCI public data sets respectively, are conducted to demonstrate the effectiveness of the proposed method.

Transcription Factor AsMYC2 Controls the Jasmonate-Responsive Expression of ASS1 Regulating Sesquiterpene Biosynthesis in Aquilaria sinensis (Lour.) Gilg.

Sesquiterpenes are one of the most important defensive secondary metabolite components of agarwood. Agarwood, which is a product of the Aquilaria sinensis response to external damage, is a fragrant and resinous wood that is widely used in traditional medicines, incense and perfume. We previously reported that jasmonic acid (JA) plays an important role in promoting agarwood sesquiterpene biosynthesis and induces expression of the sesquiterpene synthase ASS1, which is a key enzyme that is responsible for the biosynthesis of agarwood sesquiterpenes in A. sinensis. However, little is known about this molecular regulation mechanism. Here, we characterized a basic helix-loop-helix transcription factor, AsMYC2, from A. sinensis as an activator of ASS1 expression. AsMYC2 is an immediate-early jasmonate-responsive gene and is co-induced with ASS1. Using a combination of yeast one-hybrid assays and chromatin immunoprecipitation analyses, we showed that AsMYC2 bound the promoter of ASS1 containing a G-box motif. AsMYC2 activated expression of ASS1 in tobacco epidermis cells and up-regulated expression of sesquiterpene synthase genes (TPS21 and TPS11) in Arabidopsis, which was also promoted by methyl jasmonate. Our results suggest that AsMYC2 participates in the regulation of agarwood sesquiterpene biosynthesis in A. sinensis by controlling the expression of ASS1 through the JA signaling pathway.

Cold-Inducible RNA-Binding Protein Regulates Cardiac Repolarization by Targeting Transient Outward Potassium Channels.

RATIONALE: Cold-inducible RNA-binding protein (CIRP) is constitutively expressed at low levels across various tissues. It is rapidly upregulated by multiple stresses, underlying a general role for CIRP in organic adaptations to pathophysiological conditions. However, the role of CIRP in the heart remains unclear. OBJECTIVE: To examine the biofunctions of CIRP in the mammalian heart. METHODS AND RESULTS: Rats with targeted disruption of Cirp were generated using the TALEN (transcription activator-like effector nucleases)-based genome editing technique. The Cirp-knockout rats had structurally and functionally normal hearts. Resting ECG recordings revealed a short rate-corrected QT (QTc) interval in Cirp-null rats without any abnormalities in PR interval, RR interval or QRS waves as compared to wild-type animals. The shortened QTc interval from Cirp ablation was tightly linked to an abbreviated action potential duration in cardiac myocytes, which was attributable to increased transient outward potassium current (Ito). Furthermore, our findings uncovered that CIRP protein selectively bonded to KCND2 and KCND3 mRNAs encoding the functional α-subunits of Ito channel proteins. CIRP deficiency did not change the transcriptional activity of KCND2 or KCND3, but it facilitated their translation. Cirp knockout had no effect on the functional expression of ion channels other than Ito channels. CONCLUSIONS: CIRP modulates cardiac repolarization by negatively adjusting the expression and function of Ito channels. Our study may open a window to decipher the potential function of RNA-binding proteins in bioelectric activity.

The effect of nilotinib plus arsenic trioxide on the proliferation and differentiation of primary leukemic cells from patients with chronic myoloid leukemia in blast crisis.

AIM: To determine the effects of arsenic trioxide (ATO) and nilotinib (AMN107, Tasigna) alone or in combination on the proliferation and differentiation of primary leukemic cells from patients with chronic myeloid leukemia in the blast crisis phase (CML-BC). METHODS: Cells were isolated from the bone marrow of CML-BC patients and were treated with 1 µM ATO and 5 nM nilotinib, either alone or in combination. Cell proliferation was evaluated using a MTT assay. Cell morphology and the content of hemoglobin were examined with Wright-Giemsa staining and benzidine staining, respectively. The expression of cell surface markers was determined using flow cytometric analysis. The levels of mRNA and protein were analyzed using RT-PCR and Western blotting, respectively. RESULTS: ATO and nilotinib alone or in combination suppressed cell proliferation in a dose- and time-dependent pattern (P < 0.01 vs. control). Drug treatments promoted erythroid differentiation of CML-BC cells, with a decreased nuclei/cytoplasm ratio but increased hemoglobin content and glycophorin A (GPA) expression (P < 0.01 compared with control). In addition, macrophage and granulocyte lineage differentiation was also induced after drug treatment. The mRNA and protein levels of basic helix-loop-helix (bHLH) transcription factor T-cell acute lymphocytic leukemia protein 1 (TAL1) and B cell translocation gene 1 (BTG1) were both upregulated after 3 days of ATO and Nilotinib treatment. CONCLUSIONS: Our findings indicated that ATO and nilotinib treatment alone or in combination greatly suppressed cell proliferation but promoted the differentiation of CML-BC cells towards multiple-lineages. Nilotinib alone preferentially induced erythroid differentiation while combined treatment with ATO preferentially induced macrophage and granulocyte lineage differentiation.