Aggresome formation promotes ASK1/JNK signaling activation and stemness maintenance in ovarian cancer.

Aggresomes are the product of misfolded protein aggregation, and the presence of aggresomes has been correlated with poor prognosis in cancer patients. However, the exact role of aggresomes in tumorigenesis and cancer progression remains largely unknown. Herein, the multiomics screening reveal that OTUD1 protein plays an important role in retaining ovarian cancer stem cell (OCSC) properties. Mechanistically, the elevated OTUD1 protein levels lead to the formation of OTUD1-based cytoplasmic aggresomes, which is mediated by a short peptide located in the intrinsically disordered OTUD1 N-terminal region. Furthermore, OTUD1-based aggresomes recruit ASK1 via protein-protein interactions, which in turn stabilize ASK1 in a deubiquitinase-independent manner and activate the downstream JNK signaling pathway for OCSC maintenance. Notably, the disruption of OTUD1-based aggresomes or treatment with ASK1/JNK inhibitors, including ibrutinib, an FDA-approved drug that was recently identified as an MKK7 inhibitor, effectively reduced OCSC stemness (OSCS) of OTUD1high ovarian cancer cells. In summary, our work suggests that aggresome formation in tumor cells could function as a signaling hub and that aggresome-based therapy has translational potential for patients with OTUD1high ovarian cancer.

KDM5C-Mediated Recruitment of BRD4 to Chromatin Regulates Enhancer Activation and BET Inhibitor Sensitivity.

The BET family member BRD4 is a bromodomain-containing protein that plays a vital role in driving oncogene expression. Given their pivotal role in regulating oncogenic networks in various cancer types, BET inhibitors (BETi) have been developed, but the clinical application has been impeded by dose-limiting toxicity and resistance. Understanding the mechanisms of BRD4 activity and identifying predictive biomarkers could facilitate the successful clinical use of BETis. Herein, we show that KDM5C and BRD4 cooperate to sustain tumor cell growth. Mechanistically, KDM5C interacted with BRD4 and stimulated BRD4 enhancer recruitment. Moreover, binding of the BRD4 C-terminus to KDM5C stimulated the H3K4 demethylase activity of KDM5C. The abundance of both KDM5C-associated BRD4 and H3K4me1/3 determined the transcriptional activation of many oncogenes. Notably, depletion or pharmacologic degradation of KDM5C dramatically reduced BRD4 chromatin enrichment and significantly increased BETi efficacy across multiple cancer types in both tumor cell lines and patient-derived organoid models. Furthermore, targeting KDM5C in combination with BETi suppressed tumor growth in vivo in a xenograft mouse model. Collectively, this work reveals a KDM5C-mediated mechanism by which BRD4 regulates transcription, providing a rationale for incorporating BETi into combination therapies with KDM5C inhibitors to enhance treatment efficacy. SIGNIFICANCE: BRD4 is recruited to enhancers in a bromodomain-independent manner by binding KDM5C and stimulates KDM5C H3K4 demethylase activity, leading to synergistic effects of BET and KDM5C inhibitor combinations in cancer.

A bacteria-derived tetramerized protein ameliorates nonalcoholic steatohepatitis in mice via binding and relocating acetyl-coA carboxylase.

Increased de novo lipogenesis (DNL) is a major feature of nonalcoholic steatohepatitis (NASH). None of the drugs targeting the catalytic activity of acetyl-CoA carboxylase (ACC), the rate-limiting enzyme in the DNL process, have been approved by the FDA. Whether cytosolic ACC1 can be regulated spatially remains to be explored. Herein, we find that streptavidin (SA), which is a bacterium-derived tetrameric protein, forms cytosolic condensates and efficiently induces a spatial re-localization of ACC1 in liver cells, concomitant with inhibited lipid accumulation. Both SA tetrameric structure and multivalent protein interaction are required for condensate formation. Interestingly, the condensates are further characterized as gel-like membraneless organelle (SAGMO) and significantly restrict the cytosolic dispersion of ACC1 and fatty acid synthase. Notably, AAV-mediated delivery of SA partially blocks mouse liver DNL and ameliorates NASH without eliciting hypertriglyceridemia. In summary, our study shows that insulating lipogenesis-related proteins by SAGMO might be effective for NASH treatment.

Squeezing-induced nonreciprocal photon blockade in an optomechanical microresonator.

We propose a scheme to generate nonreciprocal photon blockade in a stationary whispering gallery microresonator system based on two physical mechanisms. One of the two mechanisms is inspired by recent work [Phys. Rev. Lett.128, 083604 (2022)10.1103/PhysRevLett.128.083604], where the quantum squeezing caused by parametric interaction not only shifts the optical frequency of propagating mode but also enhances its optomechanical coupling, resulting in a nonreciprocal conventional photon blockade phenomenon. On the other hand, we also give another mechanism to generate stronger nonreciprocity of photon correlation according to the destructive quantum interference. Comparing these two strategies, the required nonlinear strength of parametric interaction in the second one is smaller, and the broadband squeezed vacuum field used to eliminate thermalization noise is no longer needed. All analyses and optimal parameter relations are further verified by numerically simulating the quantum master equation. Our proposed scheme opens a new avenue for achieving the nonreciprocal single photon source without stringent requirements, which may have critical applications in quantum communication, quantum information processing, and topological photonics.

[Effect of Systematic Graded Rewarming Pattern on All-Cause Mortality of Hypothermic Trauma Patients in Different Time Periods].

Objective To investigate the effect of systematic graded rewarming pattern on all-cause mortality of hypothermic trauma patients in different time periods. Methods A prospective case-control study was carried out for 236 hypothermic trauma patients with modified trauma score<12 in the Emergency Department of the Second Affiliated Hospital of Wenzhou Medical University from January 2020 to December 2021.The patients were randomly assigned into a systematic graded rewarming group (n=118) and a traditional rewarming group (n=118).The main outcome event was all-cause death within 15 days after trauma,and the secondary outcome event was all-cause death within 3,7,and 30 days after trauma. Results Overall,13.98%(33/236) and 14.83%(35/236) of the patients died within 15 and 30 days after trauma,respectively,and the median survival time of all dead patients was 6 (4,10) days.The systematic graded rewarming group had higher temperature after rewarming for 2 h (P=0.001) and larger temperature change after rewarming intervention (P=0.047) than the traditional rewarming group.The all-cause mortality within 15 days (27.3%vs.72.7%,P=0.005) and 30 days (25.7%vs.74.3%,P=0.002) in the systematic graded rewarming group was lower than that in the traditional rewarming group.Kaplan-Meier analysis showed that the survival time of the patients in the systematic graded rewarming group was longer than that in the traditional rewarming group (P=0.003).Multivariate cox regression analysis indicated that systematic graded rewarming was a strong protective factor for survival time after trauma (HR=0.450, P=0.042).Further Logistic regression analysis for the occurrence of all-cause death in each time period showed that the OR of systematic graded rewarming pattern to all-cause death within 15 days and 30 days after trauma were 0.289 and 0.286,respectively,after adjusting the covariates(P=0.008,P=0.005).The temperature after rewarming for 2 h had a negative correlation with all-cause mortality within 30 days after trauma (OR=0.670, P=0.049). Conclusions Systematic graded rewarming is a protective factor for the survival time of patients with traumatic hypothermia and an independent factor affecting the risk of all-cause death within 15 days and 30 days after trauma.The temperature after rewarming for 2 h is expected to be an independent predictor of all-cause mortality of 30 days after trauma in the patients with hypothermia.The systematic graded rewarming pattern could reduce the mortality of hypothermic trauma patients.

Verification of Information Thermodynamics in a Trapped Ion System.

Information thermodynamics has developed rapidly over past years, and the trapped ions, as a controllable quantum system, have demonstrated feasibility to experimentally verify the theoretical predictions in the information thermodynamics. Here, we address some representative theories of information thermodynamics, such as the quantum Landauer principle, information equality based on the two-point measurement, information-theoretical bound of irreversibility, and speed limit restrained by the entropy production of system, and review their experimental demonstration in the trapped ion system. In these schemes, the typical physical processes, such as the entropy flow, energy transfer, and information flow, build the connection between thermodynamic processes and information variation. We then elucidate the concrete quantum control strategies to simulate these processes by using quantum operators and the decay paths in the trapped-ion system. Based on them, some significantly dynamical processes in the trapped ion system to realize the newly proposed information-thermodynamic models is reviewed. Although only some latest experimental results of information thermodynamics with a single trapped-ion quantum system are reviewed here, we expect to find more exploration in the future with more ions involved in the experimental systems.

[Effect of systematic graded rewarming measures on body temperature and prognosis of patients undergoing emergency trauma surgery].

OBJECTIVE: To observe the effect of systematic graded rewarming measures on body temperature and prognosis of patients with moderate and severe trauma [revised trauma score (RTS) < 12] requiring emergency operation. METHODS: A prospective randomized double-blind controlled study was conducted. From January 2020 to January 2021, 104 patients who underwent emergency trauma surgery in the Second Affiliated Hospital of Wenzhou Medical University were selected as the research object. According to random number table method, the patients were divided into traditional rewarming group and systematic graded rewarming group, with 52 cases in each group. Patients in traditional rewarming group (only record the body temperature without intervention, and start the rewarming process when the body temperature at any time was less than 36 centigrade); the patients in the system graded rewarming group start the preventive measures as soon as they were admitted to the hospital, and record the body temperature. When the body temperature at any time was less than 36 centigrade, start the graded rewarming process. Observe the rewarming effect, coagulation function, blood gas analysis and postoperative anesthesia recovery time of the two groups and final outcome. RESULTS: With the extension of time, the body temperature of the two groups increased gradually. The body temperature of the systematic grade rewarming group was significantly higher than that of the traditional rewarming group at 2 hours after rewarming and at discharge (centigrade: 36.23±0.77 vs. 35.84±0.93 at 2 hours after rewarming, 36.54±0.87 vs. 35.82±0.92 at discharge, both P < 0.05). The incidence of subsequent hypothermia was significantly lower than that in the traditional rewarming group [7.7% (4/52) vs. 25.0% (13/52), P < 0.05]. The postoperative activated partial thromboplastin time (APTT) of the two groups was significantly shorter than that at admission (s: 35.74±8.05 vs. 45.55±28.02 in the systematic rewarming group, P < 0.05; 38.35±6.48 vs. 42.40±13.18 in the traditional rewarming group, P < 0.05); the intraoperative and postoperative pH values in the systematic rewarming group were significantly higher than those at admission (7.33±0.05, 7.36±0.06 vs. 7.30±0.07, both P < 0.05), while there was no significant difference between the intraoperative and postoperative pH values in the traditional rewarming group and those at admission (7.31±0.06, 7.33±0.06 vs. 7.31±0.05, both P > 0.05). The postoperative prothrombin time (PT) and anesthesia recovery time in the systematic graded rewarming group were significantly shorter than those in the traditional rewarming group [PT (s): 15.05±2.44 vs. 17.94±3.48, anesthesia recovery time (hours): 14.40±11.76 vs. 17.35±10.51, all P < 0.05], and the pH value was significantly higher than that in the traditional rewarming group (7.36±0.06 vs. 7.33±0.06, P < 0.05). The systematic graded rewarming group had higher improvement rate and lower disability rate than the traditional rewarming group (76.9% vs. 65.4% and 17.3% vs. 25.0%, both P < 0.05). CONCLUSIONS: Systematic graded rewarming measures can improve the hypothermia of emergency trauma patients who received surgery, reduce the incidence of subsequent hypothermia of trauma patients, shorten the time of postoperative resuscitation, improve the coagulation function and blood gas indexes, improve the treatment rate, and reduce the incidence of disability.

Effect of Absorbent Foam Filling on Mechanical Behaviors of 3D-Printed Honeycombs.

Polylactic acid (PLA) hexagonal honeycomb structures were fabricated by using 3D-printing technology. By filling with absorbent polymethacrylimide (PMI) foam, a novel absorbent-foam-filled 3D-printed honeycomb was obtained. The in-plane (L- and W-direction) and out-of-plane (T-direction) compressive performances were studied experimentally and numerically. Due to absorbent PMI foam filling, the elastic modulus, compressive strength, energy absorption per unit volume, and energy absorption per unit mass of absorbent-foam-filled honeycomb under L-direction were increased by 296.34%, 168.75%, 505.57%, and 244.22%, respectively. Moreover, the elastic modulus, compressive strength, energy absorption per unit volume, and energy absorption per unit mass, under W-direction, also have increments of 211.65%, 179.85, 799.45%, and 413.02%, respectively. However, for out-of-plane compression, the compressive strength and energy absorption per unit volume were enhanced, but the density has also been increased; thus, it is not competitive in energy absorption per unit mass. Failure mechanism and dimension effects of absorbent-foam-filled honeycomb were also considered. The approach of absorbent foam filling made the 3D-printed honeycomb structure more competitive in electromagnetic wave stealth applications, while acting simultaneously as load-carrying structures.

Enhancement by Metallic Tube Filling of the Mechanical Properties of Electromagnetic Wave Absorbent Polymethacrylimide Foam.

By the addition of a carbon-based electromagnetic absorbing agent during the foaming process, a novel electromagnetic absorbent polymethacrylimide (PMI) foam was obtained. The proposed foam exhibits excellent electromagnetic wave-absorbing properties, with absorptivity exceeding 85% at a large frequency range of 4.9⁻18 GHz. However, its poor mechanical properties would limit its application in load-carrying structures. In the present study, a novel enhancement approach is proposed by inserting metallic tubes into pre-perforated holes of PMI foam blocks. The mechanical properties of the tube-enhanced PMI foams were studied experimentally under compressive loading conditions. The elastic modulus, compressive strength, energy absorption per unit volume, and energy absorption per unit mass were increased by 127.9%, 133.8%, 54.2%, and 46.4%, respectively, by the metallic tube filling, and the density increased only by 5.3%. The failure mechanism of the foams was also explored. We found that the weaker interfaces between the foam and the electromagnetic absorbing agent induced crack initiation and subsequent collapses, which destroyed the structural integrity. The excellent mechanical and electromagnetic absorbing properties make the novel structure much more competitive in electromagnetic wave stealth applications, while acting simultaneously as load-carrying structures.

Macroscopically distinct superposition in a spin ensemble coupled to superconducting flux-qubits.

Large optical nonlinearities can create fancy physics, such as big Schrödinger-cat states and quadrature squeezing. We present the possibility to practically generate macroscopic Schrödinger-cat states, based on a giant Kerr nonlinearity, in a diamond nitrogen-vacancy ensemble interacting with two coupled flux-qubits. The nonlinearity comes from a four-level N-type configuration formed by two coupled flux-qubits under the appropriately driving fields. We discuss the experimental feasibility in the presence of system dissipations using current laboratory technology and our scheme can be easily extended to other ensemble systems.

Catheter Aspiration With Recanalization for Budd-Chiari Syndrome With Inferior Vena Cava Thrombosis.

PURPOSE: To assess the safety and clinical effectiveness of catheter aspiration with recanalization in patients with Budd-Chiari syndrome (BCS) and inferior vena cava (IVC) thrombosis. MATERIALS AND METHODS: Between January 2010 and December 2017, 33 patients with BCS and IVC thrombosis were treated by catheter aspiration with IVC recanalization in our center. A 12 F angled-tip guiding catheter was used for the aspiration of thrombi in the IVC. Recanalization was conducted following thrombi aspiration. Rates of technical success, clinical success and long-term patency were calculated. RESULTS: Catheter aspiration with IVC recanalization was technically successful in all patients. After aspiration, no thrombi were detectable by IVC venography in 21 patients, while residual mural thrombi were found in 12 patients. IVC balloon dilation was performed in 18 patients, while stent insertion was performed in 15 patients. We also achieved clinical success in all patients. Symptomatic and asymptomatic pulmonary embolism were found in 1 patient each, respectively. The cumulative 1-, 3-, and 5-year patency rates were 93.6%, 93.6%, and 83.2%, respectively. All patients remained alive during the follow-up. CONCLUSIONS: Catheter aspiration with recanalization is a safe and efficacious approach to treating patients with BCS and IVC thrombosis.

Electromagnetic wave absorption and compressive behavior of a three-dimensional metamaterial absorber based on 3D printed honeycomb.

Lightweight structures with multi-functions such as electromagnetic wave absorption and excellent mechanical properties are required in spacecraft. A three-dimensional metamaterial absorber consisting of honeycomb and resistive films was proposed and fabricated through 3D printing and silk-screen printing technology. According to simulation and experiment results, the present three-dimensional metamaterial absorber can realize an absorptivity of more than 90% in a wide band of 3.53-24.00 GHz, and improve absorbing efficiency for transverse magnetic (TM) waves of oblique incidence angle from 0° to 70°. The compression test results reveal that compressive strength of the 3D printed honeycomb can reach 10.7 MPa with density of only 254.91 kg/m3, and the energy absorption per volume W v and per unit mass W m are 4.37 × 103 KJ/m3 and 17.14 KJ/Kg, respectively. The peak compressive strength and energy absorption per mass are at least 2.2 and 3 times comparing to metallic lattice cores with the same density. Outstanding electromagnetic wave absorption and mechanical performance make the present three-dimensional metamaterial absorber more competitive in engineering applications.

Anorectal functional outcome following laparoscopic low anterior resection for rectal cancer.

Low anterior resection (LAR) with total mesorectal excision has been considered a standard treatment for patients with rectal cancer. However, the functional outcome and life quality of laparoscopic LAR (LLAR) in Chinese patients remain unclear. A cohort of 51 Chinese patients (22 men and 29 women) who had undergone LLAR was included in this study. Anorectal manometry combined with the Wexner scores questionnaire were applied to assess functional outcome preoperatively (1 week) and postoperatively (at 3, 6 and 9 months). The validated Chinese versions of the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR38 questionnaires were also used to assess the patients' quality of life at the indicated time points. The results demonstrated that the manometric parameters exhibited a temporary decrease at 3 months postoperatively, but a gradual increase at 6 and 9 months, while the Wexner scores exhibited an opposite trend. Furthermore, patients with high anastomoses had significantly higher manometric parameters, a lower frequency of incontinence and lower Wexner scores compared with those with low anastomoses at 9 months (all P<0.05). For the entire cohort, quality of life at 3 months postoperatively was worse compared with the preoperative level, but returned to normal by 9 months. Patients with high anastomoses exhibited significantly better role, emotional and social function, had a better body image and sexual function, fewer problems with defecation and lower frequency of diarrhea, as well as fewer chemotherapy-related side effects at 6 months postoperatively when compared with the low anastomosis group (all P<0.05). In conclusion, LLAR is generally acceptable for Chinese patients with rectal cancer, particularly for those with middle or high rectal cancer, in terms of functional outcome and quality of life.

Self-forming TiBN Nanocomposite Multilayer Coating Prepared by Pulse Cathode Arc Method.

Novel multilayer structured TiBN coatings were deposited on Si (100) substrate using TiBN complex cathode plasma immersion ion implantation and deposition technique (PIIID). The coatings were characterized by X-ray diffraction (XRD), high-resolution transmission electron microcopy (HRTEM), energy-dispersive spectrometer (EDS) and ball-on-disk test. XRD results reveal that both samples of TiBN coatings have the main diffraction peak of TiN (200) and (220). Cross-section TEM images reveal that these coatings have the character of self-forming multilayer and consists of face-centered cubic TiN and hexagonal BN nanocrystalline embedded in amorphous matrix. Because of the existence of hexagonal BN, the friction coefficient of the new TiBN coating in room temperature is obviously lower than that of the monolithic TiN nanocrystalline coating.

High expression of Zinc-finger protein X-linked promotes tumor growth and predicts a poor outcome for stage II/III colorectal cancer patients.

Zinc-finger protein X-linked (ZFX) was recently identified as a novel oncoprotein in several human malignancies. In this study, we examined the correlation between ZFX expression and the clinical characteristics of stage II/III CRC patients, as well as the molecular mechanism by which ZFX apparently contributes to CRC tumor progression. Using immunohistochemistry, we detected expression of ZFX in CRC tissues collected from stage II/III patients and determined that its expression correlated with tumor differentiation and stage. Survival analysis indicated that patients with high ZFX expression had poorer overall and disease-free survival. ZFX knockdown in SW620 and SW480 CRC cells significantly inhibited cell proliferation and colony formation, enhanced apoptosis and induced cell cycle arrest. It also enhanced the sensitivity of CRC cells to 5-Fu. In a xenograft model, ZFX knockdown suppressed in vivo CRC tumor growth. Microarray analysis revealed the primary target of ZFX to be DUSP5. Whereas ZFX knockdown increased DUSP5 expression, DUSP5 knockdown rescued ZFX-mediated cell proliferation in ZFX knockdown cells. These findings demonstrate that ZFX promotes CRC progression by suppressing DUSP5 expression and suggest that ZFX is a novel prognostic biomarker and potentially useful therapeutic target in stage II/III CRC patients.

Verifying Heisenberg's error-disturbance relation using a single trapped ion.

Heisenberg's uncertainty relations have played an essential role in quantum physics since its very beginning. The uncertainty relations in the modern quantum formalism have become a fundamental limitation on the joint measurements of general quantum mechanical observables, going much beyond the original discussion of the trade-off between knowing a particle's position and momentum. Recently, the uncertainty relations have generated a considerable amount of lively debate as a result of the new inequalities proposed as extensions of the original uncertainty relations. We report an experimental test of one of the new Heisenberg's uncertainty relations using a single 40Ca+ ion trapped in a harmonic potential. By performing unitary operations under carrier transitions, we verify the uncertainty relation proposed by Busch, Lahti, and Werner (BLW) based on a general error-trade-off relation for joint measurements on two compatible observables. The positive operator-valued measure, required by the compatible observables, is constructed by single-qubit operations, and the lower bound of the uncertainty, as observed, is satisfied in a state-independent manner. Our results provide the first evidence confirming the BLW-formulated uncertainty at a single-spin level and will stimulate broad interests in various fields associated with quantum mechanics.

Discovery of a Novel Inhibitor of the Protein Tyrosine Phosphatase Shp2.

Shp2 is a ubiquitously expressed protein tyrosine phosphatase (PTP) related to adult acute myelogenous leukemia and human solid tumors. In this report, we describe identification of a potent Shp2 inhibitor, Fumosorinone (Fumos) from entomogenous fungi, which shows selective inhibition of Shp2 over other tested PTPs. Using a surface plasmon resonance analysis, we further confirmed the physical interaction between Shp2 and Fumos. Fumos inhibits Shp2-dependent activation of the Ras/ERK signal pathway downstream of EGFR, and interrupts EGF-induced Gab1-Shp2 association. As expected, Fumos shows little effects on the Shp2-independent ERK1/2 activation induced by PMA or oncogenic Ras. Furthermore, Fumos down-regulates Src activation, inhibits phosphorylation of Paxillin and prevents tumor cell invasion. These results suggest that Fumos can inhibit Shp2-dependent cell signaling in human cells and has a potential for treatment of Shp2-associated diseases.

Fast optical cooling of a nanomechanical cantilever by a dynamical Stark-shift gate.

The efficient cooling of nanomechanical resonators is essential to exploration of quantum properties of the macroscopic or mesoscopic systems. We propose such a laser-cooling scheme for a nanomechanical cantilever, which works even for the low-frequency mechanical mode and under weak cooling lasers. The cantilever is coupled by a diamond nitrogen-vacancy center under a strong magnetic field gradient and the cooling is assisted by a dynamical Stark-shift gate. Our scheme can effectively enhance the desired cooling efficiency by avoiding the off-resonant and undesired carrier transitions, and thereby cool the cantilever down to the vicinity of the vibrational ground state in a fast fashion.

High expression of Zinc-finger protein X-linked is associated with reduced E-cadherin expression and unfavorable prognosis in nasopharyngeal carcinoma.

Zinc-finger protein X-linked (ZFX), a novel transcription factor required for self-renewal of embryonic stem cells, has recently been implicated in the initiation and progression of various human malignancies. However, its clinical significance in cancer patients remains largely inconclusive and its role in nasopharyngeal carcinoma (NPC) has never been reported. In this study, quantitative real-time polymerase chain reaction, Western blot and Immunohistochemistry were performed to detect ZFX expression in NPC and normal nasopharyngeal tissues. As a result, we found ZFX expression was significantly elevated in NPC tissues compared with that in normal nasopharyngeal tissues. The statistical analysis based on immunohistochemical staining demonstrated that ZFX expression was significantly correlated with lymph node stage and clinical stage. Furthermore, we found NPC patients with high ZFX expression had lower 5-year overall survival rates, progression-free survival rates, loco-regional relapse-free survival rates and distant metastasis-free survival rates than those with low ZFX expression (all P<0.05). The multivariate analysis indicated that ZFX expression was an independent prognostic factor for patients with NPC. More importantly, we also detected E-cadherin expression in NPC tissues and found it was inversely correlated with ZFX expression in NPC tissues, suggesting a potential involvement of ZFX in Epithelial-mesenchymal transition (EMT). Therefore, it is speculated that ZFX may promote NPC progression partly by regulating EMT. In summary, our study not only for the first time identified that ZFX could serve as an effective prognostic biomarker for NPC patients, but also suggested that targeting ZFX might be a novel therapeutic strategy for preventing NPC progression and metastasis.

N-cadherin, a novel prognostic biomarker, drives malignant progression of colorectal cancer.

Recent studies have indicated that the epithelial-mesenchymal transition (EMT) is a key molecular mechanism involved in the development of colorectal cancer (CRC). N-cadherin is a mesenchymal marker of the EMT and has been closely linked to several human malignancies. However, its role in CRC has remained elusive. In the present study, qRT-PCR and western blot analysis indicated that N-cadherin expression was higher in tumor tissues than in that in their adjacent normal tissues. Immunohistochemical evaluation of N-cadherin and E-cadherin (an epithelial marker of the EMT), indicated that N-cadherin expression was significantly associated with tumor differentiation, tumor size as well as tumor, nodes and metastasis stage. Correlation analysis suggested the expression of N-cadherin was negatively correlated with that of E-cadherin in CRC tissues. Kaplan-Meier analysis indicated that patients with high N-cadherin expression had a significantly lower overall survival and disease-free survival rate than those with low N-cadherin expression, while the opposite was found for E-cadherin. Of note, the present study found that high N-cadherin expression was an independent prognostic factor for CRC. In vitro assays showed that N-cadherin was widely expressed in CRC cell lines and silencing of N-cadherin suppressed the proliferation and migration of the CRC cell line HT-29 by upregulating E-cadherin, suggesting a potential role of N-cadherin in inducing EMT. In conclusion, the present study suggested that N-cadherin has the potential of serving as a novel prognostic predictor and a promising therapeutic target for CRC.