The adapter protein FADD provides an alternate pathway for entry into the cell cycle by regulating APC/C-Cdh1 E3 ubiquitin ligase activity.

The E3 ubiquitin ligase APC/C-Cdh1 maintains the G0/G1 state, and its inactivation is required for cell cycle entry. We reveal a novel role for Fas-associated protein with death domain (FADD) in the cell cycle through its function as an inhibitor of APC/C-Cdh1. Using real-time, single-cell imaging of live cells combined with biochemical analysis, we demonstrate that APC/C-Cdh1 hyperactivity in FADD-deficient cells leads to a G1 arrest despite persistent mitogenic signaling through oncogenic EGFR/KRAS. We further show that FADDWT interacts with Cdh1, while a mutant lacking a consensus KEN-box motif (FADDKEN) fails to interact with Cdh1 and results in a G1 arrest due to its inability to inhibit APC/C-Cdh1. Additionally, enhanced expression of FADDWT but not FADDKEN, in cells arrested in G1 upon CDK4/6 inhibition, leads to APC/C-Cdh1 inactivation and entry into the cell cycle in the absence of retinoblastoma protein phosphorylation. FADD's function in the cell cycle requires its phosphorylation by CK1α at Ser-194 which promotes its nuclear translocation. Overall, FADD provides a CDK4/6-Rb-E2F-independent "bypass" mechanism for cell cycle entry and thus a therapeutic opportunity for CDK4/6 inhibitor resistance.

Comprehensive analysis of PHF5A as a potential prognostic biomarker and therapeutic target across cancers and in hepatocellular carcinoma.

OBJECTIVE: Cancer is a predominant cause of death globally. PHD-finger domain protein 5 A (PHF5A) has been reported to participate in various cancers; however, there has been no pan-cancer analysis of PHF5A. This study aims to present a novel prognostic biomarker and therapeutic target for cancer treatment. METHODS: This study explored PHF5A expression and its impact on prognosis, tumor mutation burden (TMB), microsatellite instability (MSI), functional status and tumor immunity across cancers using various public databases, and validated PHF5A expression and its correlation with survival, immune evasion, angiogenesis, and treatment response in hepatocellular carcinoma (HCC) using bioinformatics tools, qRT-PCR and immunohistochemistry (IHC). RESULTS: PHF5A was differentially expressed between tumor and corresponding normal tissues and was correlated with prognosis in diverse cancers. Its expression was also associated with TMB, MSI, functional status, tumor microenvironment, immune infiltration, immune checkpoint genes and tumor immune dysfunction and exclusion (TIDE) score in diverse malignancies. In HCC, PHF5A was confirmed to be upregulated by qRT-PCR and IHC, and elevated PHF5A expression may promote immune evasion and angiogenesis in HCC. Additionally, multiple canonical pathways were revealed to be involved in the biological activity of PHF5A in HCC. Moreover, immunotherapy and transcatheter arterial chemoembolization (TACE) worked better in the low PHF5A expression group, while sorafenib, chemotherapy and AKT inhibitor were more effective in the high expression group. CONCLUSIONS: This study provides a comprehensive understanding of the biological function of PHF5A in the carcinogenesis and progression of various cancers. PHF5A could serve as a tumor biomarker related to prognosis across cancers, especially HCC, and shed new light on the development of novel therapeutic targets.

Deep Learning Radiomics Model of Dynamic Contrast-Enhanced MRI for Evaluating Vessels Encapsulating Tumor Clusters and Prognosis in Hepatocellular Carcinoma.

BACKGROUND: Vessels encapsulating tumor cluster (VETC) is a critical prognostic factor and therapeutic predictor of hepatocellular carcinoma (HCC). However, noninvasive evaluation of VETC remains challenging. PURPOSE: To develop and validate a deep learning radiomic (DLR) model of dynamic contrast-enhanced MRI (DCE-MRI) for the preoperative discrimination of VETC and prognosis of HCC. STUDY TYPE: Retrospective. POPULATION: A total of 221 patients with histologically confirmed HCC and stratified this cohort into training set (n = 154) and time-independent validation set (n = 67). FIELD STRENGTH/SEQUENCE: A 1.5 T and 3.0 T; DCE imaging with T1-weighted three-dimensional fast spoiled gradient echo. ASSESSMENT: Histological specimens were used to evaluate VETC status. VETC+ cases had a visible pattern (≥5% tumor area), while cases without any pattern were VETC-. The regions of intratumor and peritumor were segmented manually in the arterial, portal-venous and delayed phase (AP, PP, and DP, respectively) of DCE-MRI and reproducibility of segmentation was evaluated. Deep neural network and machine learning (ML) classifiers (logistic regression, decision tree, random forest, SVM, KNN, and Bayes) were used to develop nine DLR, 54 ML and clinical-radiological (CR) models based on AP, PP, and DP of DCE-MRI for evaluating VETC status and association with recurrence. STATISTICAL TESTS: The Fleiss kappa, intraclass correlation coefficient, receiver operating characteristic curve, area under the curve (AUC), Delong test and Kaplan-Meier survival analysis. P value <0.05 was considered as statistical significance. RESULTS: Pathological VETC+ were confirmed in 68 patients (training set: 46, validation set: 22). In the validation set, DLR model based on peritumor PP (peri-PP) phase had the best performance (AUC: 0.844) in comparison to CR (AUC: 0.591) and ML (AUC: 0.672) models. Significant differences in recurrence rates between peri-PP DLR model-predicted VETC+ and VETC- status were found. DATA CONCLUSIONS: The DLR model provides a noninvasive method to discriminate VETC status and prognosis of HCC patients preoperatively. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.

Multitask deep learning for prediction of microvascular invasion and recurrence-free survival in hepatocellular carcinoma based on MRI images.

BACKGROUND AND AIMS: Accurate preoperative prediction of microvascular invasion (MVI) and recurrence-free survival (RFS) is vital for personalised hepatocellular carcinoma (HCC) management. We developed a multitask deep learning model to predict MVI and RFS using preoperative MRI scans. METHODS: Utilising a retrospective dataset of 725 HCC patients from seven institutions, we developed and validated a multitask deep learning model focused on predicting MVI and RFS. The model employs a transformer architecture to extract critical features from preoperative MRI scans. It was trained on a set of 234 patients and internally validated on a set of 58 patients. External validation was performed using three independent sets (n = 212, 111, 110). RESULTS: The multitask deep learning model yielded high MVI prediction accuracy, with AUC values of 0.918 for the training set and 0.800 for the internal test set. In external test sets, AUC values were 0.837, 0.815 and 0.800. Radiologists' sensitivity and inter-rater agreement for MVI prediction improved significantly when integrated with the model. For RFS, the model achieved C-index values of 0.763 in the training set and ranged between 0.628 and 0.728 in external test sets. Notably, PA-TACE improved RFS only in patients predicted to have high MVI risk and low survival scores (p < .001). CONCLUSIONS: Our deep learning model allows accurate MVI and survival prediction in HCC patients. Prospective studies are warranted to assess the clinical utility of this model in guiding personalised treatment in conjunction with clinical criteria.

Construction of a prediction model for postoperative prognosis in patients with resectable cholangiocarcinoma based on silence information regulator 2 expression. / æ²‰é»˜ä¿¡æ¯è°ƒèŠ‚å› å­2åœ¨èƒ†ç®¡ç™Œä¸­çš„è¡¨è¾¾åŠå ¶å¯¹å¯åˆ‡é™¤èƒ†ç®¡ç™Œæ‚£è€ é¢„åŽçš„é¢„æµ‹ä»·å€¼.

OBJECTIVES: To develop a prediction model for postoperative prognosis in patients with cholangiocarcinoma (CCA) based on the expression of silence information regulator 2 (SIRT2). METHODS: The differential expression of SIRT2 between CCA and normal tissues was analyzed using TCGA and GEO databases. Gene set enrichment analysis (GSEA) was used to explore potential mechanisms of SIRT2 in CCA. The expression of SIRT2 protein in CCA tissues and normal tissues (including 44 pairs of specimens) was also detected by immunohistochemistry (IHC) in 89 resectable CCA patients who underwent surgical treatment in the First Affiliated Hospital of Bengbu Medical College between January 2016 and December 2021. The relationship between SIRT2 expression and clinicopathological characteristics and prognosis of CCA patients was analyzed. A survival prediction model for patients with resectable CCA was constructed with COX regression results, the calibration curve and the time-dependent receiver operating characteristic curve (ROC) were used to evaluate the performance of the constructed model, and the predictive power between this model and the American Joint Committee on Cancer (AJCC)/TNM staging system (8th edition) was compared. RESULTS: SIRT2 mRNA was overexpressed in CCA tissues as shown in TCGA and GEO databases. IHC staining showed that SIRT2 protein expression in CCA tissues was significantly higher than that in adjacent non-tumor tissues. GSEA results showed that elevated SIRT2 expression may be involved in multiple metabolism-related signaling pathway, such as fatty acid metabolism, oxidative phosphorylation and amino acid metabolism. SIRT2 expression was related to serum triglycerides level, tumor size and lymph node metastasis (all P<0.05). The survival analysis results showed that patients with higher SIRT2 expression had a significantly lower overall survival (OS) than patients with lower SIRT2 expression (P<0.05). Univariate COX regression analysis suggested that pathological differentiation, clinical stage, postoperative treatment and SIRT2 expression level were associated with the prognosis of CCA patients (all P<0.05). Multivariate regression analysis confirmed that clinical stage and SIRT2 expression level were independent predictors of OS in postoperative CCA patients (both P<0.05). A nomogram based on SIRT2 for prediction of survival in postoperative CCA patients was constructed. The C-index of the model was 0.675, and the area under the time-dependent ROC curve (AUC) for predicting survival in the first, second, and third years was 0.879, 0.778, and 0.953, respectively, which were superior to those of AJCC/TNM staging system (8th Edition). CONCLUSIONS: SIRT2 is highly expressed in CCA tissues, which is associated with poor prognosis in patients with resectable CCA. The nomogram developed based on SIRT2 may have better predictive power than the AJCC/TNM staging system (8th edition) in prediction of survival of postoperative CCA patients.

[Methylselenocysteine Promotes Etoposide Cytotoxicity by Enhancing Homotypic Gap Junctions Composed of Connexin 26].

Objective: To investigate the effect of methylselenocysteine (MSC) on the function of homotypic gap junction (GJ) composed of connexin (Cx) 26 and its regulation of chemotherapeutic drug cytotoxicity. Methods: The Tet-on HeLa cells transfected with and stably expressing Cx26 were used as the tool cells. Effects of MSC on cell growth, GJ function, and Cx26 protein expression were examined by MTT method, parachute assay, and Western blot analysis, respectively. The cytotoxicity of chemotherapeutic drugs was determined by standard colony-forming assay, and the relationship between MSC's effect on cytotoxicity of these chemotherapeutic drugs and its regulation of GJ was further analyzed. Results: In Tet-on HeLa cells, doxycycline (Dox) can induce the expression of Cx26, which could then form functional GJs. Within a concentration range of 50 µmol/L, MSC had no significant effect on HeLa cell growth. Non-toxic concentrations of MSC can enhance GJs in a concentration-dependent manner and exert its effect at the nanomolar level. This effect was associated with an induction of Cx26 protein expression by MSC. Among the three common chemotherapeutic agents with different mechanisms of action, etoposide (Eto) presented cytotoxicity differences between HeLa cells cultured at low density (nonconfluent, no GJ formed) and high density (confluent, GJ formed). What's more, the inhibitory effect of Eto combined with MSC on HeLa cell colony formation was stronger than that of Eto alone, and this effect occurred only in HeLa cells with GJ formation. Conclusion: MSC can potentiate the cytotoxicity of Eto by enhancing the GJs composed of Cx26, indicating that combined strategy of selenide and chemotherapy shows potential value in the treatment of malignant tumors.

Venous gas caused by emphysematous pyelonephritis: a case report and review of literature.

BACKGROUND: Emphysematous pyelonephritis (EPN) is a potentially life-threatening disease caused by a gas-producing necrotizing bacterial infection that involves the renal parenchyma, collecting system, and/or perinephric tissue. EPN is often complicated by a previous diagnosis of diabetes mellitus, and venous air bubbles are an uncommon complication of it. We describe a 52-year-old woman who was admitted in coma, with a history of vomiting, and was found to have EPN with air bubbles in the uterine veins. We discuss the presentation, diagnosis, and pathogenesis of this uncommon but clinically significant event, and briefly review other case reports of venous gas or thrombosis caused by EPN. CASE PRESENTATION: We report the case of a 52-year-old woman with past history of type 2 diabetes mellitus, presenting with loss of consciousness after vomiting for half a day. Abdominal computed tomography scan revealed unilateral EPN with air bubbles in the uterine veins. The blood, pus, and urine cultures were positive for extended-spectrum beta-lactamase-producing Escherichia coli. The patient's condition improved well after conservative management comprising supportive measures, broad-spectrum antibiotics, percutaneous drainage therapy, and an open operation. CONCLUSIONS: Venous air bubbles are rare but fatal complication of EPN. Early diagnosis and treatment are critical to ensure good results.

Comprehensive analysis to identify pseudogenes/lncRNAs-hsa-miR-200b-3p-COL5A2 network as a prognostic biomarker in gastric cancer.

OBJECTIVE: Gastric cancer is one of the most common and deadly types of cancer. The molecular mechanism of gastric cancer progression remains unclear. MATERIALS AND METHODS: Four hub genes were identified through GEO and TCGA database screening and analysis. Prognostic analysis revealed that COL5A2 was the most likely to affect the prognosis of gastric cancer among the four hub genes. The relationships between COL5A2 and clinical variables and immune cell infiltration were analyzed. Then, COL5A2 was analyzed for single-gene differences and related functional enrichment. Using the starBase database for prediction and analysis, miRNAs and pseudogenes/lncRNAs that might combine with COL5A2 were identified; thus, the ceRNA network was constructed. Finally, the network was verified by Cox analysis and qPCR, and a nomogram was constructed. RESULTS: First, we found that COL5A2, COL12A1, BGN and THBS2 were highly expressed in gastric cancer. COL5A2 had statistical significance in overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) analysis. Immune infiltration analysis suggested that COL5A2 might influence the changes in the tumor immune microenvironment. The StarBase database was used to predict that 3 pseudogenes and 7 lncRNAs might inhibit the hsa-miR-200b-3p-COL5A2 axis in gastric cancer. The pseudogenes/lncRNA-hsa-miR-200b-3p-COL5A2 ceRNA network was identified and verified using Cox regression analysis and PCR. Finally, we constructed a nomogram. CONCLUSIONS: We elucidated the regulatory role of the pseudogenes/lncRNA-hsa-miR-200b-3p-COL5A2 network in gastric cancer progression and constructed a nomogram. These studies may provide effective treatments and potential prognostic biomarkers for gastric cancer.

The cytochrome P450 enzyme CYP24A1 increases proliferation of mutant KRAS-dependent lung adenocarcinoma independent of its catalytic activity.

We previously reported that overexpression of cytochrome P450 family 24 subfamily A member 1 (CYP24A1) increases lung cancer cell proliferation by activating RAS signaling and that CYP24A1 knockdown inhibits tumor growth. However, the mechanism of CYP24A1-mediated cancer cell proliferation remains unclear. Here, we conducted cell synchronization and biochemical experiments in lung adenocarcinoma cells, revealing a link between CYP24A1 and anaphase-promoting complex (APC), a key cell cycle regulator. We demonstrate that CYP24A1 expression is cell cycle-dependent; it was higher in the G2-M phase and diminished upon G1 entry. CYP24A1 has a functional destruction box (D-box) motif that allows binding with two APC adaptors, CDC20-homologue 1 (CDH1) and cell division cycle 20 (CDC20). Unlike other APC substrates, however, CYP24A1 acted as a pseudo-substrate, inhibiting CDH1 activity and promoting mitotic progression. Conversely, overexpression of a CYP24A1 D-box mutant compromised CDH1 binding, allowing CDH1 hyperactivation, thereby hastening degradation of its substrates cyclin B1 and CDC20, and accumulation of the CDC20 substrate p21, prolonging mitotic exit. These activities also occurred with a CYP24A1 isoform 2 lacking the catalytic cysteine (Cys-462), suggesting that CYP24A1's oncogenic potential is independent of its catalytic activity. CYP24A1 degradation reduced clonogenic survival of mutant KRAS-driven lung cancer cells, and calcitriol treatment increased CYP24A1 levels and tumor burden in Lsl-KRASG12D mice. These results disclose a catalytic activity-independent growth-promoting role of CYP24A1 in mutant KRAS-driven lung cancer. This suggests that CYP24A1 could be therapeutically targeted in lung cancers in which its expression is high.

No staghorn calculi and none/mild hydronephrosis may be risk factors for severe bleeding complications after percutaneous nephrolithotomy.

BACKGROUND: To explore the risk factors for severe bleeding complications after percutaneous nephrolithotomy (PCNL) according to the modified Clavien scoring system. METHODS: We retrospectively analysed 2981 patients who received percutaneous nephrolithotomies from January 2014 to December 2020. Study inclusion criteria were PCNL and postoperative mild or severe renal haemorrhage in accordance with the modified Clavien scoring system. Mild bleeding complications included Clavien 2, while severe bleeding complications were greater than Clavien 3a. It has a good prognosis and is more likely to be underestimated and ignored in retrospective studies in bleeding complications classified by Clavien 1, so no analysis about these was conducted in this study. Clinical features, medical comorbidities and perioperative characteristics were analysed. Chi-square, independent t tests, Pearson's correlation, Fisher exact tests, Mann-Whitney and multivariate logistic regression were used as appropriate. RESULTS: Of the 2981 patients 70 (2.3%), met study inclusion criteria, consisting of 51 men and 19 women, 48 patients had severe bleeding complications. The remaining 22 patients had mild bleeding. Patients with postoperative severe bleeding complications were more likely to have no or slight degree of hydronephrosis and have no staghorn calculi on univariate analysis (p < 0.05). Staghorn calculi (OR, 95% CI, p value 0.218, 0.068-0.700, 0.010) and hydronephrosis (OR, 95% CI, p value 0.271, 0.083-0.887, 0.031) were independent predictors for severe bleeding via multivariate logistic regression analysis. Other factors, such as history of PCNL, multiple kidney stones, site of puncture calyx and mean corrected intraoperative haemoglobin drop were not related to postoperative severe bleedings. CONCLUSIONS: The absence of staghorn calculi and a no or mild hydronephrosis were related to an increased risk of post-percutaneous nephrolithotomy severe bleeding complications.

LncRNA HOXD-AS1 promotes the metastasis of human hepatocellular carcinoma via modulating miR-326/SLC27A4.

BACKGROUND: Mounting evidences have indicated that long non-coding RNA (lncRNA) HOXD cluster antisense RNA 1 (HOXD-AS1) is dysregulated and participates into the progression of cancers. This study aims to investigate the biological roles and mechanisms of HOXD-AS1 in the metastasis of hepatocellular carcinoma (HCC). METHODS: The quantitative real-time PCR (qPCR) assay was used to assess the level of miR-326 and HOXD-AS1 in HCC tissues and cell lines. The growth of HCC cell was analyzed by using CCK-8 assay and colony formation assay. The migration and invasion of HCC cell were investigated by using wound healing and transwell invasion analysis. The expressions of SLC27A4, N-cadherin and E-cadherin were determined by western blotting. The growth of HCC cell in vivo was assessed by using xenograft model. RESULTS: Here, we elaborated that HOXD-AS1 was overexpressed in HCC tissues than that in the adjacent normal tissues and the level of HOXD-AS1 was related with the aggressive phenotypes of HCC. Functionally, downregulation of HOXD-AS1 repressed the proliferation, invasion abilities of HCC cell in vitro and the distant metastasis of HCC cell in vivo. Further investigations demonstrated that HOXD-AS1 directly bound with miR-326 and thereby regulated its endogenous target gene, solute carrier family 27 member 4 (SLC27A4). CONCLUSIONS: All these findings indicated that HOXD-AS1-miR-326-SLC27A4 axis participated into the progression of HCC.

Direct interactions of mitotic arrest deficient 1 (MAD1) domains with each other and MAD2 conformers are required for mitotic checkpoint signaling.

As a sensitive signaling system, the mitotic checkpoint ensures faithful chromosome segregation by delaying anaphase onset even when a single kinetochore is unattached to mitotic spindle microtubules. The key signal amplification reaction for the checkpoint is the conformational conversion of "open" mitotic arrest deficient 2 (O-MAD2) into "closed" MAD2 (C-MAD2). The reaction has been suggested to be catalyzed by an unusual catalyst, a MAD1:C-MAD2 tetramer, but how the catalysis is executed and regulated remains elusive. Here, we report that in addition to the well-characterized middle region of MAD1 containing the MAD2-interaction motif (MIM), both N- and C-terminal domains (NTD and CTD) of MAD1 also contribute to mitotic checkpoint signaling. Unlike the MIM, which stably associated only with C-MAD2, the NTD and CTD in MAD1 surprisingly bound both O- and C-MAD2, suggesting that these two domains interact with both substrates and products of the O-to-C conversion. MAD1NTD and MAD1CTD also interacted with each other and with the MPS1 protein kinase, which phosphorylated both NTD and CTD. This phosphorylation decreased the NTD:CTD interaction and also CTD's interaction with MPS1. Of note, mutating the phosphorylation sites in the MAD1CTD, including Thr-716, compromised MAD2 binding and the checkpoint responses. We further noted that Ser-610 and Tyr-634 also contribute to the mitotic checkpoint signaling. Our results have uncovered that the MAD1NTD and MAD1CTD directly interact with each other and with MAD2 conformers and are regulated by MPS1 kinase, providing critical insights into mitotic checkpoint signaling.

Polarization fading elimination for ultra-weak FBG array-based Φ-OTDR using a composite double probe pulse approach.

We proposed and experimentally demonstrated a technique using a composite-double-probe-pulse (CDPP) to eliminate the influence of polarization fading for Ultra-weak FBG (UWFBG) array-based phase-sensitive optical time-domain reflectometry (Φ-OTDR). The CDPP is composed of two optical pulses whose spatial interval is equal to twice the spatial interval of adjacent UWFBGs in the UWFBG array. The first optical pulse has a long duration, and the second one is composed of two continuous short pulses with orthogonal polarization states. The width of the short pulses is half of the long pulse, and their modulation frequencies are different from the long pulse. Using the proposed approach, we experimentally demonstrated that distributed quantitative measurements can be realized with high sensitivity based on only direct detection scheme, while the influence of polarization fading is effectively mitigated.

Integrated optofluidic micro-pumps in micro-channels with uniform excitation of a polarization rotating beam.

We report an integrated optofluidic micro-pump with a pair of mirrored stirrers of circulating micro-beads in a micro-channel, driven by plasmon-assisted optical manipulation with the excitation of a polarization rotating beam. H-shaped apertures (HSAs) on a gold surface produce strong near-field hot spots when they are illuminated with a light beam polarized parallel to the long axis of "H." With the rotating of excitation polarization, loops of HSAs with gradually varied orientations can produce the circulation of hot spots, which can further trap micro-beads and make them go around in circles. A different sequence of HSAs can produce a different direction and phase of bead rotation, even under uniform excitation. A pair of mirrored circulations of micro-beads in a micro-channel can induce very effective directional flow. Through numerical modeling, we find that a group of non-synchronized multi-phase mirrored circulations can produce a very uniform flow rate with a speed of more than 10 micrometers per second. These micro-pumps can be heavily integrated and activated by a single beam, while the flow direction of each pump can be regulated, even under a uniform excitation. Our design proposes a new approach for the flow pumping in micro- and nanofluidic devices.

Multi-level sorting of nanoparticles on multi-step optical waveguide splitter.

We propose an optofluidic sorting method for nanoparticles with different size by using optical waveguide splitter, and moreover, multiple cascaded splitters with different threshold could act as multi-level sorting unit. For a directional coupler (DC) with a specific wavelength excitation, the power splitting ratio is related to the coupling length and the gap between parallel waveguides. The power splitting ratio further determines the trapping force and potential wells distribution of both output ports. Most importantly, the potential well distribution is dependent on the particle size. For larger particles, the potential wells of both waveguides are inclined to merge, which makes it easier to be attracted and transfers to the adjacent waveguide with deeper potential well. The critical size of sorting is corresponding to the case when the barrier between wells just disappears, or the second derivative of the potential distribution is exactly zero. Moreover, since the sorting threshold of nanoparticles is related to coupling length and gap, multiple cascaded splitters with length or gap gradually varied could act as a multi-level sorting unit. A four-level sorting unit with a critical particle size of 600nm, 700nm, and 800nm are demonstrated. By considering the Brownian motion of particles and using particle-tracking method, the random distribution of nanoparticles on parallel waveguides in the sorting process is statistically presented, which agreed well with its corresponding potential wells distribution analysis. This sorting method based on multi-step optical waveguide splitter offers a number of advantages including single wavelength excitation, low loss, low power performance and ease of fabrication. This design can realize the high-throughput and large-scale nanoparticle automatic sorting in integrated photonic circuits, which have great potential for a large scale lab-on-a-chip system.

Two-dimensional arbitrary nano-manipulation on a plasmonic metasurface.

In this Letter, we report on a plasmonic nano-ellipse metasurface with the purpose of trapping and two-dimensional (2D) arbitrary transport of nanoparticles by means of rotating the polarization of an excitation beam. The locations of hot spots within a metasurface are polarization dependent, thus making it possible to turn on/off the adjacent hot spots and then convey the trapped target by rotating the incident polarization state. For the case of a metasurface with a unit cell of perpendicularly orientated nano-ellipses, the hot spots with higher intensities are located at both apexes of the nano-ellipse whose major axis is parallel to the direction of polarization. When the polarization gradually rotates to its counterpart direction, the trapped particle may move around the ellipse and transfer to the most adjacent ellipse, due to the unbalanced trap potentials around the nano-ellipse. Clockwise and counterclockwise rotation would guide the particle in a different direction, which makes it possible to convey the particle arbitrarily within the plasmonic metasurface by setting a time sequence of polarization rotation. As confirmed by the three-dimensional finite-difference time-domain analysis, our design offers a novel scheme of 2D arbitrary transport with nanometer accuracy, which could be used in many on-chip optofluidic applications.

Controllable trapping and releasing of nanoparticles by a standing wave on optical waveguides.

Based on the balance between the scattering force and the trapping force of an evanescent field of a standing wave on silicon waveguides, we propose a structure for controllable trapping and releasing of nanoparticles, which can act as pause operation for nanoparticle flow control. The design is realized by the cascade of an optical switch with a structure of a ring-assisted Mach-Zehnder interferometer (RAMZI) and a Sagnac loop reflector which connects to one output of the switch. Through thermal tuning, with a tiny refractive index change of 4.3×10-4 on a ring resonator, the output of a RAMZI can be switched between two ports. As for the release state of the nanoparticle flow, the light is guided to the port without a reflector. There is no standing wave or traps formed on a waveguide. Therefore, the scattering force dominates, which drives particles moving forward to output ports. Otherwise, for trapping a state, the light will be reflected by the Sagnac loop and form a stationary standing wave which provides an array of traps for nanoparticles. Most importantly, the structure can switch its state to trap or sequentially release particles without losing the control of samples which, to the best of our knowledge, has not been realized before. With the statistical description of particle motion, the balance between trapping and releasing is distinguished by the trapping time and tuned by reflectance. The feasibility of our design is verified using the three-dimensional finite-difference time domain and Maxwell stress tensor methods. Our structure possesses the merits of high compactness and time effectiveness and, thereby, it is highly suitable for on-chip optical manipulation of nanoparticle flow control, which brings great potential in integrated on-chip optofluidics.

Life-threatening hemorrhage from the corona mortis treated with balloon-assisted coiling technique.

Isolated pubic ramus fractures are common and generally uncomplicated injuries in the elderly. However, pubic ramus fractures are closely related to important vascular structures. The corona mortis, located in the retropubis, has an important anastomotic value, as it serves as a communication between the internal and external iliac vessels. The following case report describes an 88-year-old male who was diagnosed with a right superior pubic ramus fracture, which led to a severe picture of hemodynamic instability. Emergent angiography demonstrated injury of the corona mortis. After super-selective embolization of the corona mortis artery with a balloon-assisted coiling technique, the patient progressed satisfactorily and was discharged after 7days.

Performance Optimization for Phase-Sensitive OTDR Sensing System Based on Multi-Spatial Resolution Analysis.

This paper proposes and demonstrates a phase-sensitive optical time domain reflectometry (Φ-OTDR) sensing system with multi-spatial resolution (MSR) analysis property. With both theoretical analysis and an experiment, the qualitative relationship between spatial resolution (SR), signal-to-noise ratio (SNR) and the length of the vibration region has been revealed, which indicates that choosing a suitable SR to analyze the vibration event can effectively enhance the SNR of a sensing system. The proposed MSR sensing scheme offers a promising solution for the performance optimization of Φ-OTDR sensing systems, which can restore vibration events of different disturbance range with optimum SNR in merely a single measurement while maintaining the same detectable frequency range.

Delayed introduction of immunosuppressive regimens in critically ill patients after liver transplantation.

BACKGROUND: The manipulation of immunosuppression therapy remains challenging in patients who develop infectious diseases or multiple organ dysfunction after liver transplantation. We evaluated the outcomes of delayed introduction of immunosuppression in the patients after liver transplantation under immune monitoring with ImmuKnow assay. METHODS: From March 2009 to February 2014, 225 consecutive liver recipients in our institute were included. The delayed administration of immunosuppressive regimens was attempted in 11 liver recipients with multiple severe comorbidities. RESULTS: The median duration of non-immunosuppression was 12 days (range 5-58). Due to the infectious complications, the serial ImmuKnow assay showed a significantly low ATP level of 64±35 ng/mL in the early period after transplantation. With the development of comorbidities, the ImmuKnow value significantly increased. However, the acute allograft rejection developed when a continuous distinct elevation of both ATP and glutamyltranspeptidase levels was detected. The average ATP level measured just before the development of acute rejection was 271±115 ng/mL. CONCLUSIONS: The delayed introduction of immunosuppressive regimens is safe and effective in management of critically ill patients after liver transplantation. The serial ImmuKnow assay could provide a reliable depiction of the dynamics of functional immunity throughout the clinical course of a given patient.