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Background: The purpose of this study was to explore the impact of extreme precipitation on the risk of outpatient visits for depression and to further explore its associated disease burden and vulnerable population.Methods: A quasi-Poisson generalized linear regression model combined with distributed lag non-linear model (DLNM) was used to investigate the exposure-lag-response relationship between extreme precipitation (≥95th percentile) and depression outpatient visits from 2017 to 2019 in Suzhou city, Anhui Province, China.Results: Extreme precipitation was positively associated with the outpatient visits for depression. The effects of extreme precipitation on depression firstly appeared at lag4 [relative risk (RR): 1.047, 95% confidence interval (CI): 1.005-1.091] and lasted until lag7 (RR = 1.047, 95% CI: 1.009-1.087). Females, patients aged ≥65 years and patients with multiple outpatient visits appeared to be more sensitive to extreme precipitation. The attributable fraction (AF) and numbers (AN) of extreme precipitation on outpatient visits for depression were 5.00% (95% CI: 1.02-8.82%) and 1318.25, respectively.Conclusions: Our findings suggested that extreme precipitation may increase the risk of outpatient visits for depression. Further studies on the burden of depression found that females, aged ≥65 years, and patients with multiple visits were priority targets for future warnings. Active intervention measures against extreme precipitation events should be taken to reduce the risk of depression outpatient visits. [ABSTRACT FROM AUTHOR]

Neural rendering has garnered substantial attention owing to its capacity for creating realistic 3D scenes. However, its applicability to extensive scenes remains challenging, with limitations in effectiveness. In this work, we propose the Drone-NeRF framework to enhance the efficient reconstruction of unbounded large-scale scenes suited for drone oblique photography using Neural Radiance Fields (NeRF). Our approach involves dividing the scene into uniform sub-blocks based on camera position and depth visibility. Sub-scenes are trained in parallel using NeRF, then merged for a complete scene. We refine the model by optimizing camera poses and guiding NeRF with a uniform sampler. Integrating chosen samples enhances accuracy. A hash-coded fusion MLP accelerates density representation, yielding RGB and Depth outputs. Our framework accounts for sub-scene constraints, reduces parallel-training noise, handles shadow occlusion, and merges sub-regions for a polished rendering result. Moreover, our framework can be enhanced through the integration of semantic scene division, ensuring consistent allocation of identical objects to the same sub-block for improved object integrity and rendering performance. This Drone-NeRF framework demonstrates promising capabilities in addressing challenges related to scene complexity, rendering efficiency, and accuracy in drone-obtained imagery. • Propose a novel neural radiance fields framework for drone view reconstruction. • Parallel sub-block training achieves fast convergence and optimization. • Merge sub-blocks for large scenes and refine bounds to reduce edge shadows. • Semantic division assigns the same entities to sub-blocks for improved rendering. [ABSTRACT FROM AUTHOR]

At present, to evaluate the service life of space optical materials on the ground, 60Co γ-rays are usually used. However, the irradiation effect of the main space particles (protons, electrons) on materials is obviously different from that of γ-rays, which causes evaluation errors. In this study, the Monte Carlo method was used to study the transportation of 60Co γ-rays, protons, and electrons in the usually used optical materials, silica (SiO2). The number of secondary electrons produced by particles at different energies, and quantities in targets with different thicknesses was obtained, and the dominant effect (ionisation effect) of particles on silica was analysed. Based on the ionisation effect, using the number of secondary electrons as the equivalence parameter, the irradiation effect conversion relation of 60Co γ-rays and particles (protons and electrons) on silica was established, which satisfies Boltzmann's function. This work provides a new life evaluation method for 60Co γ-rays ground irradiation experiments. [ABSTRACT FROM AUTHOR]

• Micropatterned Cu surfaces with apparently improved LM wettability were obtained. • Low TIR was proved to demand low LM dosage meanwhile low trapped air area ratio. • Extra low, stable TIR of 0.37 m m 2 · K / W was attained on optimized surfaces. Thermal management systems are facing significant demand to dissipate increasing heat fluxes in time, however, heat transfer between solid surfaces is always obstructed due to the unperfect interfacial contact. Gallium-based room-temperature liquid metals (LM) are a type of emerging thermal interface materials (TIMs) with superior thermal conductivity and deformability, efficiently enhancing the through-interface thermal transfer. However, the poor wettability of LMs with engineering materials (e.g. , copper), which leads to non-negligible remaining gap/air at the interfaces, limits the further reduction of thermal interface resistance. Herein, a laser micropatterning approach is presented to significantly improve LM wetting behaviors with copper surfaces in the assistance of HCl solution, with the thermal interface resistance minimized to ∼0.37 mm2·K/W which is four orders of magnitudes lower than that of two bare surfaces directly contacted and a quarter of that of bare surfaces with LM as TIM. Micropatterns featuring dense, shallow and open channels were designed and demonstrated to effectively expel trapped air while using a small amount of LM, which were both found necessary for reducing thermal interface resistance. We believe this study can lay a foundation for the further development and practical application of LMs based thermal management strategies. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) circularized by back-splicing of pre-mRNA are widely expressed and affected the proliferation, invasion and metastasis of bladder cancer (BCa). However, the mechanism underlying circRNA biogenesis in mediating the distant metastasis of BCa still unexplored. Methods: RNA sequencing data between BCa and normal adjacent tissues was applied to identify the differentially expressed circRNAs. The functions of circNIPBL in BCa were investigated via a series of biochemical experiments. The Clinical significance of circNIPBL was examined in a cohort of larger BCa tissues. Results: In the present study, we identified a novel circRNA (hsa_circ_0001472), circNIPBL, which was significantly upregulated and had great influence on the poor prognosis of patients with BCa. Functionally, circNIPBL promotes BCa metastasis in vitro and in vivo. Mechanistically, circNIPBL upregulate the expression of Wnt5a and activated the Wnt/β-catenin signaling pathway via directly sponged miR-16-2-3p, leading to the upregulation of ZEB1, which triggers the EMT of BCa. Moreover, we revealed that ZEB1 interacted with the flanking introns of exons 2–9 on NIPBL pre-mRNA to trigger circNIPBL biogenesis, thus forming a positive feedback loop. Importantly, circNIPBL overexpression significantly facilitated the distant metastasis of BCa in the orthotopic bladder cancer model, while silencing ZEB1 remarkably blocked the effects of metastasis induced by circNIPBL overexpression. Conclusions: Our study highlights that circNIPBL-induced Wnt signaling pathway activation triggers ZEB1-mediated circNIPBL biogenesis, which forms a positive feedback loop via the circNIPBL/miR-16-2-3p/Wnt5a/ZEB1 axis, supporting circNIPBL as a novel therapeutic target and potential biomarker for BCa patients. [ABSTRACT FROM AUTHOR]

Hepatic ischemia-reperfusion injury (IRI) has been concerned as a main complication of liver surgery and transplantation. Previous studies show that reactive oxygen species (ROS) associated inflammation response and contribute to the liver damage during IRI. Coenzyme Q10 (CoQ10) has shown many beneficial effects on abrogating ROS production and ameliorating liver injury. This study found lower CoQ10 level in the process of liver IRI in a mouse model of hepatic IRI. Meanwhile, our results showed that CoQ10 administration significantly attenuate hepatic IRI proved by HE staining, serum ALT/AST. The NOD-like receptor protein 3 (NLRP3) inflammasome is activated by ROS which triggers the activation of inflammatory caspases. In this study, NLRP3 was significantly suppressed by CoQ10 while Foxp3 exhibited increased expression in liver. Furthermore, Kupffer cells (KCs) pretreated with CoQ10 under the condition of hypoxia and reoxygenation contributed to improved CD4+CD25+Foxp3+ regulatory T cells (Tregs) ratio in co-culture system. Furthermore, NLRP3 inflammasome activator treatment in vivo resulted in higher expression of caspase-1 and NLRP3 and reduction of Tregs in liver, which reversed the protection of CoQ10 in the liver injury. Taken together, our study discovered that CoQ10 can suppress NLRP3 activity in KCs and improves Foxp3+ Tregs differentiation depending on M2 macrophage polarization of KCs to ameliorate hepatic IRI. [Display omitted] • CoQ10 attenuated the hepatic ROS production and ischemia reperfusion injury. • CoQ10 suppressed NLRP3 inflammasome activation and promoted Tregs infiltration. • CoQ10 improved Foxp3 + Tregs differentiation depending on M2 macrophage polarization of KCs. [ABSTRACT FROM AUTHOR]

Embedded fiber optic sensors are considered a promising technology that can unlock the black box within a battery and understand the fundamental internal chemical and physical states during operation. However, the interfacial compatibility between the implanted fiber sensor and electrode materials has not yet been investigated. In this study, a fiber Bragg grating (FBG) sensor is incorporated into a solid-state lithium-metal coin cell at different interfaces to explore the resulting variations in electrochemical property. The presence of the fiber sensor accelerates the capacity fade compared with that of a pristine cell. To address this issue, a new method is employed to reduce the sensor diameter from 250 μm to 30 μm while preserving its sensing function. The reduction in the sensor diameter enhances its compatibility with the size of the electrode materials. Integrating a micro-FBG (MFBG) sensor into the solid-state cell also alleviates the defects related to interface stratification and void growth, leading to the improved capacity retention. Moreover, the feasibility of utilizing MFBG for in-situ monitoring of internal stress within a lithium-metal cell is demonstrated. This technique offers a scalable solution for the noninvasive monitoring of battery state, thereby improving the reliability and safety of cells. • Embedded optical fiber sensor affected solid-state lithium-metal cell performance. • Microfiber sensor improves the contact between embedded sensor and electrodes. • Operando monitoring of stress inside lithium-metal batteries by microfiber sensor. [ABSTRACT FROM AUTHOR]

Cancer-associated fibroblasts (CAFs) exhibit considerable heterogeneity in advanced cancers; however, the functional annotation and mechanism of CAFs in early-stage cancers remain elusive. Utilizing single-cell RNA sequencing and spatial transcriptomic, we identify a previously unknown PDGFRα+ITGA11+ CAF subset in early-stage bladder cancer (BCa). Multicenter clinical analysis of a 910-case cohort confirms that PDGFRα+ITGA11+ CAFs are associated with lymphovascular invasion (LVI) and poor prognosis in early-stage BCa. These CAFs facilitate LVI and lymph node (LN) metastasis in early-stage BCa, as evidenced in a PDGFRα+ITGA11+ CAFs-specific deficient mouse model. Mechanistically, PDGFRα+ITGA11+ CAFs promote lymphangiogenesis via recognizing ITGA11 surface receptor SELE on lymphatic endothelial cells to activate SRC-p-VEGFR3-MAPK pathway. Further, CHI3L1 from PDGFRα+ITGA11+ CAFs aligns the surrounding matrix to assist cancer cell intravasation, fostering early-stage BCa LVI and LN metastasis. Collectively, our study reveals the crucial role of PDGFRα+ITGA11+ CAFs in shaping metastatic landscape, informing the treatment of early-stage BCa LVI. [Display omitted] • A CAF subset that expresses PDGFRα and ITGA11 is identified in early-stage BCa • PDGFRα+ITGA11+ CAFs enhance lymphangiogenesis via ITGA11-SELE interplay • PDGFRα+ITGA11+ CAFs align ECM via CHI3L1 to assist BCa cell intravasation • Targeting PDGFRα+ITGA11+ CAFs inhibits LVI and LN metastasis of early-stage BCa Zheng et al. uncover the cellular landscape in early-stage BCa and report a CAF subset characterized by PDGFRα and ITGA11. They demonstrate that PDGFRα+ITGA11+ CAFs stimulate lymphangiogenesis and align ECM to assist BCa cell intravasation, facilitating the LVI and LN metastasis of early-stage BCa, which provides a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Small ubiquitin-like modifier (SUMO) binding (termed SUMOylation) emerged as the inducer for the sorting of bioactive molecules into extracellular vesicles (EVs), triggering lymphangiogenesis and further driving tumor lymph node (LN) metastasis, but the precise mechanisms remain largely unclear. Here, we show that bladder cancer (BCa) cell-secreted EVs mediated intercellular communication with human lymphatic endothelial cells (HLECs) through transmission of the long noncoding RNA ELNAT1 and promoted lymphangiogenesis and LN metastasis in a SUMOylation-dependent manner in both cultured BCa cell lines and mouse models. Mechanistically, ELNAT1 induced UBC9 overexpression to catalyze the SUMOylation of hnRNPA1 at the lysine 113 residue, which mediated recognition of ELNAT1 by the endosomal sorting complex required for transport (ESCRT) and facilitated its packaging into EVs. EV-mediated ELNAT1 was specifically transmitted into HLECs and epigenetically activated SOX18 transcription to induce lymphangiogenesis. Importantly, blocking the SUMOylation of tumor cells by downregulating UBC9 expression markedly reduced lymphatic metastasis in EV-mediated, ELNAT1-treated BCa in vivo. Clinically, EV-mediated ELNAT1 was correlated with LN metastasis and a poor prognosis for patients with BCa. These findings highlight a molecular mechanism whereby the EV-mediated ELNAT1/UBC9/SOX18 regulatory axis promotes lymphangiogenesis and LN metastasis in BCa in a SUMOylation-dependent manner and implicate ELNAT1 as an attractive therapeutic target for LN metastatic BCa. [ABSTRACT FROM AUTHOR]

Patients with bladder cancer (BCa) with clinical lymph node (LN) metastasis have an extremely poor prognosis. VEGF-C has been demonstrated to play vital roles in LN metastasis in BCa. However, approximately 20% of BCa with LN metastasis exhibits low VEGF-C expression, suggesting a VEGF-C-independent mechanism for LN metastasis of BCa. Herein, we demonstrate that BCa cell-secreted exosome-mediated lymphangiogenesis promoted LN metastasis in BCa in a VEGF-C-independent manner. We identified an exosomal long noncoding RNA (lncRNA), termed lymph node metastasis-associated transcript 2 (LNMAT2), that stimulated human lymphatic endothelial cell (HLEC) tube formation and migration in vitro and enhanced tumor lymphangiogenesis and LN metastasis in vivo. Mechanistically, LNMAT2 was loaded to BCa cell-secreted exosomes by directly interacting with heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1). Subsequently, exosomal LNMAT2 was internalized by HLECs and epigenetically upregulated prospero homeobox 1 (PROX1) expression by recruitment of hnRNPA2B1 and increasing the H3K4 trimethylation level in the PROX1 promoter, ultimately resulting in lymphangiogenesis and lymphatic metastasis. Therefore, our findings highlight a VEGF-C-independent mechanism of exosomal lncRNA-mediated LN metastasis and identify LNMAT2 as a therapeutic target for LN metastasis in BCa. [ABSTRACT FROM AUTHOR]

• Ice-pinning mechanism on superhydrophobic surfaces was revealed. • Anti-ice-pinning strategies were proposed for obtaining robust icephobicity considering structural design. • Anti-ice-pinning superhydrophobic surfaces were developed by ultrafast laser. • The surface showed excellent static anti-icing performances (<0.1 kPa after 1st deicing cycle). • The developed materials can be used for passive anti-icing under static freezing conditions. Micro-nanostructured superhydrophobic surfaces (SHSs) are considered a promising industrial solution to catastrophic ice accretion, e.g., in aviation and powerlines. However, high ice-adhesion strength causes poor icephobicity on SHSs once ice embeds into the valleys among micro-nanostructures, particularly under low-temperature and high-humidity circumstances. Retarding ice-pinning is the key to realizing robust icephobicity, which needs to be made by customizable structures on SHSs. In this study, ice-pinning was identified to occur through liquid penetration, condensation, icing, and frost-filling processes. The ultimate state ice enlarged the grabbing-structure area, directly leading to a high ice adhesion. Specifically, we designed anti-ice-pinning structures comprising micro-scale features, concave sidewalls and heterogenous depths, and nano-scale particles, which were manufactured by an ultrafast laser. The developed anti-ice-pinning SHSs elevate static anti-icing function by the extremely low ice-adhesion strengths (<0.1 kPa after 1st deicing cycle and ∼ 10 kPa after the 30th deicing cycle at an ambient temperature of −20 ℃ and relative humidity of 18 %) and ice-structure interfacial morphologies captured by cryo-SEM. This previously unknown use of anti-ice-pinning strategies and engineering materials to enhance the robust icephobicity contributes to excellent control over ice adhesion. [ABSTRACT FROM AUTHOR]

[Display omitted] • Fabricated an environmentally adapted slippery-superhydrophobic switchable surface. • The constructed surfaces spontaneously adapted to various icing environments. • The constructed surfaces combined anti-ice-pinning and anti-water-pressure properties with durable switchability. • The surface is facilely and large-scale fabricated, showing great potential for practical applications. Numerous state-of-the-art anti-icing surfaces have been developed to avoid undesired icing. However, they generally only work in the single static icing occasion. Under dynamic disturbances, the unstable interfacial states could fail easily, leading to the loss of icephobicity. The impalement of air interfaces on superhydrophobic surfaces and liquids captured by lubricant interfaces are two most known failure mechanisms. How to address these problems and develop a surface with adaptability to changeable harsh environments is of great challenge but of high value. Here we analyze the effects of structural sizes on surface resistance forces and slippery durability and propose a structural design method to balance their relationship. Adopting the optimized structures, we fabricate an environmentally adapted slippery-superhydrophobic switchable surface, which reversibly switches interface states to maintain low adhesion in different environments. We demonstrate that the surfaces show excellent slippery anti-icing properties in static environments and overcome impalement issues. Even in extreme low-temperature environments, a photothermal-assisted droplet self-dislodging is realized. Confronting dynamic disturbances, the superhydrophobic interfaces are spontaneously activated with the broadened anti-water-impact ability (up to 200 kPa). A series of experiments confirm the long-term anti-icing, switchability and universality of our constructed surfaces, which could accelerate practical anti-icing applications in many related fields. [ABSTRACT FROM AUTHOR]

• Integrating static and ultrasonic structural health monitoring. • Combination of FBG strain arrays and PSFBG acoustic emission sensors. • Structural health monitoring of full-size aerospace multi-function capsule. • Alerting the unhealthy status of aerospace structures before catastrophic failure. In this study, we developed an integrated static and ultrasonic structural health monitoring (SHM), that was achieved using fiber Bragg grating (FBG) arrays and phase-shifted FBG (PSFBG) sensors, to monitor a full-size aerospace multi-function capsule under varying load. The FBG and PSFBG were bonded using direct and remote adhesive methods, respectively, to ensure the performance of the integrated SHM. The static strain measured by FBG accurately followed the loading curve during the initial 15 min of the test, and subsequently exhibited an irregular trend due to damage. Acoustic emission signals induced by damage were first detected by PSFBG at 15 min 11 sec. Following the detectable irregular strain and AE signals, the failure of the capsule manifested as a wrinkling ultimately occurred at 18 min. The FBG arrays and PSFBG sensors performed well for the integrated SHM and demonstrated that the newly proposed method can alert the unhealthy status of a large-scale aerospace structure before catastrophic failure. [ABSTRACT FROM AUTHOR]

• We developed a chemical-free ultrathin aluminum wick with dual-scale microgrooves. • The wick exhibited an improved K/R eff about 1.322 µm with a depth of about 100 µm. • The enhanced capillary performance was related to the interaction of liquid in each groove. • This wick kept the ability to transport liquid under bending angles of 90 and 135°. With the burgeoning development of electronic devices with higher heat flux, thinner volume, lighter weight, and flexibility, heat pipes and vapor chambers are facing big challenges, especially in fabricating high-performance wicks within limited space. Microgrooves have gained increasing interest for the ability to be directly curved on the substrates, whereas the capillary performance enhancement hits a bottleneck. In this study, a chemical-free ultrathin aluminum wick with dual-scale microgrooves was fabricated via two-step laser texturing in 0.3 mm thick AA6061. The resultant surface, composed of main microgrooves and periodic sub-microgrooves in the ridges and valleys, demonstrated enhanced capillary performance via capillary rise rate experiments. The interaction of liquids in dual-scale microgrooves, that was the pumping effect and the flow resistance reducing effect, would be the main reason for the capillary performance enhancement. The ultrathin aluminum wick with dual-scale microgrooves exhibited a K / R eff about 1.322 µm with a shallow depth of about 100 µm, increased by 11.3% compared with that of single-scale microgrooves due to the assistance of the sub-microgrooves. This wick kept the ability to transport liquid under bending angles of 90 and 135°. Moreover, the wicking performance of different liquids decreased with the decrease of surface tension to viscosity ratio. The ultrathin aluminum wick with dual-scale microgrooves showed enhanced capillary performance, which was among the best with thickness less than 200 µm to our knowledge. This work provides insight into the design of high-performance wicks within limited space and weight. [ABSTRACT FROM AUTHOR]

The space–time asymptotic expansion method is investigated to reveal the multiscale transient thermal conduction in the periodic composite structures with temperature-dependent thermal properties. [Display omitted] Space-time asymptotic expansion method (AEM) is a rigorous method for solving the multiscale transient thermal conduction problem in periodic composites. However, the AEM is still difficult to model the thermal behavior in composites when temperature-dependent material properties are taken into account. Besides, its complex and costly implementation also restricts the usage of AEM. A space–time AEM for multiscale transient thermal analysis is comprehensively studied in this study to address these issues properly. After the constitutive equation of temperature-dependent characteristic temperature tensor and effective thermal properties in the transient thermal conduction is deduced from the solid theoretical base, a new implementation approach comprised of both homogenization and localization is developed. It can directly model the characteristic temperature tensor within a representative volume element model under simple periodic boundary conditions and linear temperature loads, differing from conventional AEM, which requires complex location-related heat flux loads. Moreover, a new characteristic heat flux tensor is proposed to replace the characteristic temperature tensor in the localization of heat flux. All these contributions simplify the localization in the new implementation. The thermal behavior of A fiber-reinforced composite during the forming process is investigated using the space–time AEM and multiscale finite element method. The comparison results between space–time AEM and multiscale finite element method indicate that the space–time AEM is accurate and efficient as the differences of local temperature and heat flux are 0.0051 °C and 7.2 × 10-5 W/mm2, and the total nodes in space–time AEM is only about half of the multiscale finite element method. [ABSTRACT FROM AUTHOR]

Heterogeneous extracellular vesicles (EVs) from various types of tumours are acknowledged for inducing the formation of pre-metastatic "niches" in draining lymph nodes (LNs) to promote lymphatic metastasis. In order to identify the specific subpopulations of EVs involved, we performed high-resolution proteomic analysis combined with nanoflow cytometry of bladder cancer (BCa) tissue-derived EVs to identify a novel subset of tumour-derived EVs that contain integrin α6 (ITGA6 + EVs) and revealed the positive correlation of ITGA6 + EVs with the formation of pre-metastatic niche in draining LNs and lymphatic metastasis in multicentre clinical analysis of 820-case BCa patients. BCa-derived ITGA6 + EVs induced E-selectin (SELE)-marked lymphatic remodelling pre-metastatic niche and promoted metastasis in draining LNs through delivering cargo circRNA-LIPAR to lymphatic endothelial cells in vivo and in vitro. Mechanistically, LIPAR linked ITGA6 to the switch II domain of RAB5A and sustained RAB5A GTP-bound activated state, thus maintaining the production of ITGA6 + EVs loaded with LIPAR through endosomal trafficking. ITGA6 + EVs targeted lymphatic vessels through ITGA6-CD151 interplay and released LIPAR to induce SELE overexpression-marked lymphatic remodelling pre-metastatic niche. Importantly, we constructed engineered-ITGA6 EVs to inhibit lymphatic pre-metastatic niche, which suppressed lymphatic metastasis and prolonged survival in preclinical models. Collectively, our study uncovers the mechanism of BCa-derived ITGA6 + EVs mediating pre-metastatic niche and provides an engineered-EV-based strategy against BCa lymphatic metastasis., (© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Ubiquitination plays an essential role in protein stability, subcellular localization, and interactions. Crosstalk between different types of ubiquitination results in distinct biological outcomes for proteins. However, the role of ubiquitination-related crosstalk in lymph node (LN) metastasis and the key regulatory factors controlling this process have not been determined. Using high-throughput sequencing, we found that ubiquitin-conjugating enzyme E2 C (UBE2C) was overexpressed in bladder cancer (BCa) and was strongly associated with an unfavorable prognosis. Overexpression of UBE2C increased BCa lymphangiogenesis and promoted LN metastasis both in vitro and in vivo. Mechanistically, UBE2C mediated sodium-coupled neutral amino acid transporter 2 (SNAT2) monoubiquitination at lysine 59 to inhibit K63-linked polyubiquitination at lysine 33 of SNAT2. Crosstalk between monoubiquitination and K63-linked polyubiquitination increased SNAT2 membrane protein levels by suppressing epsin 1-mediated (EPN1-mediated) endocytosis. SNAT2 facilitated glutamine uptake and metabolism to promote VEGFC secretion, ultimately leading to lymphangiogenesis and LN metastasis in patients with BCa. Importantly, inhibition of UBE2C significantly attenuated BCa lymphangiogenesis in a patient-derived xenograft model. Our results reveal the mechanism by which UBE2C mediates crosstalk between the monoubiquitination and K63-linked polyubiquitination of SNAT2 to promote BCa metastasis and identify UBE2C as a promising target for treating LN-metastatic BCa.

Competing Interests: The authors declare no competing interests.

Aberrant gene expression is a prominent feature of metastatic cancer. Translational initiation is a vital step in fine-tuning gene expression. Thus, exploring translation initiation regulators may identify therapeutic targets for preventing and treating metastasis. Herein, we identified that DHCR24 was overexpressed in lymph node (LN) metastatic bladder cancer and correlated with poor prognosis of patients. DHCR24 promoted lymphangiogenesis and LN metastasis of bladder cancer in vitro and in vivo. Mechanistically, DHCR24 mediated and recognized the SUMO2 modification at lysine 108 of hnRNPA2B1 to foster TBK1 mRNA circularization and eIF4F initiation complex assembly by enhancing hnRNPA2B1-eIF4G1 interaction. Moreover, DHCR24 directly anchored to TBK1 mRNA 3'-untranslated region to increase its stability, thus forming a feed forward loop to elevate TBK1 expression. TBK1 activated PI3K/Akt signaling to promote VEGFC secretion, resulting in lymphangiogenesis and LN metastasis. DHCR24 silencing significantly impeded bladder cancer lymphangiogenesis and lymphatic metastasis in a patient-derived xenograft model. Collectively, these findings elucidate DHCR24-mediated translation machinery that promotes lymphatic metastasis of bladder cancer and supports the potential application of DHCR24-targeted therapy for LN-metastatic bladder cancer., Significance: DHCR24 is a SUMOylation regulator that controls translation initiation complex assembly and orchestrates TBK1 mRNA circularization to activate Akt/VEGFC signaling, which stimulates lymphangiogenesis and promotes lymph node metastasis in bladder cancer., (©2023 The Authors; Published by the American Association for Cancer Research.)

Objective . The OSort algorithm, a pivotal unsupervised spike sorting method, has been implemented in dedicated hardware devices for real-time spike sorting. However, due to the inherent complexity of neural recording environments, OSort still grapples with numerous transient cluster occurrences during the practical sorting process. This leads to substantial memory usage, heavy computational load, and complex hardware architectures, especially in noisy recordings and multi-channel systems. Approach . This study introduces an optimized OSort algorithm (opt-OSort) which utilizes correlation coefficient ( CC ), instead of Euclidean distance as classification criterion. The CC method not only bolsters the robustness of spike classification amidst the diverse and ever-changing conditions of physiological and recording noise environments, but also can finish the entire sorting procedure within a fixed number of cluster slots, thus preventing a large number of transient clusters. Moreover, the opt-OSort incorporates two configurable validation loops to efficiently reject cluster outliers and track recording variations caused by electrode drifting in real-time. Main results . The opt-OSort significantly reduces transient cluster occurrences by two orders of magnitude and decreases memory usage by 2.5-80 times in the number of pre-allocated transient clusters compared with other hardware implementations of OSort. The opt-OSort maintains an accuracy comparable to offline OSort and other commonly-used algorithms, with a sorting time of 0.68 µ s as measured by the hardware-implemented system in both simulated datasets and experimental data. The opt-OSort's ability to handle variations in neural activity caused by electrode drifting is also demonstrated. Significance . These results present a rapid, precise, and robust spike sorting solution suitable for integration into low-power, portable, closed-loop neural control systems and brain-computer interfaces., (Creative Commons Attribution license.)

Lymph node (LN) metastasis is one of the predominant metastatic routes of non-small cell lung cancer (NSCLC) and is considered as a leading cause for the unsatisfactory prognosis of patients. Although lymphangiogenesis is well-recognized as a crucial process in mediating LN metastasis, the regulatory mechanism involving lymphangiogenesis and LN metastasis in NSCLC remains unclear. In this study, we employed high-throughput sequencing to identify a novel circular RNA (circRNA), circTLCD4-RWDD3, which was significantly upregulated in extracellular vesicles (EVs) from LN metastatic NSCLC and was positively associated with deteriorated OS and DFS of patients with NSCLC from multicenter clinical cohort. Downregulating the expression of EV-packaged circTLCD4-RWDD3 inhibited lymphangiogenesis and LN metastasis of NSCLC both in vitro and in vivo. Mechanically, circTLCD4-RWDD3 physically interacted with hnRNPA2B1 and mediated the SUMO2 modification at K108 residue of hnRNPA2B1 by upregulating UBC9. Subsequently, circTLCD4-RWDD3-induced SUMOylated hnRNPA2B1 was recognized by the SUMO interaction motif (SIM) of ALIX and activated ALIX to recruit ESCRT-III, thereby facilitating the sorting of circTLCD4-RWDD3 into NSCLC cell-derived EVs. Moreover, EV-packaged circTLCD4-RWDD3 was internalized by lymphatic endothelial cells to activate the transcription of PROX1, resulting in the lymphangiogenesis and LN metastasis of NSCLC. Importantly, blocking EV-mediated transmission of circTLCD4-RWDD3 via mutating SIM in ALIX or K108 residue of hnRNPA2B1 inhibited the lymphangiogenesis and LN metastasis of NSCLC in vivo. Our findings reveal a precise mechanism underlying SUMOylated hnRNPA2B1-induced EV packaging of circTLCD4-RWDD3 in facilitating LN metastasis of NSCLC, suggesting that EV-packaged circTLCD4-RWDD3 could be a potential therapeutic target against LN metastatic NSCLC., (© 2023. The Author(s).)

Objective: Excessive daytime sleepiness (EDS) and insomnia symptoms are common in patients with major depressive disorder (MDD), which might lead to a poor prognosis and an increased risk of depression relapse. The current study aimed to investigate the prevalence, and sociodemographic and clinical correlates of EDS and insomnia symptoms among adolescents with MDD., Methods: The sample of this cross-sectional study included 297 adolescents (mean age=15.26 years; range=12-18 years; 218 females) with MDD recruited from three general and four psychiatric hospitals in five cities (Hefei, Bengbu, Fuyang, Suzhou, and Ma'anshan) in Anhui Province, China between January and August, 2021. EDS and insomnia symptoms, and clinical severity of depressive symptoms were assessed using Epworth sleepiness scale, Insomnia Severity Index, and Clinical Global Impression-Severity., Results: The prevalence of EDS and insomnia symptoms in adolescents with MDD was 39.7% and 38.0%, respectively. Binary logistic regression analyses showed that EDS symptoms were significantly associated with higher body mass index (odds ratio [OR]=1.097, 95% confidence interval [CI]=1.027-1.172), more severe depressive symptoms (OR=1.313, 95% CI=1.028-1.679), and selective serotonin reuptake inhibitors use (OR=2.078, 95% CI=1.199-3.601). And insomnia symptoms were positively associated with female sex (OR=1.955, 95% CI=1.052-3.633), suicide attempts (OR=1.765, 95% CI=1.037-3.005), more severe depressive symptoms (OR=2.031, 95% CI=1.523-2.709), and negatively associated with antipsychotics use (OR=0.433, 95% CI=0.196-0.952)., Conclusion: EDS and insomnia symptoms are common among adolescents with MDD. Considering their negative effects on the clinical prognosis, regular screening and clinical managements should be developed for this patient population.

Deep-learning-based localization and mapping approaches have recently emerged as a new research direction and receive significant attention from both industry and academia. Instead of creating hand-designed algorithms based on physical models or geometric theories, deep learning solutions provide an alternative to solve the problem in a data-driven way. Benefiting from the ever-increasing volumes of data and computational power on devices, these learning methods are fast evolving into a new area that shows potential to track self-motion and estimate environmental models accurately and robustly for mobile agents. In this work, we provide a comprehensive survey and propose a taxonomy for the localization and mapping methods using deep learning. This survey aims to discuss two basic questions: whether deep learning is promising for localization and mapping, and how deep learning should be applied to solve this problem. To this end, a series of localization and mapping topics are investigated, from the learning-based visual odometry and global relocalization to mapping, and simultaneous localization and mapping (SLAM). It is our hope that this survey organically weaves together the recent works in this vein from robotics, computer vision, and machine learning communities and serves as a guideline for future researchers to apply deep learning to tackle the problem of visual localization and mapping.

Previous epidemiological studies have reported seasonal variation patterns of depression symptoms, which may be influenced by bad weather conditions, such as a lack of sunlight. However, evidence on the acute effects of sunshine duration on outpatient visits for depression is limited, especially in developing countries, and the results are inconsistent. We collected daily outpatient visits for depression from the local mental health centre in Suzhou, Anhui Province, China, during 2017-2019. We defined the 5th and 95th sunshine percentiles as short and long sunshine durations, respectively. A quasi-Poisson generalized linear regression model combined with a distributed lag nonlinear model was used to quantitatively assess the effects of short and long sunshine durations on outpatient visits for depression. Stratified analyses were further performed by gender, age and number of visits to identify vulnerable populations. A total of 26,343 depression cases were collected during the study period. An approximate U-shaped exposure-response association was observed between sunshine duration and depression outpatient visits. The cumulative estimated relative risks (RRs) for short and long sunshine durations at lag 0-21 days were 1.53 [95% confidence intervals (CI): 1.14, 2.06] and 1.13 (95% CI: 0.88, 1.44), respectively. Moreover, a short sunshine duration was associated with a greater disease burden than a long sunshine duration, with attributable fractions (AFs) of 16.64% (95% CI: 7.8%, 23.89%) and 2.24% (95% CI: -2.65%, 5.74%), respectively. Subgroup analysis showed that males, people aged less than 45 years and first-visit cases may be more susceptible to a lack of sunlight. For a long sunshine duration, no statistically significant associations were found in any population groups. Our study found that a short sunshine duration was associated with an increased risk of depression. The government, medical institutions, family members and patients themselves should fully recognize the important role of sunlight and take active measures to prevent depression., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: There remains uncertainty regarding the differences in patient outcomes between monopolar transurethral resection of the prostate (MTURP) and bipolar TURP (BTURP) in the management of lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO)., Methods: A systematic literature search was carried out up to March 19, 2019. Methods in the Cochrane Handbook were followed. Certainty of evidence (CoE) was assessed using the GRADE approach., Results: A total of 59 randomized controlled trials (RCTs) with 8924 participants were included. BTURP probably results in little to no difference in International Prostate Symptom Score (IPSS) at 12 months (mean difference -0.24, 95% confidence internal [CI] -0.39--0.09; participants=2531; RCTs=16; moderate CoE) or health-related quality of life (HRQOL) at 12 months (mean difference -0.12, 95% CI -0.25-0.02; participants=2004, RCTs=11; moderate CoE), compared to MTURP. BTURP probably reduces TUR syndrome (relative risk [RR] 0.17, 95% CI 0.09-0.30; participants= 6,745, RCTs=44; moderate CoE) and blood transfusions (RR 0.42, 95% CI 0.30-0.59; participants=5727, RCTs=38; moderate CoE), compared to MTURP. BTURP may carry similar risk of urinary incontinence at 12 months (RR 0.20, 95% CI 0.01-4.06; participants=751; RCTs=4; low CoE), re-TURP (RR 1.02, 95% CI 0.44-2.40; participants=652, RCTs=6, I 2 =0%; low CoE) and erectile dysfunction (International Index of Erectile Function [IIEF-5]) at 12 months (mean difference 0.88, 95% CI -0.56-2.32; RCTs=3; moderate CoE), compared to MTURP., Conclusions: BTURP and MTURP probably improve urological symptoms to a similar degree. BTURP probably reduces TUR syndrome and blood transfusion slightly postoperatively. The moderate certainty of evidence available for primary outcomes suggests no need for further RCTs comparing BTURP and MTURP.

Macrophage-targeted therapy offers new options for intractable pancreatic ductal adenocarcinoma (PDAC), which has a low 5-year survival rate. However, the factors regulating the biological function and phenotype of macrophages in PDAC are incompletely understood. Here, we found that CD51 was positively associated with the poor prognosis of PDAC patients and was highly expressed on macrophages but not on pancreatic cancer cells. Subsequently, we found that CD51 was a marker of macrophages, which promoted the stemness of pancreatic cancer cells. Furthermore, knockdown of CD51 in macrophages drove macrophages toward an M1-like phenotype. Mechanistically, macrophage-expressed CD51 contributed to the acquisition of stemness traits of pancreatic cancer cells by regulating the TGF-β1/smad2/3 pathway. Our data demonstrate the central role played by macrophage-expressed CD51 in the acquisition of stemness traits of pancreatic cancer cells through the paracrine induction of TGF-β1. We first show the connection between the CD51/TGF-β1/smad2/3 axis and PDAC cancer stem cell properties and then indicate that CD51-targeted therapy is a new therapeutic modality for PDAC., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The design and synthesis of cost-effective and highperformance oxygen evolution reaction (OER) electrocatalysts for water splitting based on earth-abundant elements is urgent but challenging. A synergistic doping and architecture engineering strategy by nanosecond laser ablation is used to generate a unique kind of highly disordered Ni-doped Fe 3 O 4 nanoparticle clusters. Ni dopant and increased oxygen vacancies are simultaneously incorporated into Fe 3 O 4 frameworks and thereby modulate the electronic configuration for an optimal binding affinity towards OER intermediates. Nanoparticles with average size of around 5 nm assemble randomly during laser ablation and construct a fluffy and porous architecture, which not only optimizes the number of exposed active sites but also accelerates mass transfer. Consequently, Ni-doped Fe 3 O 4 clusters are revealed as a superior OER catalyst with a small overpotential of 272 mV at 10 mA cm -2 and a small Tafel slope of 39.4 mV dec -1 , surpassing almost all spinel Fe-based OER catalysts. This work provides a new strategy to fabricate advanced cation-doped metal oxide nanostructures for related energy applications., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Animal feed is prone to becoming infected with molds during production and storage, resulting in secondary metabolite mycotoxins, such as aflatoxin B 1 (AFB 1 ), T-2 toxins, deoxynivalenol (DON), and ochratoxin A (OTA), which are harmful to humans and animals. Selenium is an essential trace element for humans and animals, and it is also an effective antioxidant. Many studies have shown that selenium can reduce the damage caused by mycotoxins in animals. This article reviews the current literature on the antagonistic effects of selenium on AFB 1 , T-2, DON, and OTA toxicity.

Collection of water from the atmosphere is a potential route to alleviate the global water shortage. However, it is still difficult to find a strategy to collect sufficient water on a large surface and transport it all off the surface without additional energy input. Inspired by redbud leaves, herein, we proposed a new water-collecting configuration. This configuration utilizes an ultra-contrasting wettability venation network with hierarchical micro-nano structures as the skeleton and integrates the strategies evolved by cacti and beetles. This venation network was fabricated by the technology based on ultra-fast lasers. We achieved a near-unity efficiency in collecting and centralizing the condensed water on the entire surface with a large area. Remarkable water collection and centralization capability were obtained. The venation networks manifested the notable enhancements of ∼166%, ∼352% and ∼644% in water collection efficiency when compared with conventional superhydrophobic surfaces at the tilt angles of 90°, 60° and 30°, respectively. This configuration can work continuously at all tilt angles, even against gravity at a negative tilt angle of 90°. In addition, the venation network can maintain excellent water collecting capability even under very arid conditions. The principle and fabrication technology of this venation network make it possible to scale up a practical network device for mass water collection and may be useful for water desalination, heat transfer, microfluidics, lab-on-a-chip, distillation and many other applications.

Deoxynivalenol (DON) is a common contaminant of grain worldwide and is often detected in the human diet and animal feed. Selenium is an essential trace element in animals. It has many biological functions. The role of selenium in the body is mainly orchestrated by selenoprotein. Glutathione peroxidase (GPx) also exists widely in the body and has attracted much attention due to its high antioxidant capacity. In order to explore the effect of the GPx1 gene on toxicity of DON, in this study, we overexpressed or knockdown GPx1 in porcine splenic lymphocytes, then added different concentrations of DON (0.1025, 0.205, 0.41, and 0.82  μ g/mL) and sodium selenite (2  μ mol/L) to the culture system. Using various techniques, we detected antioxidant function, free radical content, cell apoptosis, and methylation-related gene expression to explore the effect of GPx1 expression on DON-induced cell damage. We also explored whether selenium can antagonize the toxicity of DON in these two cell models and revealed the protective effect of sodium selenite on DON-induced cell damage in GPx1-overexpressing or knockdown splenic lymphocytes. Finally, our findings revealed the following: (1) GPx1 can regulate the antioxidant capacity, apoptosis rate, and expression of DNA methylation-related genes in pig splenic lymphocytes. (2) Na 2 SeO 3 (2  μ mol/L) can regulate the antioxidant capacity, apoptosis rate, and expression of DNA methylation-related genes in pig splenic lymphocytes, and this effect is more significant in GPx1-overexpressing cells than in GPx1-knockdown cells. (3) DON can cause oxidative damage, apoptosis, and methylation injury in GPx1-overexpressing or knockdown pig splenic lymphocytes in a concentration-dependent manner. (4) Na 2 SeO 3 (2  μ mol/L) can antagonize the toxic effect of DON on GPx1-overexpressing or knockdown pig splenic lymphocytes. Our findings may have important implications for food/feed safety, human health, and environmental protection.

Deoxynivalenol (DON) is a cytotoxic mycotoxin that can cause cell damages. The main effect is to inhibit protein synthesis. Oxidative stress is one of the effects of DON. Selenium (Se) can ameliorate the cell damage caused by DON-induced oxidative stress, but it is unclear whether through selenoprotein glutathione peroxidase 1 (GPX1). We established GPX1-knockdown porcine spleen lymphocytes, and treated them with DON and Se. Untransfected porcine splenic lymphocytes (group P) and transfected cells (group M, GPX1 knockdown) were treated with or without DON (0.824, 0.412, 0.206, or 0.103 μg/mL, group D1-4), Se (Na 2 SeO 3 , 2 μM, group Se), or both (group SD1-4) for 6, 12, or 24 h. The cells were collected and the activities of SOD and CAT, levels of GSH, H 2 O 2 , malonaldehyde (MDA), total antioxidant capacity (T-AOC), and the inhibition of free hydroxyl radicals were determined. Levels of ROS were measured at 24 h. Compared with group P, the antioxidant capacity of group M was reduced. DON caused greater oxidative damage to the GPX1-knockdown porcine splenic lymphocytes than to the normal control cells. When Na 2 SeO 3 was combined with DON, it reduced the damage in the GPX1-knockdown porcine splenic lymphocytes, but less effectively than in the normal porcine splenic lymphocytes.

Background: Recently, various dynamically expressed lncRNAs are known to play critical roles in cancer progression. Small nucleolar RNA host genes (SNHG), a stable cytoplasmic lncRNA, which have been widely reported to act as an oncogene in non-small cell lung cancer (NSCLC). As an important member of SNHG, SNHG8 have been suggested to over-expressed in several cancer disease, while the biological function in NSCLC remains unclear., Purpose: Here we investigated the biological function and underlying mechanism of SNHG8 in human NSCLC., Patients and Methods: The relationship between SNHG8 expression and clinicopathologic characteristic in NSCLC patients were observed from January 2014 to December 2014 in 120 NSCLC patients. The expression of SNHG8 were analyzed by qRT-PCR assay in cancer tissues and cells. Cell proliferation ability were detected in NSCLC cells by CCK-8 assay. Flow cytometric analysis were performed to detected the cell apoptosis and cell cycle. Luciferase assay and Western blot assay were performed on NSCLC cells to detected the underlying mechanism of SNHG8 in NSCLC. Moreover, Tumor xenografts in nude mice were performed to detected the in vivo function of SNHG8., Results: SNHG8 was over-expressed in NSCLC tissues and cells. Patients with high SNHG8 expression have poorer overall survival (OS) and progression-free survival (PFS) than the patients with low SNHG8 expression. SNHG8 knockdown inhibited NSCLC cell proliferation in vitro and in vivo, arrested cell cycle in the G0/G1 phase via targeting miR-542-3p/CCND1/ CDK6, and induced cell apoptosis via activation of Caspase-3., Conclusion: SNHG8 negatively regulated miR-542-3p in NSCLC progression by regulating downstream effectors including CCND1 and CDK6. SNHG8 showed great potential for the application in the treatment of NSCLC., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Tumor-associated macrophages (TAMs) are the most abundant inflammatory infiltrates in the tumor microenvironment and contribute to lymph node (LN) metastasis. However, the precise mechanisms of TAMs-induced LN metastasis remain largely unknown. Herein, we identify a long noncoding RNA, termed Lymph Node Metastasis Associated Transcript 1 (LNMAT1), which is upregulated in LN-positive bladder cancer and associated with LN metastasis and prognosis. Through gain and loss of function approaches, we find that LNMAT1 promotes bladder cancer-associated lymphangiogenesis and lymphatic metastasis. Mechanistically, LNMAT1 epigenetically activates CCL2 expression by recruiting hnRNPL to CCL2 promoter, which leads to increased H3K4 tri-methylation that ensures hnRNPL binding and enhances transcription. Furthermore, LNMAT1-induced upregulation of CCL2 recruits macrophages into the tumor, which promotes lymphatic metastasis via VEGF-C excretion. These findings provide a plausible mechanism for LNMAT1-modulated tumor microenvironment in lymphatic metastasis and suggest that LNMAT1 may represent a potential therapeutic target for clinical intervention in LN-metastatic bladder cancer.

Thyroid transcription factor-1 (TTF-1) is routinely used in the diagnosis of lung carcinoma and the subclassification of non-small cell lung cancer (NSCLC) in combination with other markers. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are particularly effective in NSCLC patients harboring active EGFR mutations. EGFR protein is a poor prognostic factor for NSCLC patients. The relationship between TTF-1 expression and EGFR mutation and EGFR expression has not been well documented. The aim of this study was to investigate the relationship between TTF-1 and EGFR expression and mutation, and the clinical significance in lung adenocarcinoma. We analyzed TTF-1 expression, EGFR expression and mutation in 213 cases of lung adenocarcinoma. TTF-1 and EGFR expression levels were detected by immunohistochemical staining with monoclonal antibodies. EGFR mutations in exon 18, 19, 20 and 21 were assayed by the scorpion amplification refractory mutation system (ARMS) method. Forty-eight patients with EGFR mutations in exon 19 or 21 were detected from 91 patients with TTF-1 strong positive expression (3+) (52.74%), and 35 patients were detected with either exon 19 or 21 mutations from 54 patients with both TTF1 and EGFR positive expression (64.81%). Our data indicate that TTF-1 expression was positively related to EGFR mutation ( P < 0.001) and EGFR expression ( P < 0.001). EGFR expression level was positively related to its mutation ( P = 0.003). These results indicate TTF-1 and EGFR positive lung adenocarcinomas frequently harbor EGFR mutations., Competing Interests: None., (IJCEP Copyright © 2018.)

Deoxynivalenol (DON) is a mycotoxin that causes immunosuppression, especially in swine. Selenium (Se) is essential for proper functioning of the immune system in animals. However, little is known about the effects of DON and Se on cytokine or immunoglobulin production in piglets. Here, we addressed this gap by examining piglet splenic lymphocyte responses in vitro. Cells were stimulated with concanavalin A, a T cell stimulatory lectin, in the absence or presence of DON (0.1, 0.2, 0.4, and 0.8 μg/mL), Se (Na 2 SeO 3 , 2 μM), or combinations of Se 2 μM and DON 0.1-0.8 μg/mL for 12, 24, or 48 h. At each time point, supernatants and cells were collected and the expression of cytokine and immunoglobulin protein and mRNA was examined. Compared with control and Se-alone treatments, DON exposure significantly and dose dependently decreased the expression levels of IL-2, IL-4, IL-6, IL-10, IFN-γ, IgG, and IgM mRNA and protein. By contrast, co-treatment with DON + Se significantly increased the mRNA and protein levels of all factors examined, except IL-4 and IL-6, compared with DON treatment alone. The results of this investigation demonstrate that Se has the potential to counteract DON-induced immunosuppression in piglets and is a promising treatment for DON-mediated toxicity.

Long non-coding RNAs (lncRNAs) have been identified as significant regulators in cancer progression. Positive feedback loops between lncRNAs and transcription factors have attracted increasing attention. Akt pathway plays a crucial role in bladder cancer growth and recurrence. In the present study, we demonstrate a novel regulatory pattern involving FOXD2-AS1, Akt, and E2F1. FOXD2-AS1 is highly expressed in bladder cancer and is associated with tumor stage, recurrence, and poor prognosis. Further experiments showed that FOXD2-AS1 promotes bladder cancer cell proliferation, migration, and invasion in vitro and in vivo. Microarray analysis demonstrated that FOXD2-AS1 negatively regulates the expression of Tribbles pseudokinase 3 (TRIB3), a negative regulator of Akt. Mechanistically, FOXD2-AS1 forms an RNA-DNA complex with the promoter of TRIB3, the transcriptional activity of which is subsequently repressed, and leads to the activation of Akt, which further increases the expression of E2F1, a vital transcription factor involved in the G/S transition. Interestingly, E2F1 could bind to the FOXD2-AS1 promoter region and subsequently enhance its transcriptional activity, indicating that FOXD2-AS1/Akt/E2F1 forms a feedback loop. In summary, this regulatory pattern of positive feedback may be a novel target for the treatment of bladder cancer and FOXD2-AS1 has the potential to be a new recurrence predictor.

The prognosis for bladder cancer patients with lymph node (LN) metastasis is dismal and only minimally improved by current treatment modalities. Elucidation of the molecular mechanisms that underlie LN metastasis may provide clinical therapeutic strategies for LN-metastatic bladder cancer. Here, we report that a long noncoding RNA LINC00958, which we have termed bladder cancer-associated transcript 2 (BLACAT2), was markedly upregulated in LN-metastatic bladder cancer and correlated with LN metastasis. Overexpression of BLACAT2 promoted bladder cancer-associated lymphangiogenesis and lymphatic metastasis in both cultured bladder cancer cell lines and mouse models. Furthermore, we demonstrate that BLACAT2 epigenetically upregulated VEGF-C expression by directly associating with WDR5, a core subunit of human H3K4 methyltransferase complexes. Importantly, administration of an anti-VEGF-C antibody inhibited LN metastasis in BLACAT2-overexpressing bladder cancer. Taken together, these findings uncover a molecular mechanism in the lymphatic metastasis of bladder cancer and indicate that BLACAT2 may represent a target for clinical intervention in LN-metastatic bladder cancer.

Background : Most patients receiving docetaxel-based chemotherapy for castration resistant prostate cancer (CRPC) will eventually progress, and the optimal interventions for these patients are controversial. The objective of our study is to evaluate the clinical efficacy and safety of pharmacological interventions for CRPC patients progressing after docetaxel-based chemotherapy. Methods : A systematic review and Bayesian network meta-analysis of the literature was carried out according to standard methods. Major electronic databases including PubMed, Web of Science and Embase were searched until Jan 2017. Hazard ratios (HRs) and odds ratios (ORs) with corresponding 95% credible intervals (CrIs) were used to estimate the association. Results : 17 Randomized Controlled Trials (RCTs) comprising 14 different interventions with 12347 patients were enrolled. Compared with control arms, Abiraterone Acetate (HR: 0.70, 95%CrI: 0.63-0.79), Cabazitaxel (HR: 0.70, 95%CrI: 0.51-0.95) and Enzalutamide (HR: 0.63, 95%CrI: 0.53-0.75) presented similar benefits in term of OS. Enzalutamide showed superiority over PFS and PSA response with a highest probability to rank 1. Moreover, sensitivity analysis showed that Abiraterone Acetate (HR: 0.71, 95%CrI: 0.63-0.78) exhibited the most efficacious intervention of being rank 1 in term of OS compared with control arms, followed by Cabazitaxel and Cetuximab. On the other hand, Abiraterone Acetate (OR: 0.86, 95%CrI: 0.35-2.03) presented no significant toxicities compared with control arms. Conclusions : Our results demonstrated that Abiraterone Acetate might be the optimal intervention for CRPC patients after docetaxel failure with acceptable tolerability. Future well-designed RCTs and systematic reviews are needed to validate these findings., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Our previous study demonstrated that long non-coding RNA (lncRNA) HOTTIP was maximally expressed in PDAC, and promoted cancer cell progression and epithelial to mesenchymal transition (EMT). Numerous studies indicated that lncRNAs or EMT supported cancer stem cells. However, the role of HOTTIP in pancreatic cancer stem cells (PCSCs) remains unclear. Here, we evaluated the role and mechanism of HOTTIP in PCSCs. First, we analyzed the relationship between HOTTIP expression and overall or disease-free survival in 90 patients with PDAC after radical resection. Patients with higher HOTTIP expression had shorter disease-free survival and overall survival than those with lower expression. Expression of HOTTIP and other lncRNAs was detected in PCSCs and non-PCSCs by laser capture microdissection (LCM). HOTTIP was highly expressed in PCSCs. In addition, in vitro assays showed that HOTTIP alterations affected stemness, including sphericity, tumorigenesis, and stem factors (LIN28, NANOG, OCT4, and SOX2) and markers (ALDH1, CD44, and CD133). Mechanistically, HOTTIP mediated HOXA9 to enhance the Wnt/β-catenin pathway by binding to WDR5 in PCSCs. In vivo results showed that HOTTIP or HOXA9 alterations influenced stemness. Our results indicate that the HOTTIP/WDR5/HOXA9/Wnt axis contributes to PCSC stemness and is a potential therapeutic target for PDAC., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Hypoxia-inducible factor-2α (HIF-2α) plays an important role in increasing cancer progression and distant metastasis in a variety of tumour types. We aimed to investigate its biological function and clinical significance in human pancreatic ductal adenocarcinoma (PDAC). A total of 283 paired PDAC tissues and adjacent normal tissues were collected from patients who underwent surgery or biopsy at Sun Yat-sen Memorial Hospital between February 2004 and October 2016. In this study, we noted that HIF-2α expression was significantly up-regulated in PDAC, positively associated with disease stage, lymph-node metastasis and patient survival, and identified as an independent prognostic factor of PDAC patients. We demonstrated that HIF-2α silencing could reduce proliferation, migration and invasion of PDAC cells in vitro. The similar effect on growth was demonstrated in vivo. Furthermore, we noted that knock-down of HIF-2α significantly decreased the expression of glutamate oxaloacetate transaminase 1 (GOT1). Importantly, we confirmed that the PI3K/mTORC2 pathway promoted GOT1 expression by targeting HIF-2α. Our study validated HIF-2α was an important factor in PDAC progression and poor prognosis and may promote non-canonical glutamine metabolism via activation of PI3K/mTORC2 pathway. Targeting HIF-2α represents a novel prognostic biomarker and therapeutic target for patients with PDAC., (© 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

The transition from androgen-dependent to metastatic castration-resistant prostate cancer (PCa) is a lethal event of uncertain molecular aetiology. Our previous studies demonstrated that L-plastin is involved in PCa invasion and metastasis and is upregulated by androgen and oestrogen in the hormone-dependent PCa cell line LNCaP. We recently found that L-plastin expression is consistently activated even after androgen deprivation, suggesting that androgen-independent transcription factors may regulate its expression. Herein, we performed sequential deletion and luciferase analysis of the L-plastin promoter and found that an androgen-independent regulatory factor prominently located in the region close to the transcription initiation site (-216 to +118) may facilitate L-plastin upregulation. AP4 was then identified as the relevant transcription activator that directly binds to the L-plastin promoter, as confirmed by EMSAs, supershift assays and CHIP-qPCR experiments. Moreover, we determined that the AP4/L-plastin axis is regulated by the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, contributing to PCa metastasis and castration resistance. Furthermore, we found that AP4 promotes PCa metastasis by upregulating L-plastin expression in vitro and in vivo. We collected a total of 136 PCa tissues and corresponding adjacent normal tissues from patients who underwent prostatectomy at Sun Yat-Sen Memorial Hospital from 2005 to 2015 and measured AP4 and L-plastin protein levels by immunohistochemistry. The results showed that AP4 levels strongly correlated with those of its downstream target gene L-plastin, were significantly upregulated in PCa tissues, were positively correlated with lymph node metastasis and Gleason scores over 7, and were an independent prognostic factor for patient survival. In summary, these findings support a plausible mechanism by which the AP4/L-plastin axis is regulated by the PI3K/AKT pathway in human PCa and may represent a novel therapeutic target in PCa treatment.

Castration-resistant prostate cancer (CRPC) that occurs after the failure of androgen deprivation therapy is the leading cause of deaths in prostate cancer patients. Thus, there is an obvious and urgent need to fully understand the mechanism of CRPC and discover novel therapeutic targets. Long noncoding RNAs (lncRNAs) are crucial regulators in many human cancers, yet their potential roles and molecular mechanisms in CRPC are poorly understood. In this study, we discovered that an lncRNA HOXD-AS1 is highly expressed in CRPC cells and correlated closely with Gleason score, T stage, lymph nodes metastasis, and progression-free survival. Knockdown of HOXD-AS1 inhibited the proliferation and chemo-resistance of CRPC cells in vitro and in vivo. Furthermore, we identified several cell cycle, chemo-resistance, and castration-resistance-related genes, including PLK1, AURKA, CDC25C, FOXM1, and UBE2C, that were activated transcriptionally by HOXD-AS1. Further investigation revealed that HOXD-AS1 recruited WDR5 to directly regulate the expression of target genes by mediating histone H3 lysine 4 tri-methylation (H3K4me3). In conclusion, our findings indicate that HOXD-AS1 promotes proliferation, castration resistance, and chemo-resistance in prostate cancer by recruiting WDR5. This sheds a new insight into the regulation of CRPC by lncRNA and provides a potential approach for the treatment of CRPC., (Copyright © 2017. Published by Elsevier Inc.)

Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is an essential RNA- and DNA-binding protein that regulates diverse biological events, especially DNA transcription. hnRNPK overexpression is related to tumorigenesis in several cancers. However, both the expression patterns and biological mechanisms of hnRNPK in bladder cancer are unclear. We investigated hnRNPK expression by immunohistochemistry in 188 patients with bladder cancer, and found that hnRNPK expression levels were significantly increased in bladder cancer tissues and that high-hnRNPK expression was closely correlated with poor prognosis. Loss- and gain-of-function assays demonstrated that hnRNPK promoted proliferation, anti-apoptosis, and chemoresistance in bladder cancer cells in vitro, and hnRNPK knockdown suppressed tumorigenicity in vivo. Mechanistically, hnRNPK regulated various functions in bladder cancer by directly mediating cyclin D1, G0/G1 switch 2 (G0S2), XIAP-associated factor 1, and ERCC excision repair 4, endonuclease catalytic subunit (ERCC4) transcription. In conclusion, we discovered that hnRNPK plays an important role in bladder cancer, suggesting that it is a potential prognostic marker and a promising target for treating bladder cancer., (© 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Objectives: The optimal concentration of individual vitamin D intake for preventing bladder cancer has not, to our knowledge, been defined. To evaluate the comparative efficacy of different serum 25-hydroxyvitamin D concentrations in preventing bladder cancer, we conducted a systematic search of the literature published up to April 2015., Methods: We applied a pairwise meta-analysis to estimate direct evidence from intervention-control studies and a network meta-analysis within a Bayesian framework to combine direct and indirect evidence. Moreover, a dose-response curve was utilized to predict the optimal median serum 25-hydroxyvitamin D concentration based on the odds ratio (OR) for each quintile concentration., Methods: Seven studies of a total of 90757 participants, including 2509 bladder cancer patients, were included. Two prospective cohort studies with 57 591 participants and 494 bladder cancer patients, and five case-control studies with 33 166 participants and 2264 bladder cancer patients. From the network meta-analysis, we observed that sufficient serum 25-hydroxyvitamin D concentrations (>75 nmol/L) were superior to all other 25-hydroxyvitamin D concentrations in decreasing the risk of bladder cancer: OR = 0.68 and 95% credible interval (CrI) 0.52 to 0.87 compared with severely deficient concentrations (<25 nmol/L); OR = 0.65 and 95% CrI 0.49 to 0.86 compared with moderately deficient concentrations (25-37.5 nmol/L); OR = 0.61 and 95% CrI 0.47 to 0.80 compared with slightly deficient concentrations (37.5-50 nmol/L); and OR = 0.65 and 95% CrI 0.48 to 0.85 compared with insufficient concentrations (50-75 nmol/L). In addition, we noted a roughly inverse correlation between bladder cancer risk and 25-hydroxyvitamin D concentrations (R(2) = 0.98, P = 0.007)., Conclusions: Ensuring sufficient serum 25-hydroxyvitamin D concentrations might play an important role in decreasing the risk of bladder cancer. The serum 25-hydroxyvitamin D concentration ≥74 nmol/L was associated with a 60% lower risk of bladder cancer incidence., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The L-plastin gene is involved in the invasion and metastasis of prostate cancer. However, the molecular mechanisms underlying L-plastin transcription are unclear. We hypothesize that the occurrence of polymorphic genetic variations in the L-plastin promoter might affect an individual's susceptibility to prostate cancer. In this study, we identified a single nucleotide polymorphism (SNP) at position -1,687 in the L-plastin promoter by genotype sequencing. The SNP -1,687 showed different transcriptional activity in the luciferase assay in vitro. The TRANSFAC software was applied to predict the multiple cis-elements, and luciferase assay was used to further identify the L-plastin regulatory region. We performed EMSAs, supershift assays and ChIP-qPCR demonstrated that the transcriptional suppressor NKX3.1 binds to the SNP site of the L-plastin promoter. SNP -1,687 (T/T) led to an increase in the affinity of NKX3.1 for L-plastin promoter, resulted in lower levels of L-plastin RNA and protein expression. Furthermore, we collected and sequenced samples from 640 individuals (372 prostate cancer patients and 268 healthy controls) from 2000 to 2013. The results showed that SNP -1,687 (T/T) occurred more frequently in the healthy individuals than that in the prostate cancer patients compared to SNP -1,687 (C/C). Similarly, SNP -1,687 (T/T) genotype occurred more frequently compared to SNP -1,687 (C/C) genotype in the patients with low and moderately differentiated tumors. In conclusion, SNP -1,687, located in the NKX3.1 binding site within the L-plastin promoter, might reduce the expression of L-plastin and potentially decrease the tumorigenesis and progression of prostate cancer. This SNP could be a potential prognostic factor for prostate cancer., (© 2015 UICC.)

Several reports suggest that gemcitabine (GEM) plus S-1 combination (GS) is associated to prolong the survival in patients with unresectable pancreatic cancer (PC). We conducted a systemic review and meta-analysis of studies comparing the safety and efficacy of GS versus GEM.Summary data from randomized trials and retrospective studies were searched in PubMed, EMBASE, Web of Science, and the Cochrane Library. Statistical analyses were conducted to calculate the hazard ratios (HRs) and relative risk (RR) with 95% confidence intervals (CIs) using random-effects models. Subgroup analyses based on the chemotherapy cycles were performed to explore the efficacy and toxicity for therapy. Sensitivity analyses were conducted by removing specific studies to assess the effects of study quality.Between January 2004 and August 2012, 4 RCTs and 2 retrospective studies including a total of 1025 cases were identified. The overall survival (OS) (HR: 0.82; 95% CI, 0.70-0.96; P = 0.01) and progression-free survival (PFS) (HR: 0.65; 95% CI, 0.55-0.77; P < 0.001) for the GS arm were significantly longer than the GEM arm. The differences in objective response rate (ORR) (RR: 1.24; 95% CI, 1.17-1.33; P < 0.001) and disease control rate (DCR) were also better in the GS arm (RR: 1.37; 95% CI, 1.19-1.59; P < 0.001). Grades 3 to 4 toxicities in both the groups were similar except neutropenia and diarrhea, which were more frequent in the GS arm (P < 0.001). In the subgroup analysis, the cycle for chemotherapy every 4 weeks has equivalent efficacy and less toxicity than regimens every 3 weeks in the GS arm.The current meta-analysis suggested that GEM significantly prolonged OS and PFS when added to S-1 combination in patients with unresectable PC. GS therapy also offers better ORR and DCR than GEM monotherapy and no unexpected toxicity was evident.

WD repeat domain 5 (WDR5) plays an important role in various biological functions through the epigenetic regulation of gene transcription (Wysocka et al., 2005 [1]; Sandstrom et al., 2014[2]; Ang et al., 2011[3]). Recently, our study found that WDR5 was upregulated in bladder cancer tissues, promoted bladder cancer cell proliferation, self-renewal and chemoresistance to cisplatin in bladder cancer cells in vitro, and tumor growth in vivo (Chen et al., 2015). To gain a molecular understanding of the role of WDR5 in promoting bladder cancer, we performed a genome-wide analysis on WDR5 knockdown by microarray gene expression profiling. Here we provide detailed experimental methods and analysis for the microarray data, which have been deposited into Gene Expression Omnibus (GEO): GSE59132.

Purpose: In men with adverse prognostic factors (APFs) after radical prostatectomy (RP), the most appropriate timing to administer radiotherapy remains a subject for debate. We conducted a systemic review and meta-analysis to evaluate the therapeutic strategies: adjuvant radiotherapy (ART) and salvage radiotherapy (SRT)., Materials and Methods: We comprehensively searched PubMed, EMBASE, Web of Science and the Cochrane Library and performed the meta-analysis of all randomized controlled trials (RCTs) and retrospective comparative studies assessing the prognostic factors of ART and SRT., Results: Between May 1998 and July 2012, 2 matched control studies and 16 retrospective studies including a total of 2629 cases were identified (1404 cases for ART and 1185 cases for SRT). 5-year biochemical failure free survival (BFFS) for ART was longer than that for SRT (Hazard Ratio [HR]: 0.37; 95% CI, 0.30-0.46; p<0.00001, I(2) = 0%). 3-year BFFS was significantly longer in the ART (HR: 0.38; 95% CI, 0.28-0.52; p<0.00001, I(2) = 0%). Overall survival (OS) was also better in the ART (RR: 0.53; 95% CI, 0.41-0.68; p<0.00001, I(2) = 0%), as did disease free survival (DFS) (RR: 0.53; 95% CI, 0.43-0.66; p<0.00001, I(2)  = 0%). Exploratory subgroup analysis and sensitivity analysis revealed the similar results with original analysis., Conclusion: ART therapy offers a safe and efficient alternative to SRT with longer 3-year and 5-year BFFS, better OS and DFS. Our recommendation is to suggest ART for patients with APFs and may reduce the need for SRT. Given the inherent limitations of the included studies, future well-designed RCTs are awaited to confirm and update this analysis.