Metrnl inhibits choroidal neovascularization by attenuating the choroidal inflammation via inactivating the UCHL-1/NF-κB signaling pathway.

Objective: Choroidal neovascularization (CNV) represents the predominant form of advanced wet Age-related Macular Degeneration (wAMD). Macrophages play a pivotal role in the pathological progression of CNV. Meteorin-like (Metrnl), a novel cytokine known for its anti-inflammatory properties in macrophages, is the focus of our investigation into its mechanism of action and its potential to impede CNV progression. Methods: Cell viability was evaluated through CCK-8 and EdU assays following Metrnl treatment. Expression levels of inflammatory cytokines and proteins were assessed using quantitative reverse-transcription polymerase chain reaction(qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blot techniques. Protein-protein interactions were identified through protein mass spectrometry and co-immunoprecipitation (Co-IP). Additionally, in vivo and in vitro neovascularization models were employed to evaluate angiogenesis. Results: Our results revealed downregulated Metrnl levels in the choroid-sclera complex of CNV mice, the aqueous humor of wAMD patients, and activated macrophages. Metrnl overexpression demonstrated a reduction in pro-inflammatory cytokine production, influenced endothelial cell function, and suppressed angiogenesis in choroid explants and CNV models. Through protein mass spectrometry and Co-IP, we confirmed Metrnl binds to UCHL-1 to modulate the NF-κB signaling pathway. This interaction inhibited the transcription and expression of pro-inflammatory cytokines, ultimately suppressing angiogenesis. Conclusion: In summary, our findings indicate that Metrnl down-regulates macrophage pro-inflammatory cytokine secretion via the UCHL-1/NF-κB signaling pathway. This mechanism alleviates the inflammatory microenvironment and effectively inhibits choroidal neovascularization.

Self-Organizing Type-2 Fuzzy Double Loop Recurrent Neural Network for Uncertain Nonlinear System Control.

Nonlinear systems, such as robotic systems, play an increasingly important role in our modern daily life and have become more dominant in many industries; however, robotic control still faces various challenges due to diverse and unstructured work environments. This article proposes a double-loop recurrent neural network (DLRNN) with the support of a Type-2 fuzzy system and a self-organizing mechanism for improved performance in nonlinear dynamic robot control. The proposed network has a double-loop recurrent structure, which enables better dynamic mapping. In addition, the network combines a Type-2 fuzzy system with a double-loop recurrent structure to improve the ability to deal with uncertain environments. To achieve an efficient system response, a self-organizing mechanism is proposed to adaptively adjust the number of layers in a DLRNN. This work integrates the proposed network into a conventional sliding mode control (SMC) system to theoretically and empirically prove its stability. The proposed system is applied to a three-joint robot manipulator, leading to a comparative study that considers several existing control approaches. The experimental results confirm the superiority of the proposed system and its effectiveness and robustness in response to various external system disturbances.

Actor-Critic With Synthesis Loss for Solving Approximation Biases.

Approximation biases of value functions are considered a key problem in reinforcement learning (RL). In particular, existing RL algorithms are hindered by overestimation and underestimation biases, i.e., value mismatching between RL's actual returns and action-value approximations limits the performance of RL algorithms. In this article, we first develop a new synthesis loss function for RL's action-value estimation integrating a regularization term and a modified "clipped double Q -learning" structure for solving overestimation and underestimation biases. To minimize the differences between action-value estimations and actual returns in RL, we develop a new discrepancy function to determine the type and magnitude of approximation biases. Then, two coefficients embedded in the synthesis loss are automatically tuned by minimizing the discrepancy function during training to minimize approximation biases. We further design a new actor-critic (AC) algorithm, named AC with synthesis loss (ACSL), by integrating the synthesis loss function and an error-controlled mechanism. Experimental results on continuous control tasks illustrate that the proposed ACSL algorithm outperforms other cutting-edge RL methods in many tasks and that the proposed synthesis loss function is easily implemented into other algorithms and significantly reduces approximation biases while improving performance. The proposed method can successfully handle many complex continuous control tasks and can greatly outperform other state-of-the-art algorithms on most tasks.

A new method for accurate inversion of Forel-Ule index using MODIS images - revealing the water color evolution in China's large lakes and reservoirs over the past two decades.

The Forel Ule water color index (FUI) based on satellite inversion can characterize the comprehensive characteristics of water quality on a large spatiotemporal scale. The high-frequency observations and rich historical data of the MODIS surface reflectance product (MODIS-500 m) provide important data support for monitoring the FUI of inland lakes. However, MODIS-500 m has only three bands in the visible light range, resulting in significant uncertainty in FUI inversion. To address this problem, this study developed an improved FUI inversion model using 500 synthetic spectra covering natural waters. The model, with a performance threshold set at 170° (FUI = 8), used a segmented algorithm across the entire color space. Validated with on-site measurement datasets (3500 samples), the model exhibited excellent performance, with mean relative error (MRE) and root mean square error (RMSE) of 1.71 % and 3.63°, respectively. Compared to existing models, it was more suitable for long-term FUI inversion in various types of lakes, particularly in eutrophic regions. Subsequently, the model was applied to MODIS-500 m observations from 2000 to 2022, revealing the spatiotemporal dynamics of FUI in 180 large lakes and reservoirs (hereinafter referred to as lakes) in China. The results indicated that the long-term mean FUI in the study area was 9, with 7 and 12 in the western and eastern regions, respectively, showing a distinct spatial distribution of "blue in the west and green in the east." The mean change rate of hue angle for all lakes was -0.085°/yr, showing an overall decreasing trend. Environmental factors' relative contributions to long-term water color changes in each lake region were quantified using the multiple general linear model (GLM). Although each lake region exhibited different driving forces, they were primarily influenced by vegetation, lake surface area, and anthropogenic factors. Additionally, the seasonal types of lake water color were analyzed, with the west and east showing opposite patterns, reflecting the significant influence of topographic features and seasonal changes in climate on water color. The research results provide techniques for accurate inversion of FUI using MODIS-500 m data, while deepening the understanding of long-term water color changes in inland lakes in China.

Accurate Finite Element Simulations of Dynamic Behaviour: Constitutive Models and Analysis with Deep Learning.

Owing to the challenge of capturing the dynamic behaviour of metal experimentally, high-precision numerical simulations have become essential for analysing dynamic characteristics. In this study, calculation accuracy was improved by analysing the impact of constitutive models using the finite element (FE) model, and the deep learning (DL) model was employed for result analysis. The results showed that FE simulations with these models effectively capture the elastic-plastic response, and the ZA model exhibits the highest accuracy, with a 26.0% accuracy improvement compared with other models at 502 m/s for Hugoniot elastic limit (HEL) stress. The different constitutive models offer diverse descriptions of stress during the elastic-plastic response because of temperature effects. Concurrently, the parameters related to the yield strength at quasi-static influence the propagation speed of elastic waves. Calculation show that the yield strength at quasi-static of 6061 Al adheres to y = ax + b for HEL stress. The R-squared (R2) and mean absolute error (MAE) values of the DL model for HEL stress predictions are 0.998 and 0.0062, respectively. This research provides a reference for selecting constitutive models for simulation under the same conditions.

Efficacy of microwave ablation with parallel acupuncture guided by ultrasound in treating single hepatocellular carcinoma in high-risk areas: A retrospective analysis of 155 patients.

OBJECTIVE: To investigate the safety and short- and long-term efficacy of ultrasound-guided microwave ablation (MWA) with parallel acupuncture for treating single hepatocellular carcinoma (HCC) in high-risk areas. METHODS: Retrospective analysis was performed on 155 patients with single hepatocellular carcinoma who underwent microwave ablation in our hospital between December 2015 and September 2016. Patients with a tumor distance of ≤5 mm from the risk area were included in the observation group. Patients with a tumor distance of >5 mm from the risk area were placed in the control group. The patients' preoperative general health status, tumor site, tumor size, follow-up data, disease-free survival rate, overall survival rates, local tumor progression, and intrahepatic distant recurrence rate were collected and analyzed. RESULTS: The 1-, 3-, and 5-year overall survival rates for the observation group were 91.8%, 75.5%, and 59.2%, respectively. The 1-, 3-, and 5-year overall survival rates for the control group were 97.2%, 84.0%, and 66.0%, respectively. There were no significant differences between the two groups (P = 0.522). A tumor size of ≤20 mm (HR = 0.488, 95% CI = 0.254-0.940, P = 0.032) was an independent risk factor affecting the overall survival of patients with solitary HCC treated with MWA. The 1-, 3-, and 5-year recurrence-free survival rates for the observation group were 59.2%, 28.6%, and 18.4%, respectively, and those for the control group were 79.2%, 43.4%, and 31.1%, respectively. There was a statistical difference between the two groups (P = 0.007). Tumor size ≤20 mm (HR = 0.468, 95% CI = 0.303-0.723, P = 0.001), tumor location in a risk area (HR = 1.662, 95% CI = 1.121-2.465, P = 0.011), and an α-fetoprotein (AFP) level of <200 ug/L (HR = 0.612, 95% CI = 0.386-0.970, P = 0.036) are independent factors affecting the recurrence-free survival of MWA treatment for HCC. CONCLUSION: Microwave ablation with parallel acupuncture guided by ultrasound is a safe and effective treatment for single hepatocellular carcinoma in high-risk areas.

Single dual-specific anti-PD-L1/TGF-ß antibody synergizes with chemotherapy as neoadjuvant treatment for pancreatic ductal adenocarcinoma: a preclinical experimental study.

AIMS: Chemotherapy resistance is an important cause of neoadjuvant therapy failure in pancreatic ductal adenocarcinoma (PDAC). BiTP (anti-PD-L1/TGF-ß bispecific antibody) is a single antibody that can simultaneously and dually target transforming growth factor-beta (TGF-ß) and programmed cell death ligand 1 (PD-L1). We attempted in this study to investigate the efficacy of BiTP in combination with first-line chemotherapy in PDAC. METHODS: Preclinical assessments of BiTP plus gemcitabine and nab-paclitaxel were completed through a resectable KPC mouse model (C57BL/6J). Spectral flow cytometry, tissue section staining, enzyme-linked immunosorbent assays, Counting Kit-8, transwell, and Western blot assays were used to investigate the synergistic effects. RESULTS: BiTP combinatorial chemotherapy in neoadjuvant settings significantly downstaged PDAC tumors, enhanced survival, and had a higher resectability for mice with PDAC. BiTP was high affinity binding to targets and reverse chemotherapy resistance of PDAC cells. The combination overcame immune evasion through reprogramming tumor microenvironment via increasing penetration and function of T cells, natural killer cells, and dendritic cells and decreasing the function of immunosuppression-related cells as regulatory T cells, M2 macrophages, myeloid-derived suppressor cells, and cancer-associated fibroblasts. CONCLUSION: Our results suggest that the BiTP combinatorial chemotherapy is a promising neoadjuvant therapy for PDAC.

Effectiveness of Butorphanol in alleviating intra- and post-operative visceral pain following microwave ablation for hepatic tumor: a dual-central, randomized, controlled trial.

Many patients who underwent hepatic percutaneous microwave ablation (MWA) reported experiencing pain during the procedure. This study utilized a well-designed multicentral, randomized, and placebo-controlled format to investigate the effects of Butorphanol. Patients who underwent MWA were randomly assigned to either Butorphanol or normal saline group. The primary outcomes of the study were assessed by measuring the patients' intraoperative pain levels using a 10-point visual analog scale (VAS). Secondary outcomes included measuring postoperative pain levels at the 6-h mark (VAS) and evaluating comprehensive pain assessment outcomes. A total of 300 patients were divided between the control group (n = 100) and the experimental group (n = 200). Butorphanol showed statistically significant reductions in intraoperative pain levels compared to the placebo during surgery (5.00 ± 1.46 vs. 3.54 ± 1.67, P < 0.001). Significant differences were observed in postoperative pain levels at the 6-h mark and in the overall assessment of pain (1.39 + 1.21 vs. 0.65 + 0.81, P < 0.001). Butorphanol had a significant impact on reducing the heart rate of patients. The empirical evidence supports the effectiveness of Butorphanol in reducing the occurrence of visceral postoperative pain in patients undergoing microwave ablation for hepatic tumor. Furthermore, the study found no noticeable impact on circulatory and respiratory dynamics.

Zirconia Toughened Alumina Ceramics via Forming Intragranular Structure.

The distribution of second phase particles in the microstructure of composite ceramics affects the mechanical properties, and the intragranular structures often result in better properties compared to the intergranular structures. However, it is difficult to obtain composite ceramics with intragranular structure by conventional route. To produce composite ceramics with an intragranular structure in a simpler route. In this work, starting powders with different phase compositions were obtained by the co-precipitation method, and zirconia toughened alumina (ZTA) composite ceramics were prepared with these starting powders by spark plasma sintering (SPS). The results show that it is easier to fabricate ZTA composite ceramics with an intragranular structure by using composite powders containing amorphous or transition phase Al2O3 as starting materials. The phase composition of the powder prepared by the co-precipitation method after calcination at 1100 °C is θ-Al2O3 and t-ZrO2, and the average grain size after sintering at 1500 °C is 1.04 ± 0.28 µm, and the maximum Vickers hardness and fracture toughness of the specimens reach 19.37 ± 0.43 GPa and 6.18 ± 0.06 MPa·m1/2, respectively. The ZrO2 particles were the core of crystallization and grow together with the Al2O3 matrix, forming the intragranular structure of ZTA ceramics. This work may provide a new idea for preparing composite ceramics with intragranular structure.

Uncovering the Over-Smoothing Challenge in Image Super-Resolution: Entropy-Based Quantification and Contrastive Optimization.

PSNR-oriented models are a critical class of super-resolution models with applications across various fields. However, these models tend to generate over-smoothed images, a problem that has been analyzed previously from the perspectives of models or loss functions, but without taking into account the impact of data properties. In this paper, we present a novel phenomenon that we term the center-oriented optimization (COO) problem, where a model's output converges towards the center point of similar high-resolution images, rather than towards the ground truth. We demonstrate that the strength of this problem is related to the uncertainty of data, which we quantify using entropy. We prove that as the entropy of high-resolution images increases, their center point will move further away from the clean image distribution, and the model will generate over-smoothed images. Implicitly optimizing the COO problem, perceptual-driven approaches such as perceptual loss, model structure optimization, or GAN-based methods can be viewed. We propose an explicit solution to the COO problem, called Detail Enhanced Contrastive Loss (DECLoss). DECLoss utilizes the clustering property of contrastive learning to directly reduce the variance of the potential high-resolution distribution and thereby decrease the entropy. We evaluate DECLoss on multiple super-resolution benchmarks and demonstrate that it improves the perceptual quality of PSNR-oriented models. Moreover, when applied to GAN-based methods, such as RaGAN, DECLoss helps to achieve state-of-the-art performance, such as 0.093 LPIPS with 24.51 PSNR on 4× downsampled Urban100, validating the effectiveness and generalization of our approach.

A toroidal SAW gyroscope with focused IDTs for sensitivity enhancement.

A surface acoustic wave (SAW) gyroscope measures the rate of rotational angular velocity by exploiting a phenomenon known as the SAW gyroscope effect. Such a gyroscope is a great candidate for application in harsh environments because of the simplification of the suspension vibration mechanism necessary for traditional microelectromechanical system (MEMS) gyroscopes. Here, for the first time, we propose a novel toroidal standing-wave-mode SAW gyroscope using focused interdigitated transducers (FIDTs). Unlike traditional SAW gyroscopes that use linear IDTs to generate surface acoustic waves, which cause beam deflection and result in energy dissipation, this study uses FIDTs to concentrate the SAW energy based on structural features, resulting in better focusing performance and increased SAW amplitude. The experimental results reveal that the sensitivity of the structure is 1.51 µV/(°/s), and the bias instability is 0.77°/s, which are improved by an order of magnitude compared to those of a traditional SAW gyroscope. Thus, the FIDT component can enhance the performance of the SAW gyroscope, demonstrating its superiority for angular velocity measurements. This work provides new insights into improving the sensitivity and performance of SAW gyroscopes.

Preventing Subsidence Reoccurrence in Tianjin: New Preconsolidation Head and Safe Pumping Buffer.

Tianjin, a coastal metropolis in north China, has grappled with land subsidence for nearly a century. Yet, emerging evidence suggests a notable decrease in subsidence rates across Tianjin since 2019. This trend is primarily attributed to the importation of surface water from the Yangtze River system via the South-to-North Water Diversion Project, initiated in December 2014. Utilizing Sentinel-1A Interferometric Synthetic Aperture Radar (InSAR) data (2014-2023), this study reveals that one-third of the Tianjin plain has either halted subsidence or experienced land rebound. As a result, the deep aquifer system (~-200 to -450 m) beneath one third of the Tianjin plain has completed a consolidation cycle, leading to the establishment of new, locally specific preconsolidation heads. The identification of the newly established preconsolidation head seeks to answer a crucial question: How can we prevent the reoccurrence of subsidence in areas where it has already ceased? In essence, subsidence will stop when the local hydraulic head elevates to the new preconsolidation head (NPCH), and permanent subsidence will not be reinitiated as long as hydraulic head remains above the NPCH. The difference of the depth between current hydraulic head and the NPCH defines the safe pumping buffer (SPB). This study outlines detailed methods for identifying the NPCHs in the deep aquifer system from long-term InSAR and groundwater-level datasets. Determining NPCHs and ascertaining SPBs are crucial for estimating how much groundwater can be safely extracted without inducing permanent subsidence, and for developing sustainable strategies for long-term groundwater management and conservation.

Improving Clinical Outcomes: Hightibialosteotomy Plate Placement Combined with Arthroscopic Surgery.

Objective: Our study aimed to investigate the clinical efficacy of hightibialosteotomy (HTO) posterior plate placement combined with arthroscopic surgery for degenerative injury of the posterior horn of the medial meniscus with poor force lines in the lower extremity, improve joint function or relieve pain. Methods: The case data of 98 patients with osteoarthritis of the knee admitted to the Department of Orthopedics in our hospital from January 2019 to January 2023 were selected for retrospective analysis. The patients were divided into 54 patients, each in the study group and the comparison group according to the different treatment regimens. The study group received hightibialosteotomy plate placement combined with arthroscopic surgery, while the comparison group underwent hightibialosteotomy plate placement alone. The differences in knee scores, knee Lysholm scores, Lysholm scores, Healthcare Security and Safety (HSS) scores, Tegner scores, Visual Analog Scale (VAS), lower extremity force lines, femorotibial angles, and tibial plateau were counted and compared between the two groups. Results: HSS knee function scores, Lysholm scores, and VAS scores of the study group were statistically significant compared with those of the comparison group at the final follow-up of patients, and the postoperative clinical outcomes improved significantly (P < .05). The differences in Hip-Knee-Ankle(HKA) angle andMedial-Pateral Tibial Angle (MPTA) of patients in the study group were statistically significant compared with the comparison group, and the increase in HKA (12.31±2.13)°, MPTA (11.84±2.32)° and lower limb force line was significantly improved (P < .05). Preoperatively, there was no statistically significant comparison between the visual analog scores of the knee joint in the study group and the comparison group. After surgery, the difference between the two groups was statistically significant (P < .05). The relative position of the mechanical axis of the lower limb through the tibial plateau, the femorotibial angle, and the posterior tibial plateau angle increased in patients after surgery, and the differences were statistically significant when compared with the preoperative period (P < .05). Both the tibial posterior displacement distance and the lateral knee gap opening were reduced compared with the preoperative period, and the differences were statistically significant (P < .05). Conclusion: Hightibialosteotomy after plate placement combined with arthroscopic surgery has better clinical efficacy in the early stage and can effectively treat the degenerative injury of the posterior horn of the medial meniscus with poor force lines in the lower limb, improve the joint function, and relieve the symptoms of patients.

Genome-wide identification and comparative analysis of YABBY transcription factors in oil tea and tea tree.

The plant-specific transcription factor gene family, YABBY, plays an important role in plant development and stress response. Although YABBY genes have been identified in numerous species, a comprehensive characterization of YABBYs in tea tree and oil tea has been lacking. In this study, ten and three YABBY genes were identified in Camellia sinensis and C. oleifera, respectively. YABBY proteins could be divided into five subfamilies. Most YABBY genes in the same clade had similar structures and conserved motifs. Protein evolutionary analysis revealed that FIL/YAB3 displayed high conservation in all positions, followed by INO, YAB2, YAB5, and CRC. Specific site analysis suggested that the YABBY family was polyphyletic during the evolution. Compared to C. oleifera, two segmentally duplicated gene pairs were formed in C. sinensis during recent WGD events generated 30.69 and 45.08 Mya, respectively. Cis-acting element indicated that most YABBY genes contain box4, ARE, and MYB elements. A total of 120 SSR loci were found within CsYABBYs, consisting of six types, while 48 SSR loci were identified within CoYABBY, consisting of three types. Transcriptome results revealed that CRC and INO clades were specifically expressed in floral organs. The expression of CsYABBY10 and CsYABBY5 was significantly up-regulated under drought and salt treatments, respectively, as confirmed by qRT-PCR. CoYABBY genes were more susceptible to salt stress, as CoYABBY3 increased by about 15-fold. Furthermore, functional differentiation may have occurred in duplicated genes. These discoveries provide important information for further research on YABBYs in tea tree and oil tea. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03940-9.

Synergy of Spall Strength and Toughness in Nanograined Metals.

Under shock loading, the spall strength of nanocrystals exhibits intricate grain-size effects due to the presence of abundant grain boundary and dislocation activities. However, the influence of size on spall toughness and void evolution has been largely overlooked. This study employs molecular dynamics simulations to investigate the damage accumulation characteristics of nanocrystalline aluminum across various grain sizes. Unlike the trade-off observed in quasi-static loading conditions, our study reveals a consistency in which grain size governs both nanovoid nucleation and coalescence, yielding a novel spall strength-toughness synergy. These insights highlight grain sizes that are particularly susceptible to spall fracture, offering a crucial understanding of nanocrystal failure mechanisms in extreme environments.

Metabolic Patterns of Flavonoid and Its Key Gene Expression Characteristics of Five Cultivars of Tulipa gesneriana during Flower Development.

Flower color is one of the most important ornamental traits of tulips (Tulipa gesneriana). Five typical tulip cultivars were selected to identify the flavonoid components and analyze their key gene expression in their tepals. Firstly, after preliminary determination of the pigment type, the flavonoids were identified by UPLC-Q-TOF-MS. A total of 17 anthoxanthins were detected in the five cultivars. The total anthoxanthin content in the white tulip and the red tulip showed a similar decreasing trend, while an increasing trend was observed in the black tulip. Similarly, a total of 13 anthocyanins were detected in five tulip cultivars. The black tulip contained the largest number of anthocyanins, mainly delphinidin derivatives (Dp) and cyanidin derivatives (Cy). The total anthocyanin content (TAC) in the orange, red, and black cultivars was higher than that in the white and yellow cultivars and presented an overall increase trend along with the flower development. TgCHS, TgFLS, TgF3H, TgF3'H, TgF3'5'H, and TgDFR, as key structural genes, were involved in the flavonoid synthesis pathway, and the expression patterns of these genes are basically consistent with the components and accumulation patterns of flavonoids mentioned above. Taken together, the flower color in tulips was closely related to the composition and content of anthocyanins and anthoxanthins, which were indeed regulated by certain key structural genes in the flavonoid pathway.

A positive feedback between PDIA3P1 and OCT4 promotes the cancer stem cell properties of esophageal squamous cell carcinoma.

BACKGROUND: Increasing evidence has indicated that long non-coding RNAs (lncRNAs) have been proven to regulate esophageal cancer progression. The lncRNA protein disulfide isomerase family A member 3 pseudogene 1 (PDIA3P1) has been shown to promote cancer stem cell properties; however, its mechanism of action remains unclear. In this study, we investigated the regulation of esophageal cancer stem cell properties by the interaction of PDIA3P1 with proteins. METHODS: The GEPIA2 and Gene Expression Omnibus databases were used to analyze gene expression. PDIA3P1 expression in human esophageal squamous cell carcinoma (ESCC) tissues and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Loss-of-function experiments were performed to determine the effects of PDIA3P1 on ESCC cell proliferation, migration, and invasion. The sphere formation assay, number of side population cells, and CD271 + /CD44 + cells were detected by flow cytometry to identify the cancer stem cell properties. RNA immunoprecipitation (RIP), RNA pull-down, co-immunoprecipitation (co-IP), dual luciferase reporter, and cleavage under targets and tagmentation (CUT&Tag) assays were performed to elucidate the underlying molecular mechanisms. RESULTS: PDIA3P1 expression was upregulated in ESCC cell lines and tissues. Functionally, higher PDIA3P1 expression promoted cell proliferation, invasion, and metastasis and inhibited apoptosis in esophageal cancer. Importantly, PDIA3P1 promoted cancer stem cell properties in ESCC. Mechanistically, PDIA3P1 interacted with and stabilized octamer-binding transcription factor 4 (OCT4) by eliminating its ubiquitination by the ubiquitinating enzyme WW domain-containing protein 2 (WWP2). Moreover, as a transcription factor, OCT4 bound to the PDIA3P1 promoter and promoted its transcription. CONCLUSIONS: Our research revealed a novel mechanism by which a positive feedback loop exists between PDIA3P1 and OCT4. It also demonstrated that the PDIA3P1-WWP2-OCT4 loop is beneficial for promoting the cancer stem cell properties of ESCC. Owing to this regulatory relationship, the PDIA3P1-WWP2-OCT4-positive feedback loop might be used in the diagnosis and prognosis, as well as in the development of novel therapeutics for esophageal cancer.

CsCuAO1 Associated with CsAMADH1 Confers Drought Tolerance by Modulating GABA Levels in Tea Plants.

Our previous study showed that COPPER-CONTAINING AMINE OXIDASE (CuAO) and AMINOALDEHYDE DEHYDROGENASE (AMADH) could regulate the accumulation of γ-aminobutyric acid (GABA) in tea through the polyamine degradation pathway. However, their biological function in drought tolerance has not been determined. In this study, Camellia sinensis (Cs) CsCuAO1 associated with CsAMADH1 conferred drought tolerance, which modulated GABA levels in tea plants. The results showed that exogenous GABA spraying effectively alleviated the drought-induced physical damage. Arabidopsis lines overexpressing CsCuAO1 and CsAMADH1 exhibited enhanced resistance to drought, which promoted the synthesis of GABA and putrescine by stimulating reactive oxygen species' scavenging capacity and stomatal movement. However, the suppression of CsCuAO1 or CsAMADH1 in tea plants resulted in increased sensitivity to drought treatment. Moreover, co-overexpressing plants increased GABA accumulation both in an Agrobacterium-mediated Nicotiana benthamiana transient assay and transgenic Arabidopsis plants. In addition, a GABA transporter gene, CsGAT1, was identified, whose expression was strongly correlated with GABA accumulation levels in different tissues under drought stress. Taken together, CsCuAO1 and CsAMADH1 were involved in the response to drought stress through a dynamic GABA-putrescine balance. Our data will contribute to the characterization of GABA's biological functions in response to environmental stresses in plants.

Synthesis of NiFe-layered double hydroxides using triethanolamine-complexed precursors as oxygen evolution reaction catalysts: effects of Fe valence.

The synthesis of highly efficient NiFe-layered double hydroxides (NiFe-LDHs) to catalyze the oxygen evolution reaction (OER) is urgent and challenging. Herein, NiFe-FeCl3-x and NiFe-FeCl2-x samples (where FeCl3 and FeCl2 represent the Fe sources and x represents the imposed reaction time: 6, 12, and 24 h) were prepared via one-pot hydrothermal synthesis using Fe sources characterized by Fe(III) or Fe(II) valence states. In the presence of triethanolamine, when FeCl3 was used as the Fe source, pure NiFe-LDH was obtained, whose crystallinity increased with increasing hydrothermal treatment time. In contrast, when FeCl2 was used as the Fe source, a mixture of NiFe-LDH, Fe2O3, and trace amounts of Fe3O4 was obtained. The content of NiFe-LDH in the mixture increased under longer hydrothermal treatment and NiFe-FeCl3-x catalysts exhibited better OER performance than NiFe-FeCl2-x catalysts. Specifically, NiFe-FeCl3-6 afforded the highest OER performance with an overpotential of 246.8 mV at 10 mA cm-2 and a Tafel slope of 46.1 mV dec-1. Herein, we investigated the effects of the valence state of Fe precursors on the structures and OER activities of the prepared catalysts; the mechanism of NiFe-LDH formation via hydrothermal synthesis in the presence of triethanolamine was also proposed.

Factual and counterfactual learning in major adolescent depressive disorder, evidence from an instrumental learning study.

BACKGROUND: The incidence of adolescent depressive disorder is globally skyrocketing in recent decades, albeit the causes and the decision deficits depression incurs has yet to be well-examined. With an instrumental learning task, the aim of the current study is to investigate the extent to which learning behavior deviates from that observed in healthy adolescent controls and track the underlying mechanistic channel for such a deviation. METHODS: We recruited a group of adolescents with major depression and age-matched healthy control subjects to carry out the learning task with either gain or loss outcome and applied a reinforcement learning model that dissociates valence (positive v. negative) of reward prediction error and selection (chosen v. unchosen). RESULTS: The results demonstrated that adolescent depressive patients performed significantly less well than the control group. Learning rates suggested that the optimistic bias that overall characterizes healthy adolescent subjects was absent for the depressive adolescent patients. Moreover, depressed adolescents exhibited an increased pessimistic bias for the counterfactual outcome. Lastly, individual difference analysis suggested that these observed biases, which significantly deviated from that observed in normal controls, were linked with the severity of depressive symoptoms as measured by HAMD scores. CONCLUSIONS: By leveraging an incentivized instrumental learning task with computational modeling within a reinforcement learning framework, the current study reveals a mechanistic decision-making deficit in adolescent depressive disorder. These findings, which have implications for the identification of behavioral markers in depression, could support the clinical evaluation, including both diagnosis and prognosis of this disorder.