Robust, wide-range, and precise transmitter IQ impairment monitoring scheme for coherent digital subcarrier multiplexing systems.

In this Letter, we present a robust, wide-range, and precise monitoring scheme for transmitter (Tx) impairments in coherent digital subcarrier multiplexing (DSCM) systems. The proposed scheme employs frequency-domain pilot tones (FPTs) to compensate for frequency offset (FO), polarization aliasing, and carrier phase noise, thus isolating Tx impairments from channel distortions. It then implements 4 × 4 real-valued MIMO to compensate for Tx impairments by equalizing symmetric subcarriers. Tx impairment monitoring is derived from the equalizer coefficients. By considering the phase shift caused by Tx impairments, a wide-range and precise monitoring of Tx impairments including IQ skew, IQ phase, and gain imbalances is achieved. We experimentally validated our approach using a 48-GBaud, four-subcarrier, dual-polarization coherent DSCM system. The results confirm the method's capability for a wide-range, robust, and precise Tx impairment monitoring in coherent DSCM systems, maintaining performance even in the presence of ultra-fast polarization variation.

Robust, in-service, and joint monitoring of a dual-polarization transceiver IQ skew for a coherent DSCM system without channel impairment compensation.

A robust, in-service, and joint monitoring of a dual-polarization (DP) transceiver IQ skew for a coherent DSCM system is proposed and experimentally validated. Unlike traditional monitoring schemes, the proposed scheme realizes robust transceiver impairments monitoring without channel impairment compensation, including chromatic dispersion (CD), polarization variation, and carrier phase noise. This enhances the stability and precision of the monitoring process and reduces computational complexity by eliminating sophisticated DSP for impairment compensation. A complex system model for a single-tone signal is given first. Based on the model, the proposed scheme enables monitoring of the DP transmitter and the receiver IQ skew using the inserted frequency domain pilots (FPTs). Experimental results show that the proposed scheme can estimate the transceiver IQ skew within 16 ps with an estimation error of less than 0.2 ps and is robust to CD, polarization variation, phase noise, and amplified spontaneous emission noise. To the best of our knowledge, the proposed scheme achieves in-service transceiver IQ skew monitoring for coherent DSCM systems for the first time.

Construction and Properties of High-Toughness Soft-Soft Interfaces Based on the Adhesion of Natural Polyphenols.

Artificial joint replacement is the most effective way to treat osteoarthritis. However, these artificial joints are too stiff with high interfacial contact stress and poor surface lubrication, resulting in stress shielding and severe wear and tear lead to an extremely high failure rate. At present, hydrogels are considered the most promising substitute for artificial joint prostheses owing to their good biocompatibility, adjustable mechanical properties, and excellent flexibility. Nevertheless, a traditional single-layer hydrogel has poor bearing capacity and lubrication, which are far from the properties of natural articular cartilage. The high strength and low friction properties of natural articular cartilage are based on its own multilayer fibrous structure. Therefore, by simulating the multilayer structure of natural cartilage, a bilayer bionic cartilage hydrogel was prepared; that is, the upper hydrogel realized excellent lubrication and the lower hydrogel realized high load-bearing capacity. However, the interface binding of bilayer hydrogels is a challenge at present. Therefore, the interfacial adhesion of the bilayer hydrogel is improved by adding tannic acid (TA) based on the adhesion of the natural polyphenol structure. The average interfacial toughness reaches 3650 J/m2, and the average interfacial shear force reaches 800 kPa. In the preparation of the bilayer hydrogel, taking advantage of the coordination reaction between TA and metal cations, Fe3+ is further added to endow the bilayer hydrogel with excellent mechanical properties and good sliding friction performance. Therefore, this work opens up a new way to construct cartilage-like materials with high toughness and a soft-soft interface.

An in-Depth Exploration of the Genetic Interaction Network Between Ferroptosis and Acute Pancreatitis.

Background: Ferroptosis plays an important role in a variety of disease processes and is equally important in pancreatic diseases. However, the role of ferroptosis-related genes (FRGs) in acute pancreatitis (AP) remains unknown, and their specific potential mechanisms still need to be explored extensively. Methods: AP-related gene microarray data were obtained from the GEO database, while FRGs were obtained from the ferroptosis database (FerrDb). Differentially expressed genes (DEGs) were screened by the "limma" package, and GSEA was performed. The corresponding ferroptosis-related differentially expressed genes (FRDEGs) were screened, and GO and KEGG pathway analyses were performed. A PPI network was constructed to identify hub FRDEGs by CytoHubba, MCODE and CTD scores. Transcription factors and miRNAs predicted using the NetworkAnalyst database were used to establish the regulatory network. Immune cell infiltration analysis was performed by the R package "ssGSEA" algorithm. The hub genes were validated by transcriptome sequencing of AP model mice and immunohistochemistry in rats and mice. Results: A total of 82 FRDEGs were screened, and these genes were mainly associated with ferroptosis, hypoxic response, autophagy, mitophagy and immune inflammation. However, we also found that these genes are also jointly involved in other cell death modalities, such as apoptosis and necroptosis. Further analysis obtained 7 hub genes from 82 genes, and single-sample gene set enrichment analysis (ssGSEA) showed that the hub genes are closely associated with the infiltration of specific immune cells and the activation of immune pathways. Conclusion: This study reveals the complex functions and important roles of ferroptosis-related genes in AP and provides gene targets for further studies of AP.

The crosstalk between ferroptosis and mitochondrial dynamic regulatory networks.

Ferroptosis is an iron-driven cell death modality characterized by iron accumulation and excessive lipid peroxidation. Ferroptosis is closely related to mitochondrial function, as indicated by studies showing that mitochondrial dysfunction and damage promote oxidative stress, which in turn induces ferroptosis. Mitochondria play crucial roles in cellular homeostasis, and abnormalities in their morphology and function are closely associated with the development of many diseases. Mitochondria are highly dynamic organelles, and their stability is maintained through a series of regulatory pathways. Mitochondrial homeostasis is dynamically regulated, mainly via key processes such as mitochondrial fission, mitochondrial fusion and mitophagy; however, mitochondrial processes are prone to dysregulation. Mitochondrial fission and fusion and mitophagy are intimately related to ferroptosis. Therefore, investigations into the dynamic regulation of mitochondrial processes during ferroptosis are important to provide a better understanding of the development of disease. In this paper, we systematically summarized changes in ferroptosis, mitochondrial fission and fusion and mitophagy to promote an in-depth understanding of the mechanism underlying ferroptosis and provide a corresponding reference for the treatment of related diseases.

Identification of key microRNAs in exosomes derived from patients with the severe acute pancreatitis.

OBJECTIVE: Exosomes have been identified as important carriers of various genetic materials, including microRNAs (miRNAs). Increasing evidence indicates that the course of severe acute pancreatitis (SAP) is associated with miRNAs transported by exosomes. We aimed to identify the signature miRNAs as biomarkers of SAP. METHODS: We obtained exosomes from the SAP patients' blood. After separation, purification, and identification, we performed high-throughput sequencing and screened the differentially expressed(DE) miRNAs in the exosomes. Bioinformatics analysis was performed to identified the target genes of the miRNAs and the pathways enriched based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, and selected the key miRNAs related to SAP. Total RNA was extracted from patient serum exosomes to detect the expression levels of the selected miRNAs in exosomes of three experimental groups (mild -, moderately severe -, and severe AP) and a control group, using Real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: 272 DE miRNAs were identified between SAP and control group. Using bioinformatics analysis, we determined that the functions of the target genes were enriched in six signaling pathways including focal adhesion. Based on this, seven candidate signature miRNAs were selected: miR-603, miR-548ad-5p, miR-122-5p, miR-4477a, miR-192-5p, miR-215-5p, and miR-583. The RT-qPCR results of the seven miRNAs in the SAP group were consistent with the sequencing results. CONCLUSION: Exosome-derived miR-603, miR-548ad-5p, miR-122-5p, miR-4477a, miR-192-5p, miR-215-5p, miR-583 are positively correlated with SAP, which might provide new insights into the pathogenesis of SAP and serve as the biomarkers of SAP.

Prognostic biomarkers of pancreatic cancer identified based on a competing endogenous RNA regulatory network.

Background: Pancreatic cancer is an insidious and heterogeneous malignancy with poor prognosis that is often locally unresectable. Therefore, determining the underlying mechanisms and effective prognostic indicators of pancreatic cancer may help optimize clinical management. This study was conducted to develop a prognostic model for pancreatic cancer based on a competing endogenous RNA (ceRNA) network. Methods: We obtained transcriptomic data and corresponding clinicopathological information of pancreatic cancer samples from The Cancer Genome Atlas (TCGA) database (training set). Based on the ceRNA interaction network, we screened candidate genes to build prediction models. Univariate Cox regression analysis was performed to screen for genes associated with prognosis, and least absolute shrinkage and selection operator (LASSO) regression analysis was conducted to construct a predictive model. A receiver operating characteristic (ROC) curve was drawn, and the C-index was calculated to evaluate the accuracy of the prediction model. Furthermore, we downloaded transcriptomic data and related clinical information of pancreatic cancer samples from the Gene Expression Omnibus database (validation set) to evaluate the robustness of our prediction model. Results: Eight genes (ANLN, FHDC1, LY6D, SMAD6, ACKR4, RAB27B, AUNIP, and GPRIN3) were used to construct the prediction model, which was confirmed as an independent predictor for evaluating the prognosis of patients with pancreatic cancer through univariate and multivariate Cox regression analysis. By plotting the decision curve, we found that the risk score model is an independent predictor has the greatest impact on survival compared to pathological stage and targeted molecular therapy. Conclusions: An eight-gene prediction model was constructed for effectively and independently predicting the prognosis of patients with pancreatic cancer. These eight genes identified show potential as diagnostic and therapeutic targets.

Homocysteine promotes migration of adventitial fibroblasts via angiotensin II type 1 receptor activation to aggravate atherosclerosis.

This study clarified the effect of homocysteine on adventitial fibroblasts (AFs) and its relationship with angiotensin II type 1 receptor (AT1R). Hyperhomocysteinemia aggravated the plaque area and increased the expression of IL-6, MCP-1, and macrophage infiltration in the plaque and adventitia of the aorta, whereas telmisartan improved this effect. Hyperhomocysteinemia induced the occurrence of the AFs marker protein ER-TR7 in the plaque and entire layer of the aorta, whereas telmisartan improved these effects, indicating that homocysteine induced AFs migration and that AT1R mediated this process. The migration experiments of AFs also reached the same conclusion. Homocysteine increased the phosphorylation levels of PKC and ERK1/2 in the AFs and HEK293A cells transfected with the AT1R plasmid, whereas telmisartan inhibited this effect, indicating that homocysteine activated AT1R intracellular signaling pathway. Homocysteine also increased the AFs At1R expression. Conclusion, homocysteine promoted adventitial inflammation, induced AFs migration, and aggravated atherosclerosis by activating AT1R.

Microclimate environment model construction and control strategy of enclosed laying brooder house.

The growth performance and health of chicks can be significantly improved by a suitable microclimate in brooder houses. However, the microclimate of the chicken house is affected by factors such as its structure and the heat dissipation of chickens, making it is difficult to establish an accurate mathematical model and achieve effective regulation. In this paper, the environmental data acquisition system of enclosed chick brooder house was established by analyzing various environmental factors in brooder houses. According to the structural characteristics of brooder houses and the growth environment of chicks and other parameters, the microclimate simulation model of brooder houses was established using the physical law of energy balance. The coefficient of determination R2 (R-square) between simulated temperature and humidity output value and measured value was 0.7634 and 0.9740, respectively, and Root Mean Square Error (RMSE) was 1.55°C and 2.61%, respectively. The correctness of the simulation model was verified. On the basis of established microclimate models, a simulation model of fuzzy decoupling Proportion Integration Differentiation (PID) control in chicken house environments was established for the strong coupling between temperature control and general risk control system in chicken houses. Different control strategies were generated by fuzzy and logical reasoning about multiple environmental factors. The compensation coefficient was added to optimize the environmental regulation system of brooder houses. The temperature maximum deviation between the set value and the fuzzy decoupling PID controller was 0.5°C, the maximum relative error was 2.7%, the maximum deviation of relative humidity between the set value and the fuzzy decoupling PID controller was 4.93%, the maximum relative error was 10.49%.The simulation results show the control strategy meets the temperature and humidity control requirements, verify the effectiveness of the control strategy and model. The experimental results can guide the actual environmental control of brooder houses.

Large-aperture single-mode 795 nm VCSEL for chip-scale nuclear magnetic resonance gyroscope with an output power of 4.1 mW at 80 °C.

Transverse optical confinement in oxide-confined vertical-cavity surface-emitting lasers (VCSELs) crucially depends on thickness of oxide layer and its position relative to a standing wave. Modifying the structure reduces the overlap between the oxide layer and the standing wave as well as effective refractive index difference between core and cladding of the VCSEL that subsequently decreases of the number of transverse modes and increases the mode extension beyond oxide aperture. A 795 nm VCSEL is designed and fabricated with this concept. The proposed device achieves high single-mode operation of 4.1 mW at 80 °C, SMSR of 41.68 dB, and OPSR of 27.4 dB. VCSEL is applied in a nuclear magnetic resonance gyroscope (NMRG) system as pump source due to its excellent device performance and satisfactory test results are obtained.

Dimethyl Fumarate Combined With Vemurafenib Enhances Anti-Melanoma Efficacy via Inhibiting the Hippo/YAP, NRF2-ARE, and AKT/mTOR/ERK Pathways in A375 Melanoma Cells.

Melanoma is a deadly form of skin cancer with high rates of resistance to traditional chemotherapy and radiotherapy. BRAF inhibitors (BRAFi) can achieve initial efficacy when used to treat melanoma patients, but drug resistance and relapse are common, emphasizing the need for new therapeutic strategies. Herein, we reported that combination of dimethyl fumarate (DMF) and vemurafenib (Vem) inhibited melanoma cell proliferation more significantly and induced more cell death than single agent did both in vitro and in vivo. DMF/Vem treatment induced cell death through inhibiting the expression and transcriptional activity of NRF2 thereby resulting in more reactive oxygen species (ROS) and via inhibiting the expression of YAP, a key downstream effector of Hippo pathway. DMF/Vem treatment also reduced phosphorylation of AKT, 4EBP1, P70S6K and ERK in AKT/mTOR/ERK signaling pathways. RNA-seq analysis revealed that DMF/Vem treatment specifically suppressed 4561 genes which belong to dozens of cell signaling pathways. These results indicated that DMF/Vem treatment manifested an enhanced antitumor efficacy through inhibiting multiple cell signaling pathways, and thus would be a novel promising therapeutic approach targeted for melanoma.

Investigation on the antitumor effects of paeonol against renal cell carcinoma based on network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Renal cell carcinoma (RCC) is the most common cancer of the urinary system, the current treatments for RCC are unsatisfactory. Paeonol is the main pharmacologically active ingredient of the traditional Chinese medicine (TCM) moutan cortex (Paeonia suffruticosa Andrews) and Paeonia albiflora Pall, and has been used in TCM to treat various diseases including cancer. However, the underlying therapeutic mechanisms of paeonol in RCC have not been investigated yet. AIM OF THE STUDY: This study aimed to explore the potential antitumor effects and mechanisms of paeonol on RCC based on network pharmacology and experimental validation. MATERIALS AND METHODS: Network pharmacological analysis was performed to predict the potential targets and mechanism of paeonol against RCC. The antitumor effects and the priority targets of paeonol against RCC were further assessed by in vitro experiments. RESULTS: 104 intersection targets shared by paeonol and RCC were collected, 15 hub genes were obtained, among these genes, VEGFA expression was higher in RCC, and the higher expression of IL-6 or lower expression of AKT1, JUN, MAPK1, and MAPK8 were correlated to the shorter overall survival (OS) in RCC patients. GO and KEGG analyses suggested that the genes were mainly enriched in the positive regulation of cell death and apoptosis pathway. In vitro experiments showed that paeonol inhibited 786-O cell proliferation, migration, invasion, and promoted apoptosis. When 786-O cells were treated with paeonol, the expression of Bax increased while Bcl-2 and VEGFA decreased. CONCLUSION: The present study demonstrated that paeonol might play an essential role in RCC by regulating cell proliferation, apoptosis, metastasis, and invasion through the Bcl-2/Bax signaling pathway and VEGFA, providing a theoretical and experimental scientific basis for future investigations of the antitumor effects of paeonol against RCC.

Comprehensive evaluation method of the poultry house indoor environment based on gray relation analysis and analytic hierarchy process.

Due to the antagonism and synergy among environmental factors in the poultry house, the influence process becomes extremely complex. As a result, it is difficult to predict and evaluate the degree of such influence accurately. In this paper, we study the poultry house environment factor and its relationship with poultry production performance, using the gray relation analysis (GRA) to filtrate the main factors that influence the evaluation of the poultry house environment. Put forward using the gray relation degree (GRD) to improve the method for structuring the judgment matrix, and weights are more objective and reasonable. The evaluation index system and evaluation model are constructed through the analytic hierarchy process (AHP). It is expected that the comprehensive evaluation of the indoor environment status of the poultry house can guide the optimization of the environmental control in the poultry house and obtain better production indicators of the poultry. In this study, the experimental broiler house was enclosed in autumn. Because of the ventilation system, the indoor environment is still affected by the outdoor environment. The top 3 in the calculation of weights were outdoor environment (0.4315), indoor temperature (0.2384), and indoor air quality (0.1687), which were consistent with experience. From October 24 to 27, the environmental evaluation values of the experimental broiler house were {2.4367, 2.8149, 2.3857, 2.5669}, that is, the evaluation results were {good, good, good, good}; consistent with the expert manual judgment. The correctness and practicability of the proposed method were verified. This paper provides a scientific basis for environmental evaluation and environmental control in the poultry house.

Anterior abdominal abscess - a rare manifestation of severe acute pancreatitis: A case report.

BACKGROUND: Severe acute pancreatitis (SAP) is a common critical disease of the digestive system. In addition to the clinical manifestations and biochemical changes of acute pancreatitis, SAP is also accompanied by organ failure lasting more than 48 h. SAP is characterized by focal or extensive pancreatic necrosis, hemorrhage and obvious inflammation around the pancreas. The peripancreatic fat space, fascia, mesentery and adjacent organs are often involved. The common local complications include acute peripancreatic fluid collection, acute necrotic collection, pancreatic pseudocyst, walled off necrosis and infected pancreatic necrosis. After reviewing the literature, we found that in very few cases, SAP patients have complications with anterior abdominal wall abscesses. CASE SUMMARY: We report a 66-year-old Asian male with severe acute pancreatitis who presented with intermittent abdominal pain and an increasing abdominal mass. The abscess spread from the retroperitoneum to the anterior abdominal wall and the right groin. In the described case, drainage tubes were placed in the retroperitoneal and anterior abdominal wall by percutaneous puncture. After a series of symptomatic supportive therapies, the patient was discharged from the hospital with a retroperitoneal drainage tube after the toleration of oral feeding and the improvement of nutritional status. CONCLUSION: We believe that patients with SAP complicated with anterior abdominal abscess can be treated conservatively to avoid unnecessary exploration or operation.

Exosomes secreted from human umbilical cord mesenchymal stem cells promote pancreatic ductal adenocarcinoma growth by transferring miR-100-5p.

PURPOSE: Although human umbilical cord mesenchymal stem cells (hucMSCs) can contribute to the growth of tumors, including pancreatic ductal adenocarcinoma (PDAC), however, little is known about the exact mechanisms by which the exosomes secreted from hucMSCs (hucMSCs-exo) have an oncogenic effect on the physiopathology of PDAC. The effects of hucMSCs on tumor development are attributed to hucMSCs-exo, which deliver unique proteins and miRNAs to cancer cells. METHODS: HucMSCs and exosomes were isolated and confirmed via transmission electron microscopy, nanoparticle tracking analysis and western blot. The nude mice were inoculated subcutaneously on both flanks with human pancreatic cancer Panc-1 cells (1 × 106), and hucMSCs-exo were directly administered via intratumoral injection once a day for three days each week. Cell proliferation assays were performed using a Cell Counting Kit-8 assay and the cell invasion assay was performed using Transwell assay. The miRNA data were predicted and analyzed by miRanda software. The analysis of the target genes of the miRNAs was proformed with the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. RESULTS: Firstly, we observed that hucMSCs-exo promoted Panc-1 and BxPC3 cell growth by increasing proliferation and migration in vitro. Secondly, in a xenograft tumor model, hucMSCs-exo increased the growth of Panc-1 cells. Thirdly, high-throughput sequencing of hucMSCs-exo showed that hsa-miR-148a-3p, hsa-miR-100-5p, hsa-miR-143-3p, hsa-miR-21-5p and hsa-miR-92a-3p were highly expressed. For the five identified miRNAs, 1308 target genes were predicted by miRanda software. From the GO and KEGG analyses of the target genes of the identified miRNAs, it was found that the main GO function was the regulation of cellular glucuronidation, and the main KEGG metabolic pathway involved the metabolism of ascorbic acid and aldehyde acid. These processes are related to the occurrence and development of pancreatic cancer. Finally, we observed that miR-100-5p promoted Panc-1 and BxPC3 cell growth in vitro and in vivo. CONCLUSION: Here, by utilizing exosomes secreted from hucMSCs, we systematically investigated the effects of hucMSCs-exo on PDAC growth in vitro and in vivo for the first time. Building on these results, we provided new insights into the role of hucMSCs-exo in the PDAC growth and revealed the attractive communication between hucMSCs and PDAC cells that occurs through MSCs-exosomes-miRNAs.

Dynamics of carbon stocks of different pools in Huzhong National Nature Reserve, Northeast China under the disturbance of various severity fires.

In this study, the FireBGCv2 model was used to simulate the dynamics of forest carbon pools of Huzhong Nature Reserve within the next 100 years under various forest fire severity scena-rios. The aim of this study was to explore the responses of different forest carbon pools to fire disturbance, and to provide scientific basis for forest fuel management. The results showed that forest fire significantly reduced forest carbon storage, with the greatest reduction under the scenario of high-severity forest fire. Fire disturbance affected carbon storage in different pools, and relocated carbon among those pools. Forest fire disturbance reduced carbon storage of living trees and duff, increased that of coarse woody debris in the early and middle stages of simulation, and decreased that in late stage. The carbon storage of shrub and herb strata increased significantly in the late simulation period. The higher the fire severity, the lower the carbon storage of living tree and shrub-herb carbon pools, with snag and coarse woody debris showing the opposite trend. The impact of forest fire disturbance on the total carbon pool distribution was as follows: forest fire increased the proportion of shrub and herb strata, snag, coarse woody debris and soil carbon pool, and reduced the proportion of living tree and duff. The higher severity forest fire was, the lower the proportion of carbon pool of shrub-herb, and the higher the proportion of carbon pool of coarse wood debris. The severity of forest fire had less impact on the proportion of other carbon pools. In addition, our results demonstrated periodic change of litter carbon that reached a high value within 20 years and then dropped to a low value within 10 years. Our results could provide sound basis for determining the forest fuel treatment interval. We suggested performing prescribed burning every 20 years in the Great Xing'an Mountains area to protect forest resources.

Zhenbao pill attenuates hydrogen peroxide-induced apoptosis by inhibiting autophagy in human umbilical vein endothelial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: The Zhenbao pill (ZBP) is composed of 29 traditional Chinese medicines and has been proven to exhibit a valid therapeutic effect in nervous system diseases, such as stroke and hemiplegia sequelae. AIM OF THE STUDY: Whether ZBP has a protective effect on vascular endothelial cells remains unknown. In this study, we established hydrogen peroxide (H2O2)-induced oxidative injury in human umbilical vein endothelial cells (HUVECs) as an in vitro model to investigate the pharmacological effects of ZBP. MATERIALS AND METHODS: Following the intragastric administration of ZBP (0.25, 0.5, and 1 g/kg for seven days) in rats, drug-containing serum was obtained and cultivated with HUVECs before H2O2 treatment. The viability of HUVECs in the presence of H2O2 was measured by Cell Counting Kit-8 assay, lactate dehydrogenase assay, and flow cytometry. Furthermore, we estimated the effects of ZBP on the production of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP). Autophagic puncta were detected using a fluorescence microscope. Western blotting and real-time polymerase chain reaction were used to detect the expression levels of several genes associated with apoptosis and autophagy. RESULTS: Drug-containing serum separated from rats at 1 h after intragastric administration of ZBP (0.5 g/kg) significantly offered a protective effect to HUVECs and reduced cell apoptosis rates. Meanwhile, ZBP-containing serum also repressed ROS production induced by H2O2 exposure and maintained MMP. Further investigation revealed that ZBP-containing serum effectively reduced the accumulation of autophagic puncta. ZBP-mediated inhibition on cell autophagy was found to contribute to ameliorating cell apoptosis. Western blotting also confirmed that ZBP maintained AKT and mTOR phosphorylation and antagonized the imbalance of BCL2/BAX, thereby protecting cells from apoptosis. CONCLUSION: Taken together, our data indicate that ZBP inhibits ROS production, mitochondrial damage, cell autophagy, and cell apoptosis. ZBP can offer protection to vascular endothelial cells against oxidative injury through the antagonism of apoptosis and autophagy. Thus, this study enhances the understanding of the therapeutic effects and mechanisms of ZBP in the process of recovery from myocardial and cerebral ischemic stroke.

Extracellular vesicles and pancreatitis: mechanisms, status and perspectives.

Comprehensive reviews and large population-based cohort studies have played an important role in the diagnosis and treatment of pancreatitis and its sequelae. The incidence and mortality of pancreatitis have been reduced significantly due to substantial advancements in the pathophysiological mechanisms and clinically effective treatments. The study of extracellular vesicles (EVs) has the potential to identify cell-to-cell communication in diseases such as pancreatitis. Exosomes are a subset of EVs with an average diameter of 50~150 nm. Their diverse and unique constituents include nucleic acids, proteins, and lipids, which can be transferred to trigger phenotypic changes of recipient cells. In recent years, many reports have indicated the role of EVs in pancreatitis, including acute pancreatitis, chronic pancreatitis and autoimmune pancreatitis, suggesting their potential influence on the development and progression of pancreatitis. Plasma exosomes of acute pancreatitis can effectively reach the alveolar cavity and activate alveolar macrophages to cause acute lung injury. Furthermore, upregulated exosomal miRNAs can be used as biomarkers for acute pancreatitis. Here, we summarized the current understanding of EVs in pancreatitis with an emphasis on their biological roles and their potential use as diagnostic biomarkers and therapeutic agents for this disease.

Head and body/tail pancreatic neuroendocrine tumors have different biological characteristics and clinical outcomes.

PURPOSE: The incidence of pancreatic neuroendocrine tumors (pNETs) has continued to increase, but for pNETs, there is still no distinction between treatments based on anatomical location. We aim to determine whether NETs located at the head and body/tail of the pancreas are different. PATIENTS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2016), we focused on pNETs patients with comprehensive information. The patients were divided into two groups based on tumors' location. We compared the characteristics of the two groups and assessed the risk factors for lymphatic metastasis. Survival analysis was performed based on the biological characteristics of the tumor. RESULTS: In all 3011 patients, pNETs were more common in the body/tail (62.94%) than in the head (37.06%) of the pancreas. The risk factors for lymph node metastasis in the two groups were different. Nonmetastatic, low-grade pancreatic body/tail NETs had the best prognosis (p < 0.001). For low-grade tumors (G1-G2), lymphatic metastasis did not significantly affect the prognosis of patients with pancreatic head NETs (p = 0.098) but affected the overall survival of patients with pancreatic body/tail NETs (p < 0.001). The tumors at the pancreatic head were larger (p = 0.001), more likely to have positive lymph nodes (p < 0.001) and more prone to locally advanced and distant invasion (p < 0.001). The prognosis of pancreatic head NETs 21-40 mm was worse than that of body/tail pNETs (p < 0.001). For non-functional NETs, the overall survival of pancreatic body/tail tumors was better (p < 0.001). CONCLUSION: The pancreatic head and pancreatic body/tail NETs have different biological characteristics and clinical outcomes and they should be treated differently.

Characterization of Endothelial Cells Associated with Cerebral Arteriovenous Malformation.

INTRODUCTION: Cerebral arteriovenous malformation (cAVM) is a disease characterized by the angiogenesis and remodeling of veins. However, whether vascular endothelial cells (ECs) exhibit morphological and functional changes during cAVM remains unclear. This study aimed to investigate the role of ECs in the pathogenesis of cAVM. METHODS: Rat model of cAVM was established by anastomosing the common carotid artery with the external jugular vein. The digital subtraction angiography (DSA), HE, Masson and immunohistochemical staining were performed to evaluate the model. ECs were isolated from AVM rat model or control rats, and characterized by MTT, cell scratch, and tube formation assays. The secretion of vascular endothelial growth factor (VEGF) was detected by ELISA. RESULTS: AVM rat model showed typical pathological characteristics of cAVM. In addition, the proliferation, migration and tube formation abilities of ECs of arterialized vein (AV-ECs) were significantly better than those of ECs of normal vein (NV-ECs). Moreover, the levels of secreted VEGF were significantly higher in AV-ECs than in NV-ECs. CONCLUSION: AV-ECs isolated from AVM rat model showed increased proliferation, migration and angiogenesis and may be potential target for the treatment of cAVM.