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Xiaoyin Bu,1,2,* Weifeng Pan,1,* Junhui Wang,1 Liping Liu,1 Zhao Yin,1 Hua Jin,1 Qifa Liu,1 Lei Zheng,3 Haitao Sun,4 Ya Gao,3 Baohong Ping1,2 1Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Department of Hematology, Huiqiao Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 3Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 4Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, People’s Republic of China*These authors contributed equally to this workCorrespondence: Baohong Ping, Department of Hematology, Huiqiao Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China, Tel +86 15625042109, Fax +86 2062781875, Email nfyypingbaohong66@163.com Ya Gao, Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China, Email smugaoya_729@163.comBackground: Acute graft-versus-host disease (aGVHD) initiated by intestinal barrier dysfunction and gut microbiota dysbiosis, remains one of the main obstacles for patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) to achieve good prognosis. Studies have suggested that mesenchymal stem cells (MSCs) can suppress immune responses and reduce inflammation, and human leukocyte antigen-G5 (HLA-G5) plays an important role in the immunomodulatory effects of MSCs, but very little is known about the potential mechanisms in aGVHD. Thus, we explored the effect of HLA-G5 on the immunosuppressive properties of human amnion MSCs (hAMSCs) and demonstrated its mechanism related to the gut microbiota at the intestinal barrier in aGVHD.Methods: Patients undergoing allo-HSCT were enrolled to detect the levels of plasma-soluble HLA-G (sHLA-G) and regulatory T cells (Tregs). Humanized aGVHD mouse models were established and treated with hAMSCs or HLA-G5 overexpressing hAMSCs (ov-HLA-G5-hAMSCs) to explore the mechanism of HLA-G5 mediated immunosuppressive properties of hAMSCs and the effect of ov-HLA-G5-hAMSCs on the gut microbiota at the intestinal barrier in aGVHD.Results: The plasma levels of sHLA-G on day +30 after allo-HSCT in aGVHD patients were lower than those in patients without aGVHD, and the sHLA-G levels were positively correlated with Tregs percentages. ov-HLA-G5-hAMSCs had the potential to inhibit the expansion of CD3+CD4+ T and CD3+CD8+ T cells and promote Tregs differentiation, suppress proinflammatory cytokine secretion but promote anti-inflammatory cytokines release. Besides, ov-HLA-G5-hAMSCs also could reverse the intestinal barrier dysfunction and gut microbiota dysbiosis in aGVHD.Conclusion: We demonstrated that HLA-G might work with Tregs to create a regulatory network together to reduce the occurrence of aGVHD. HLA-G5 mediated hAMSCs to exert higher immunosuppressive properties in vivo and reverse the immune imbalance caused by T lymphocytes and cytokines. Furthermore, HLA-G5 overexpressing hAMSCs could restore gut microbiota and intestinal barriers, thereby ameliorating aGVHD.Keywords: acute graft-versus-host disease, amniotic mesenchymal stem cells, human leukocyte antigen-G5, gut microbiota, intestinal barrier

Ya Gao,1,* Weiru Li,1,* Xiaoyin Bu,1,* Ying Xu,1 Shengchun Cai,1 Jinman Zhong,1 Meixue Du,1 Haitao Sun,2 Liping Huang,3 Yongjian He,4 Xiumei Hu,4 Qifa Liu,1 Hua Jin,1 Qian Wang,2,4 Baohong Ping5 1Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, People’s Republic of China; 3Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 4Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 5Department of Hematology, Huiqiao Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China*These authors contributed equally to this workCorrespondence: Baohong PingDepartment of Hematology, Huiqiao Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of ChinaTel +8615625042109Fax +862061642231Email nfyypingbaohong66@163.comQian WangDepartment of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of ChinaTel +8613822251298Fax +862061643018Email wangqian@smu.edu.cnBackground: Acute graft versus host disease (aGVHD) remains a leading cause of transplant-related mortality following allogeneic haematopoietic cell transplantation (allo-HCT). Human amniotic mesenchymal stem cells (hAMSCs) are a novel mesenchymal stem cells (MSCs), which have stronger proliferation and immunomodulatory ability compared with bone marrow mesenchymal stem cells (BM-MSCs). Besides, as the amniotic membrane is often treated as medical waste after delivery, hAMSCs can be obtained conveniently and noninvasively. The aim of this study was to explore the therapeutic efficacy and underlying mechanisms of hAMSCs transplantation for the humanized aGVHD mouse model.Methods: We established a humanized aGVHD mouse model by transplanting human peripheral blood mononuclear cells (PBMCs) into NOD-PrkdcscidIL2rγnull (NPG) mice, human amniotic membrane collected from discarded placenta of healthy pregnant women after delivery and hAMSCs were extracted from amniotic membrane and expanded in vitro. Mice were divided into untreated group (Control), aGVHD group (aGVHD), and hAMSCs treatment group (aGVHD+hAMSCs), the hAMSCs labeled with GFP were administered to aGVHD mice to explore the homing ability of hAMSCs. T effector and regulatory T cells (Tregs) levels and cytokines of each group in target organs were detected by flow cytometry and cytometric bead array (CBA), respectively.Results: We successfully established a humanized aGVHD mouse model using NPG mice. The hAMSCs have the ability to inhibit aGVHD in this mouse model through reduced villous blunting and lymphocyte infiltration of the gut while reducing inflammatory edema, tissue destruction and lymphocyte infiltration into the parenchyma of the liver and lung. hAMSCs suppressed CD3+CD4+ T and CD3+CD8+ T cell expression and increased the proportion of Tregs, and besides, hAMSCs can reduce the levels of IL-17A, INF-γ, and TNF in aGVHD target organs.Conclusion: The NPG murine environment was capable of activating human T cells to produce aGVHD pathology to mimic aGVHD as in humans. The hAMSCs controlled aGVHD by decreasing inflammatory cytokine secretion within target organs by modulating the balance of Tregs and T effector cells in humanized mice.Keywords: acute graft versus host disease, humanized mouse model, NPG mice, amniotic mesenchymal stem cells, immunomodulatory

Trimethylamine oxide (TMAO) is a microbiota-derived metabolite, and numerous studies have shown that it could regulate fat metabolism in humans and mice. However, few studies have focused on the effects of TMAO on fat deposition in growing-finishing pigs. This study aimed to investigate the effect of TMAO on fat deposition and intestinal microbiota in growing-finishing pigs. Sixteen growing pigs were randomly divided into 2 groups and fed with a basal diet with 0 or 1 g/kg TMAO for 149 d. The intestinal microbial profiles, fat deposition indexes, and fatty acid profiles were measured. These results showed that TMAO supplementation had a tendency to decrease lean body mass (P

Abstract Targeting receptor‐interacting protein kinase 1 (RIPK1) has emerged as a promising therapeutic stratagem for neurodegenerative disorders, particularly Alzheimer's disease (AD). A positron emission tomography (PET) probe enabling brain RIPK1 imaging can provide a powerful tool to unveil the neuropathology associated with RIPK1. Herein, the development of a new PET radioligand, [11C]CNY‐10 is reported, which may enable brain RIPK1 imaging. [11C]CNY‐10 is radiosynthesized with a high radiochemical yield (41.8%) and molar activity (305 GBq/µmol). [11C]CNY‐10 is characterized by PET imaging in rodents and a non‐human primate, demonstrating good brain penetration, binding specificity, and a suitable clearance kinetic profile. It is performed autoradiography of [11C]CNY‐10 in human AD and healthy control postmortem brain tissues, which shows strong radiosignal in AD brains higher than healthy controls. Subsequently, it is conducted further characterization of RIPK1 in AD using [11C]CNY‐10‐based PET studies in combination with immunohistochemistry leveraging the 5xFAD mouse model. It is found that AD mice revealed RIPK1 brain signal significantly higher than WT control mice and that RIPK1 is closely related to amyloid plaques in the brain. The studies enable further translational studies of [11C]CNY‐10 for AD and potentially other RIPK1‐related human studies.

Kidney diseases are significant global public health concern, with increasing prevalence and substantial economic impact. Developing novel therapeutic approaches are essential for delaying disease progression and improving patient quality of life. Cell death signifying the termination of cellular life, could facilitate appropriate bodily development and internal homeostasis. Recently, regulated cell death (RCD) forms such as ferroptosis, characterized by iron-dependent lipid peroxidation, has garnered attention in diverse renal diseases and other pathological conditions. This review offers a comprehensive examination of ferroptosis, encompassing an analysis of the involvement of iron and lipid metabolism, the System Xc-/glutathione/glutathione peroxidase 4 signaling, and additional associated pathways. Meanwhile, the review delves into the potential of targeting ferroptosis as a therapeutic approach in the management of acute kidney injury (AKI), chronic kidney disease (CKD), diabetic nephropathy, and renal tumors. Furthermore, it emphasizes the significance of ferroptosis in the transition from AKI to CKD and further accentuates the potential for repurposing drug and utilizing traditional medicine in targeting ferroptosis-related pathways for clinical applications. The integrated review provides valuable insights into the role of ferroptosis in kidney diseases and highlights the potential for targeting ferroptosis as a therapeutic strategy.

The Unmanned Aerial Vehicle (UAV) sprayer has the advantages of high work efficiency, simple operation, and high safety factor, and has broad application prospects UAV sprayer are widely used in the agricultural field, and the application of UAV sprayer spraying technology in agriculture has provided convenience and increased profits for farmers, and has also become a research hotspot in the field of agriculture. In recent years, although research has been conducted on the feasibility and application effects of UAV sprayer spraying crown shaped plants, there have been no experiments or studies in the field of garden plants. This experiment conducted a droplet deposition experiment of UAV sprayer spraying garden plants, exploring the droplet deposition effect of UAV sprayer in the field of garden plants, and conducting experiments on the influence of spray volume and nozzle type on droplet deposition. The experimental results showed that the canopy performance of small and medium-sized garden plants was better at a flight altitude of 1.5m, a spray volume of 180L/hm2, and a flight speed of 2m/s. Reducing flight altitude, increasing spray volume, and reducing flight speed can improve the distribution of droplets in the canopy. This experiment lays the foundation for the application of UAV sprayer for the prevention and control of pests and diseases in garden plants, as well as for the application of growth regulators, and provides a basis for further innovative research in the field of garden plant application technology.

In the paper, the autoregressive moving average model for matrix time series (MARMA) is investigated. The properties of the MARMA model are investigated by using the conditional least square estimation, the conditional maximum likelihood estimation, the projection theorem in Hilbert space and the decomposition technique of time series, which include necessary and sufficient conditions for stationarity and invertibility, model parameter estimation, model testing and model forecasting.

Abstract Background Takayasu arteritis (TAK) is a chronic inflammatory arteritis. It most often affects non-specific large vessel progressively, such as the aorta and its branches. The diagnosis in TAK is typically delayed. Isolated pulmonary artery involvement in Takayasu arteritis is uncommon. Owing to its rarity, the diagnosis is challenging and requires an integrated approach comprising clinical and imaging findings. In order to facilitate early diagnosis of TAK for clinicians, wider use of non-invasive imaging is impacting this. Case presentation In this report, we present the imaging characteristics of a rare isolated pulmonary artery involvement in Takayasu arteritis. Pulmonary computed tomography angiography revealed only limited thick walls of both proximal pulmonary artery and stenosis of pulmonary artery lumen, and the other large blood vessels were not involved. The patient undergone pulmonary endarterectomy and pulmonary angioplasty. Then, approximately one month afterward, she passed away due to heart failure. Conclusions Imaging examination is the main basis for diagnosing this disease. This impression might improve disease awareness among doctors and progress in diagnosis.

Abstract Background Although colonoscopy is the standard screening test for colorectal cancer (CRC), its use is limited by a poor compliance rate, the need for extensive bowel preparation, and the risk of complications. As an alternative, an FDA-approved stool-based DNA test, Cologuard, has demonstrated satisfactory detection performance for CRC, but its compliance rate remains suboptimal, primarily attributable to individuals’ reluctance to provide stool samples. Methods We developed a noninvasive blood-based CRC test, ColonSecure, based on cell-free DNA containing cancer-specific CpG island methylation patterns. We initially screened publicly available datasets for differentially methylated CpG sites in CRC with prediction potential. Subsequently, we performed two sequential bisulfite-free methylation sequencing on blood samples obtained from CRC patients and non-cancer controls. Through rigorous evaluation of each marker and machine learning-assisted feature selection, we identified 149 hypermethylated markers from over 193,000 CpG sites. These markers were then utilized to construct the ColonSecure model, enabling accurate CRC detection. Results We validated the efficacy of our cell-free DNA methylation-based blood test for CRC screening with 3493 high-risk individuals identified from 114,136 urban residents. The ColonSecure test identified 89 out of 103 CRC patients diagnosed by the follow-up colonoscopy, outperforming CEA, CRP, and CA19-9 (with a sensitivity of 86.4% compared to 45.6%, 39.8%, and 25.2% for CEA, CRP, and CA19-9 respectively; an AUROC of 0.956 compared to an AUROC of

Dielectric optical antennas have emerged as a promising nanophotonic architecture for manipulating the propagation and localization of light. However, the optically induced Mie resonances in an isolated nanoantenna are normally with broad spectra and poor Q-factors, limiting their performances in sensing, lasing, and nonlinear optics. Here, we dramatically enhance the Q-factors of Mie resonances in silicon (Si) nanoparticles across the optical band by arranging the nanoparticles in a periodic lattice. We select monocrystalline Si with negligible material losses and develop a unique method to fabricate nanoparticle arrays on a quartz substrate. By extinction dispersion measurements and electromagnetic analysis, we can identify three types of collective Mie resonances with Q-factors ∼ 500 in the same nanocylinder arrays, including surface lattice resonances, bound states in the continuum, and quasi-guided modes. Our work paves the way for fundamental research in strong light-matter interactions and the design of highly efficient light-emitting metasurfaces.

Aiming at the removal of radioactive cobalt ions from water by graphene oxide (GO), the adsorption mechanism of Co2+ on graphene oxide was analyzed using the quantum chemical calculation software Gaussian 16 based on density functional theory. The influence of material structure factors such as carboxyl groups, hydroxyl groups, epoxy groups and graphene sheets as well as external environmental factors such as pH, temperature and interfering ions on the adsorption effect was determined, and the influence of external environment was verified through experiments. Through calculation and experiment, it was found that the existence of oxygen-containing functional groups on graphene oxide can improve the adsorption efficiency of the material appropriately, and increasing the pH under acidic conditions was also helpful to improve the adsorption effect. The material had certain selectivity for Co2+, and the adsorption capacity and selectivity could be further improved when it was modified by increasing hydroxyl groups.

The efficient segregation of radioactive nuclides from low-level radioactive liquid waste (LLRW) is paramount for nuclear emergency protocols and waste minimization. Here, we synthesized Na3FePO4CO3 (NFPC) via a one-pot hydrothermal method and applied it for the first time to the selective separation of Sr2+ from simulated LLRW. Static adsorption experimental results indicated that the distribution coefficient Kd remained above 5000 mL·g−1, even when the concentration of interfering ions was more than 40 times that of Sr2+. Furthermore, the removal efficiency of Sr2+ showed no significant change within the pH range of 4 to 9. The adsorption of Sr2+ fitted the pseudo-second-order kinetic model and the Langmuir isotherm model, with an equilibrium time of 36 min and a maximum adsorption capacity of 99.6 mg·g−1. Notably, the adsorption capacity was observed to increment marginally with an elevation in temperature. Characterization analyses and density functional theory (DFT) calculations elucidated the adsorption mechanism, demonstrating that Sr2+ initially engaged in an ion exchange reaction with Na+. Subsequently, Sr2+ coordinated with four oxygen atoms on the NFPC (100) facet, establishing a robust Sr-O bond via orbital hybridization.

Abstract Histone deacetylase 6 (HDAC6) is one of the key histone deacetylases (HDACs) that regulates various cellular functions including clearance of misfolded protein and immunological responses. Considerable evidence suggests that HDAC6 is closely related to amyloid and tau pathology, the two primary hallmarks of Alzheimer's disease (AD). It is still unclear whether HDAC6 expression changes with amyloid deposition in AD during disease progression or HDAC6 may be regulating amyloid phagocytosis or neuroinflammation or other neuropathological changes in AD. In this work, the pathological accumulation of HDAC6 in AD brains over age as well as the relationship of its regulatory activity ‐ with amyloid pathogenesis and pathophysiological alterations is aimed to be enlightened using the newly developed HDAC6 inhibitor (HDAC6i) PB118 in microglia BV2 cell and 3D‐AD human neural culture model. Results suggest that the structure‐based rational design led to biologically compelling HDAC6i PB118 with multiple mechanisms that clear Aβ deposits by upregulating phagocytosis, improve tubulin/microtubule network by enhancing acetyl α‐tubulin levels, regulate different cytokines and chemokines responsible for inflammation, and significantly reduce phospho‐tau (p‐tau) levels associated with AD. These findings indicate that HDAC6 plays key roles in the pathophysiology of AD and potentially serves as a suitable pharmacological target through chemical biology‐based drug discovery in AD.

Diesel exhaust (DE) is an important pollution source widely existing in the living and production environment, which is closely related to the health of the public and occupational groups. The International Agency for Research on Cancer has classified DE as a Group 1 carcinogen. Considering the negative health impacts on the respiratory system due to DE exposure in vitro, it is crucial to apply reliable test systems allowing accurate assessment of the biological effects of DE. The exposure technology of respiratory system in vitro is considered as one of the feasible measures to implement the 3R (reduce, refine, and replace) principle in animal experiments. Compared with the traditional submerged culture in vitro models, the air-liquid interface (ALI) exposure technology has the advantages including fewer influencing factors, easier exposure condition control, and shorter exposure cycle. ALI has become an important tool to study molecular events associated with physiology and pathology of respiratory system, and action modes and interactions of different cell types. Also, ALI has been increasingly widely used because it can simulate the actual processes of human respiratory system cells and/or tissues to DE exposure. This review was intended to introduce the development and advantages of ALI exposure technology, and further summarized the application progress of ALI exposure technology in studying the respiratory toxicity induced by DE exposure in vitro, so as to provide new ideas and pathways for the use of ALI exposure technology in the study of biomarkers and mechanisms of respiratory toxicity associated with DE exposure, and provide basic data to screen and promote biomarkers for exposed populations.

Pseudorabies virus (PRV) belongs to the Alphaherpesvirinae subfamily and serves as an exceptional animal model for investigating the infection mechanism of Herpes simplex virus type 1. Notably, PRV has the capability to infect a wide range of mammals, including humans, highlighting its potential as an overlooked zoonotic pathogen. The attachment and entry steps of PRV into host cells are crucial to accomplish its life cycle, which involve numerous cellular factors. In this mini review, we offer a comprehensive summary of current researches pertaining to the role of cellular factors in PRV attachment and entry stages, with the overarching goal of advancing the development of novel antiviral agents against this pathogen.

Highlights 1. Incorporating IMRT and adjuvant chemotherapy into the treatment of locally advanced cervical cancer is highly effective. 2. IMRT is associated with a reduced loco-regional relapse. 3. Adding adjuvant TP chemotherapy could diminish tumor hematological spread. 4. Toxicity profiles were mild and manageable.

Herein, a series of novel O-alkyl ferulamide derivatives were designed and synthesised through the multi-target-directed ligands (MTDLs) strategy. The biological activities in vitro showed that compounds 5a, 5d, 5e, 5f, and 5h indicated significantly selective MAO-B inhibitory potency (IC50 = 0.32, 0.56, 0.54, 0.73, and 0.86 μM, respectively) and moderate antioxidant activity. Moreover, compounds 5a, 5d, 5e, 5f, and 5h showed potent anti-inflammatory properties, remarkable effects on self-induced Aβ1-42 aggregation, and potent neuroprotective effect on Aβ1-42-induced PC12 cell injury. Furthermore, compounds 5a, 5d, 5e, 5f, and 5h presented good blood–brain barrier permeation in vitro and drug-like properties. More interesting, the PET/CT images with [11C]5f demonstrated that [11C]5f could penetrate the BBB with a high brain uptake and exhibited good brain clearance kinetic property. Therefore, compound 5f would be a promising multi-functional agent for the treatment of AD.

Although the epigenetic regulatory protein histone deacetylase 6 (HDAC6) has been recently implicated in the etiology of Alzheimer's disease (AD), little is known about the role of HDAC6 in the etiopathogenesis of AD and whether HDAC6 can be a potential therapeutic target for AD. Here, we performed positron emission tomography (PET) imaging in combination with histopathological analysis to better understand the underlying pathomechanisms of HDAC6 in AD. We first developed [18F]PB118 which was demonstrated as a valid HDAC6 radioligand with excellent brain penetration and high specificity to HDAC6. PET studies of [18F]PB118 in 5xFAD mice showed significantly increased radioactivity in the brain compared to WT animals, with more pronounced changes identified in the cortex and hippocampus. The translatability of this radiotracer for AD in a potential human use was supported by additional studies, including similar uptake profiles in non-human primates, an increase of HDAC6 in AD-related human postmortem hippocampal tissues by Western blotting protein analysis, and our ex vivo histopathological analysis of HDAC6 in postmortem brain tissues of our animals. Collectively, our findings show that HDAC6 may lead to AD by mechanisms that tend to affect brain regions particularly susceptible to AD through an association with amyloid pathology.

Plasmonic hydrogen sensors have limited sensitivity due to broad spectral features. Here, the authors use a particle swarm optimization algorithm to inversely design a plasmonic metasurface based on a periodic array of Pd nanoparticles, and demonstrate hydrogen detection limit of 250 ppb.

Due to the complex interaction of urban and mountainous floods, assessing flood susceptibility in mountainous urban areas presents a challenging task in environmental research and risk analysis. Data-driven machine learning methods can evaluate flood susceptibility in mountainous urban areas lacking essential hydrological data, utilizing remote sensing data and limited historical inundation records. In this study, two ensemble learning algorithms, Random Forest (RF) and XGBoost, were adopted to assess the flood susceptibility of Kunming, a typical mountainous urban area prone to severe flood disasters. A flood inventory was created using flood observations from 2018 to 2022. The spatial database included 10 explanatory factors, encompassing climatic, geomorphic, and anthropogenic factors. Artificial Neural Network (ANN) and Support Vector Machine (SVM) were selected for model comparison. To minimize the influence of expert opinions on model training, this study employed a strategy of uniformly random sampling in historically non-flooded areas for negative sample selection. The results demonstrated that (1) ensemble learning algorithms offer higher accuracy than other machine learning methods, with RF achieving the highest accuracy, evidenced by an area under the curve (AUC) of 0.87, followed by XGBoost at 0.84, surpassing both ANN (0.83) and SVM (0.82); (2) the interpretability of ensemble learning highlighted the differences in the potential distribution of the training data’s positive and negative samples. Feature importance in ensemble learning can be utilized to minimize human bias in the collection of flooded-site samples, more targeted flood susceptibility maps of the study area’s road network were obtained; and (3) ensemble learning algorithms exhibited greater stability and robustness in datasets with varied negative samples, as evidenced by their performance in F1-Score, Kappa, and AUC metrics. This paper further substantiates the superiority of ensemble learning in flood susceptibility assessment tasks from the perspectives of accuracy, interpretability, and robustness, enhances the understanding of the impact of negative samples on such assessments, and optimizes the specific process for urban flood susceptibility assessment using data-driven methods.

Abstract Background To investigate the expression of elastin in the conjoint facial sheath (CFS) in patients with severe unilateral congenital blepharoptosis in different age groups. Methods Twenty-seven cases of severe unilateral congenital blepharoptosis (27 eyes) were treated with CFS + LM complex suspension from January 2020 to July 2020. Within that sample, 9 patients were over 18 years old, 9 patients were 13 to 17 years old and 9 patients were 5 to 12 years old. CFS and LM specimens were collected during CFS + LM complex suspension surgery. In the CFS specimens, the elastic fibers were observed by Victoria Blue staining. The elastin expression levels of the three groups of specimens were determined and analyzed by immunofluorescent staining and Western blotting. Results Victoria Blue staining showed that elastic fibers were abundant in CFS tissue. Moreover, immunofluorescent staining showed strong positive expression of elastin in the CFS and LM. Furthermore, in the child group, the Western blot results demonstrated that the expression of elastin was higher in the CFS than in the LM (P

Background: Primary liver cancer, around 75%–85% are hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China in June 2017, which were updated by the National Health Commission in December 2019, additional high-quality evidence has emerged from researchers worldwide regarding the diagnosis, staging, and treatment of liver cancer, that requires the guidelines to be updated again. The new edition (2022 Edition) was written by more than 100 experts in the field of liver cancer in China, which not only reflects the real-world situation in China, but also may re-shape the nationwide diagnosis and treatment of liver cancer. Key Messages: The new guideline aims to encourage the implementation of evidence-based practice, and improve the national average five-year survival rate for patients with liver cancer, as proposed in the "Health China 2030 Blueprint."

Abstract Background This study aimed to analyze the clinical and pathological features of extrauterine endometrial stromal sarcoma (EESS) and explore an effective therapeutic regimen to reduce the recurrence rate in low-grade EESS patients. Methods Ten LG-EESS patients who were treated at the Chinese Academy of Medical Sciences Cancer Institute and Hospital from June 1999 to June 2019 were collected and analyzed. Results (1) Patient demographics are summarized in manuscript. Preoperative CA125 examination showed that 8 patients had a median level of 49.5 U/L (15.4–168.0 U/L). (2) All ten patients underwent tumor cytoreductive surgery. Five patients underwent optimal tumor resection and achieved an R0 resection. After the initial surgery, 7 patients who had multiple metastasis were treated with adjuvant chemotherapy, 2 patients with vaginal ESS were treated with chemotherapy and radiation therapy, and 6 patients with ER/PR positive received hormone therapy with or without chemotherapy. (2) Most EESS patients had multiple tumors. The omentum was the most commonly affected site, followed by the ovaries. (3) The median follow-up was 94 (range: 27–228) months, and recurrence was observed in 3 patients (n = 10, 30%) who underwent non-optimal surgery and no hormone therapy. The 5-year and 10-year DFS rates were both 70%, as shown in Fig. 2. OS was both 100% at 5 and 10 years. Conclusion As a conclusion, EESS is a rare disease and LG-EESS has a good prognosis. Surgery remains the available treatment for patients. LG-EESS has a risk of late recurrence which requires a long-term follow-up. With a limited sample size, our study shows optimal tumor reductive surgery and adjuvant hormone therapy may significantly reduce the risk of recurrence.

Abstract Background Current findings on the impact of weather conditions on osteoarthritis (OA) and rheumatoid arthritis (RA) are sparse and not conclusive. This study aimed to investigate the relationship between temperature change and OA/RA admission. Methods Daily OA/RA admission, meteorological data and pollutants from 1 January 2014 to 31 December 2017 in Hefei, China, were collected. We quantified the relationship between ambient temperature and OA/RA admission using a distributed lag nonlinear model (DLNM). Stratified analyses by gender and age were also examined. Results Temperature decrease was significantly associated with RA admission (25th percentile of temperature versus 50th percentile of temperature), with the acute and largest effect at current days lag (RR: 1.057, 95%CI: 1.005–1.111). However, no significant association between temperature and OA admission was observed. When conducting subgroup analyses by individual characteristics, we found that females and patients aged 41–65 years were more vulnerable to temperature decrease than males, patients aged 0–40 and ≧66 years, respectively. Conclusions This study suggested that temperature decrease was a risk factor for increases in RA admission. Females and patients aged 41–65 years were particularly vulnerable to the effect of temperature decrease.

AIM:To investigate the main clinical features, pathogen distribution and drug sensitivity of lacrimal angiitis, and to provide evidence for clinical diagnosis and treatment.METHODS:Retrospective study. A total of 45 patients(45 eyes)diagnosed with lacrimal angiitis in Hebei Eye Hospital from December 2016 to October 2020 were selected to analyze the general information, clinical manifestations and previous treatment history, bacterial culture results, and drug sensitivity test results.RESULTS:All 45 patients had monocular disease, including 21 eyes with tears, increased secretion, conjunctival congestion in inner canthus, 14 eyes with red and swollen inner canthus, 6 eyes similar to eyelid cyst, and 4 eyes were found and diagnosed during routine preoperative examination. 27 eyes were previously diagnosed with other eye diseases, and the misdiagnosis rate was 60.0%. The positive rate of bacterial culture was 80.0%(36/45), Staphylococcus epidermidis was the most common, followed by Streptococcus; 52.8%(19/36)of the patients were infected with multidrug-resistant bacteria. The sensitivity rate of bacteria to fluoroquinolones(82.9%, 97/117)was higher than that of aminoglycosides(70.1%, 68/97)and cephalosporins(68.1%, 111/163). Except vancomycin, rifampicin, levofloxacin and chloramphenicol were highly sensitive to Gram-positive bacteria.CONCLUSION: Staphylococcus epidermidis is the most common pathogen of dacryocystitis, followed by Streptococcus. Levofloxacin and rifampicin can be the first choice antibiotics for local anti-infection. Rational drug use can reduce the formation of multidrug-resistant bacteria. The cure rate can be improved by complete removal of stones by incision and plasty of lacrimal canaliculus.

ObjectiveTo evaluate the surgical outcomes of modified combined fascia sheath (CFS) and levator muscle (LM) complex suspension for the correction of severe congenital blepharoptosis in pediatric patients.MethodsPediatric patients with severe congenital blepharoptosis were enrolled form July 2017 to July 2021. All patients were divided into two groups according to their age (group A ≤ 7 years; group B > 7 years) and received CFS + LM suspension surgery. Main surgical outcome indexes include margin reflex distance 1 (MRD1) and MRD1 regression. Postoperative complications such as lagophthalmos (LAG), conjunctival prolapse, exposure keratopathy and trichiasis were documented.ResultsFifty patients (60 eyes) were enrolled, including 17 patients (18 eyes) in group A and 33 patients (42 eyes) in group B. The MRD1 in group A was 3.06 ± 0.64 mm at 6 months after the operation, and the MRD1 in group B was 2.64 ± 0.69 mm 6 months postoperatively which is significantly lower than that of group A (P = 0. 044). At the last visit, however, the MRD1 in group A was 3.00 ± 0.69 mm and the MRD1 in group B was 2.64 ± 0.70 mm. There was no significant difference in MRD1 between two groups in long term (P = 0.255). Additionally, there were a variety of degrees of MRD1 regression, especially in the first month after the operation in both groups (both P

Abstract Background As a nutritional index, preoperative serum prealbumin highly correlates with surgical complications. However, the correlation between preoperative prealbumin and postoperative complications remains unclear in liver transplantation (LT). Methods A total of 191 patients who underwent LT between 2015 and 2019 were included in the retrospective analysis. According to a cut-off value calculated from a receiver operating characteristic (ROC) curve, the patients were divided into normal and low preoperative prealbumin groups. Univariable and multivariable logistic regression analyses were used to identify independent risk factors for postoperative complications. In addition, patients were divided into subgroups by Model for End-stage Liver Disease (MELD) score, and the association between preoperative prealbumin and postoperative complications was also assessed in each group. Results A total of 111 (58.1%) patients were included in the low prealbumin group based on a cut-off value of 120 mg/L. The area under the ROC curve (AUC) was 0.754 (95% confidence interval [CI] 0.678–0.832). Low prealbumin (95% CI 1.51–12.8, P = 0.007) was identified as a predictor for postoperative complications based on multivariable regression. In the low and normal prealbumin groups, the prevalence rates of postoperative complications were 27.5% and 8.0% (P = 0.003) in the MELD score ≤ 15 subgroup and 53.3% and 20.0% (P = 0.197) in the MELD score > 15 subgroup, respectively. Conclusions Preoperative prealbumin was associated with postoperative complications in LT, and preoperative nutritional support benefitted postoperative recovery, especially for patients with low MELD scores.

AIM: To explore the pathogenic bacteria and drug resistance of acute dacryocystitis, and to provide a guide for rational clinical medication.METHODS: Lacrimal sac pus samples from 80 acute dacryocystitis cases were collected for bacterial culture and drug sensitivity test in Hebei Provincial Eye Hospital from January 2014 to October 2019. The change of detection rate of pathogenic bacteria in different years, the species of pathogenic bacteria of acute dacryocystitis, the main pathogenic bacteria, drug sensitivity and drug resistance of acute dacryocystitis, and the average detection rate of pathogenic bacteria in acute dacryocystitis were analyze.RESULTS:Totally 56 samples were positive for pathogenic bacteria, including 55 cases of bacteria and 1 case of fungi. The average detection rate was 70%. The detection rate of pathogenic bacteria strains was gradually decreasing year by year, and there were various types of pathogenic bacteria strains detected from samples. In addition, Gram-positive cocci was the main pathogenic bacteria of acute dacryocystitis, accounting for 68%(38 cases), of which, staphylococcus aureus accounted for 38%(21 cases). What's more, most Gram-positive cocci were sensitive to rifampin, levofloxacin, and chloramphenicol, and Gram-negative bacilli were more sensitive to tobramycin, levofloxacin, ciprofloxacin, and gentamicin. Fifty-five cases of bacterial samples were obviously resistant to the first and second generation cephalosporins.CONCLUSION: Gram-positive cocci constitute the main pathogenic bacteria of acute dacryocystitis, and levofloxacin can be used as the first choice of topical antibiotics for the treatment of acute dacryocystitis.

BackgroundAlmost 40% of patients with kidney renal clear cell carcinoma (KIRC) with advanced cancers eventually develop to metastases, and their 5-year survival rates are approximately 10%. Aberrant DNA methylations are significantly associated with the development of KIRC. The aim of our present study was to identify suitable ferroptosis- and immune-related (FI) biomarkers correlated with aberrant methylations to improve the prognosis and diagnosis of KIRC.MethodsChAMP and DESeq2 in R (3.6.2) were used to screen the differentially expressed methylation probes and differentially expressed genes, respectively. Univariate and multivariate Cox regression were used to identify the overall survival (OS)–related biomarkers.ResultsWe finally identified five FI biomarkers (CCR4, CMTM3, IFITM1, MX2, and NR3C2) that were independently correlated with the OS of KIRC. The area under the curve value of the receiver operating characteristic value of prognosis model was 0.74, 0.68, and 0.72 in the training, validation, and entire cohorts, respectively. The sensitivity and specificity of the diagnosis model were 0.8698 and 0.9722, respectively. In addition, the prognosis model was also significantly correlated with several immune cells and factors.ConclusionOur present study suggested that these five FI-DEGs (CCR4, CMTM3, IFITM1, MX2, and NR3C2) could be used as prognosis and diagnosis biomarkers for patients with KIRC, but further cross-validation clinical studies are still needed to confirm them.

Background: Primary liver cancer, around 90% are hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer (2017 Edition) in 2018, additional high-quality evidence has emerged with relevance to the diagnosis, staging, and treatment of liver cancer in and outside China that requires the guidelines to be updated. The new edition (2019 Edition) was written by more than 70 experts in the field of liver cancer in China. They reflect the real-world situation in China regarding diagnosing and treating liver cancer in recent years. Key Messages: Most importantly, the new guidelines were endorsed and promulgated by the Bureau of Medical Administration of the National Health Commission of the People’s Republic of China in December 2019.

Abstract Background Esophageal cancer is one of the most common cancers worldwide with poor prognosis and high mortality. The transcription factor SNAI1, encoding Snail1, is important for metastatic progression in esophageal cancer whereas the microRNA (miRNA)-203 has been shown to function as an inhibitor of metastasis in EC. The Snail1 protein is stabilized in EC partially by the deubiquitinating enzyme USP26; however, how USP26 is regulated is not completely known. Methods Expression of SNAI1 and USP26 messenger RNA (mRNA) and miR-203 was performed in datasets within The Cancer Genome Atlas and Gene Expression Omnibus, respectively. Expression of Snail1 and USP26 protein and miR-203 was determined in the normal esophageal cell line HET-1A and EC cell lines Kyse150 and TE-1 using western blot and quantitative polymerase chain reaction, respectively. TargetScan was used for in situ prediction of miR-203 targets and in vitro heterologous reporter assays using the wild-type and miR-203 seed mutant of the 3′ Untranslated region (UTR) of USP26 were used to investigate whether USP26 is a target of miR-203. Effects of increasing miR-203 using MIR203A/5P mimic on USP26 and Snail1 in the HET-1A, Kyse150 and TE-1 cell lines were performed using western blot and cycloheximide-based protein stability analysis. Effects of modulating miR-203 in Kyse150 and TE-1 cell lines on in vitro pro-metastatic effects were analyzed by invasion assay, scratch wound-healing assay, and chemosensitivity to 5-fluoruracil (5-FU). In vivo lung metastasis assay was used to study the effect of modulating miR-203 in Kyse150 cells. Results SNAI1 mRNA and HSA/MIR203 was higher and lower, respectively, in EC patients compared to tumor-adjacent normal tissues. No changes in expression of USP26 mRNA were observed in these datasets. MIR/203 expression was downregulated whereas protein expression of both Snail1 and USP26 were higher in EC cell lines Kyse150 and TE-1 compared to normal esophageal cell line HET-1A. USP26 was predicted as a potential target of miR-203 by TargetScan Release 2.0. Reporter assays confirmed USP26 as a target of miR-203 in the EC cell lines. Transfection of EC cell lines with MIR203 mimic decreased USP26 protein expression and Snail1 protein stability indicating the ability of miR-203 to regulate Snail1 protein levels via USP26. Exogenous increase in miR-203 in the EC cell lines significantly inhibited Snail-1 mediated in vitro pro-metastatic function of invasion, wound-healing, and increased chemosensitivity to 5-FU. Finally, overexpression of miR-203 inhibited in vivo lung metastasis of Kyse150 cells, which was reversed following overexpression of USP26, indicating a direct role of miR-203-mediated regulation of USP26 in metastatic progression of EC. Conclusions Cumulatively, these results establish an important mechanism by which decrease in miR-203 expression potentiates metastatic progression in EC via USP26-mediated stabilization of Snail1. Hence, miR-203 can serve as a biomarker of metastasis in EC and is a potential target for therapeutic intervention in EC.

Abstract Purpose Hepatocellular carcinoma (HCC) is a common malignant cancer and the third leading cause of death worldwide. The molecular mechanism of HCC remains unclear. Recent studies have demonstrated that the ubiquitin‐proteasome system (UPS) is associated with HCC. Ubqln2, a member of the UPS, is abnormally expressed in HCC. However, whether Ubqln2 is associated with HCC prognosis remains unknown. Patients and Methods We analyzed the associations between overall survival and various risk factors in 355 HCC tissue samples obtained from the Cancer Genomic Atlas (TCGA) database at the mRNA level and in 166 HCC tissue samples from Southwest Hospital at the protein level. qRCR was used to determinate Ubqln2 expression in cancer and noncancerous tissues. The association between Ubqln2 and Ki‐67 was analyzed by immunohistochemistry. The association between Ubqln2 expression and survival was analyzed using Kaplan‐Meier curve and Cox proportional hazards models. A nomogram was used to predict the impact of Ubqln2 on prognosis. Mutated genes were analyzed to determine the potential mechanism. Results Ubqln2 highly expressed in HCC tissues. The Ubqln2 mRNA level had significant relations with UICC tumor stage (P = .022), UICC stage (P = .034) and resection potential (P = .017). Concordantly, the Ubqln2 protein was closely associated with tumor size (P = .005), UICC stage (P = .012), and recurrence (P = .009). Ubqln2 was highly expressed in HCC and positively associated with poor survival. The nomogram precisely predicted the prognosis of HCC patients with high or low Ubqln2 expression. A genomic waterfall plot suggested that Ubqln2 expression was closely associated with mutated CTNNB1. Conclusion Our findings reveal that Ubqln2, an independent risk factor for HCC, is a potential prognostic marker in HCC patients. Ubqln2 expression is positively associated with mutated CTNNB1.

AIM: To explore the clinical efficacy and prognosis of glucocorticoid combined with surgical method for TAO-related upper eyelid retraction. METHODS: A total of 96 patients(146 eyes)with upper eyelid retraction who were admitted to the plastic surgery clinic and ward of our hospital from February 2014 to July 2018 were selected. According to different treatment methods, the patients were divided into GI group: 72 patients with TAO-related upper eyelid retraction treated with glucocorticoids; 72 patients with GS group: 48 patients with TAO-related upper eyelid retraction treated with glucocorticoid combined with conjunctival approach. After treatment, the upper eyelid muscle strength, the treatment effect, the height of the eyelid fissure, and the actual double eyelid width were compared between the two groups of patients.RESULTS: After treatment, the patients in GI group had significant treatment effects in 32 people and 47 eyes, and the patients in the GS group had significant treatment effects in 16 and 25 eyes. The patients in the GS group had significant treatment effects in 46 cases and 71 eyes, and there were no significant treatment effects in 2 people and 3 eyes. Compared with the GS group, the treatment effect of the GS group was significantly higher than that of the GI group(PP>0.05). According to the table, before treatment, the height of the eyelid fissures in the GI group and the GS group were 11.25±1.85 and 11.31±1.46mm, and the data in the two groups were similar(P>0.05). The height of the eyelid fissures was 10.14±1.23mm, 3mo after treatment was 8.52±1.01mm. Compared with the GI group, the recovery of blepharoplasty was better in the GS group than in the GI group(PP>0.05). Three months after treatment, the upper eyelid muscle strength was 15.64±1.34, 14.36±1.56mm. There was no significant difference in upper eyelid muscle between the GI group and the GS group(P>0.05). The results showed that before treatment, the patients with GI group and GS group actually had a double eyelid width of 5.12±1.64 and 5.16±1.48mm. The data in the two groups were similar(P>0.05). Three months after treatment, the double eyelid was actually The widths were 7.67±2.95 and 8.49±2.39mm, respectively. Compared with the GI group, the GI group had a better change in the double eyelid width than the GI group(PCONCLUSION: Glucocorticoid combined with conjunctival approach Müller myectomy is better for patients with upper eyelid retraction, which can significantly improve the height of the eyelid fissure and the width of the double eyelid.

Cloud and cloud shadow detection is an important preprocess before using satellite images for different applications. It can be considered as a classification process, in which the objective pixels are partitioned into cloud/cloud shadow or non-cloud/non-cloud shadow classes. However, some cloud pixels, especially the thin cloud pixels, can be considered as a mixture of reflectances of clouds and land objects. In fuzzy clustering, the data points can belong to two or more clusters; hence, fuzzy clustering may better characterize the status of one given pixel belonging to clouds or non-clouds. The fuzzy c-means method (FCM), one typical fuzzy clustering method, was utilized in this study for cloud and cloud shadow detection. In addition, the “flood-fill” morphological transformation may misclassify some clear-sky areas surrounded by clouds as cloud shadows as a whole, so a modified cloud shadow index calculation was proposed. Moreover, a cloud and cloud shadow spatial matching strategy based on the projection direction and spatial coexistence was used to exclude some pseudo cloud shadows. Fewer predefined parameters and spectral bands are needed is one characteristic of the proposed method. In this study, 41 scenes including 27 Landsat ETM+ images in eight latitude zones and 14 Landsat OLI images comprising seven land cover types, including barren, forest, grass, shrubland, urban, water, and wetlands areas, with percentages of cloud cover from 4.99% to 97.63%, were utilized to confirm the validity of the FCM. The detected results demonstrate that the thick and thin clouds along with their associated cloud shadows can be precisely extracted by using the FCM. Compared with the function of mask (Fmask) method, the FCM has relatively lower producer agreement rates, but it misclassifies as clouds fewer clear-sky pixels; compared with the support vector machine (SVM) method, the FCM can achieve better cloud detection accuracy. The results demonstrate that the FCM can attain a better balance between cloud pixel detection and non-cloud pixel exclusion.

BackgroundImplant-based breast reconstruction is increasingly becoming the most common method of postmastectomy breast reconstruction in use today. As the traditional autologous reconstruction technique, latissimus dorsi flap (LDF) is employed by surgeons for reconstruction after breast cancer surgery, including partial mastectomy, modified radical mastectomy, and others. The authors aim to compare patient-reported outcomes (PROs) and complications between the SIS matrix-assisted direct-to-implant (DTI) breast reconstruction and the autologous LDF breast reconstruction.MethodsPatients undergoing the SIS matrix-assisted DTI reconstruction or mastectomy with LDF reconstruction or partial mastectomy with mini latissimus dorsi flap (MLDF) reconstruction were enrolled in a single institution from August 2010 to April 2019. Patients were included for analysis and divided into three groups: those who underwent LDF reconstruction, those who underwent MLDF reconstruction, and patients who underwent SIS matrix-assisted DTI breast reconstruction. PROs (using the BREAST-Q version 2.0 questionnaire) and complications were evaluated.ResultsA total of 135 patients met the inclusion criteria: 79 patients (58.5%) underwent SIS matrix-assisted DTI, 29 patients (21.5%) underwent LDF breast reconstruction, and 27 patients (20%) underwent MLDF breast reconstruction. PROs and complication rates between LDF reconstruction group and MLDF reconstruction group showed no statistically significant differences. Furthermore, BREAST-Q responses found that patients in the whole autologous LDF reconstruction group had better psychosocial well-being, showing a mean score of 84.31 ± 17.28 compared with SIS matrix-assisted DTI reconstruction, with a mean score of 73.52 ± 19.96 (p = 0.005), and expressed higher sexual well-being (69.65 ± 24.64 vs. 50.95 ± 26.47; p = 0.016). But there were no statistically significant differences between the two groups for postoperative complications.ConclusionThis retrospective study showed no statistically significant differences between LDF breast reconstruction and MLDF breast reconstruction. However, patients in the whole autologous LDF reconstruction group yielded superior PROs than patients in the SIS matrix-assisted DTI reconstruction group in the psychosocial well-being and sexual well-being domains.

A chipless sensor in the protocol of ultra wideband radio frequency identification (UWB-RFID) is proposed in the paper. This sensor, used to detect methane at room temperature, is configured by a planar patch antenna plus a U slot on which interdigitated fingers electrodes (IDE) with load of palladium decorated single walled carbon nanotubes (Pd-SWCNTs) are embedded. The sensor can cover the entire UWB spectrum except for the band that produce band-gap. The amplitudes and frequencies of the band-gap are designated as the signatures modulated and reflecting the status quo of methane retrieved by Pd-SWCNTs. The sensor is validated by an approximate combination of the analytical and numerical method. Results show that if the concentration of methane is increased from 0 ppm to 100 ppm at room temperature, the identifiable sensitivity can be achieved by -9.32 dB in terms of the scheme of the amplitude modulation of band-gap frequency; or, the identifiable sensitivity can be achieved by -11.30 dB in terms of the scheme of the frequency modulation of band-gap frequency. [ABSTRACT FROM AUTHOR]

The sigma-1 receptor (σ1R) is a unique intracellular protein. σ1R plays a major role in various pathological conditions in the central nervous system (CNS), implicated in several neuropsychiatric disorders. Imaging of σ1R in the brain using positron emission tomography (PET) could serve as a noninvasively tool for enhancing the understanding of the disease's pathophysiology. Moreover, σ1R PET tracers can be used for target validation and quantification in diagnosis. Herein, we describe the radiosynthesis, in vivo PET/CT imaging of novel σ1R 11C-labeled radioligands based on 6-hydroxypyridazinone, [11C]HCC0923 and [11C]HCC0929. Two radioligands have high affinities to σ1R, with good selectivity. In mice PET/CT imaging, both radioligands showed appropriate kinetics and distributions. Additionally, the specific interactions of two radioligands were reduced by compounds 13 and 15 (self-blocking). Of the two, [11C]HCC0929 was further investigated in positive ligands blocking studies, using classic σ1R agonist SA 4503 and σ1R antagonist PD 144418. Both σ1R ligands could extensively decreased the uptake of [11C]HCC0929 in mice brain. Besides, the biodistribution of major brain regions and organs of mice were determined in vivo. These studies demonstrated that two radioligands, especially [11C]HCC0929, possessed ideal imaging properties and might be valuable tools for non-invasive quantification of σ1R in brain. KEY WORDS: σ1R, PET, Brain imaging, 6-Hydroxypyridazinone, 11C-labeled radioligand

Abstract Background Pancreatic cancer is a highly lethal malignancy with poor prognosis. Anillin (ANLN), an actin binding protein, is upregulated and plays an important role in many malignant tumors. However, the precise role of ANLN in pancreatic cancer remains unclear. Methods The expression of ANLN and its association with pancreatic cancer patient survival were analyzed using an online database and confirmed by immunohistochemistry. The ANLN protein expression in pancreatic cancer cell lines was detected by Western blot. Cell proliferation, colony formation and transwell assays in vitro and in vivo tumor growth were used to determine the role of ANLN in pancreatic cancer. Gene expression microarray analysis and a series of in vitro assays were used to elucidate the mechanisms of ANLN regulating pancreatic cancer progression. Results We found that the ANLN expression was significantly upregulated in pancreatic cancer tissues and cell lines. The high expression of ANLN was associated with tumor size, tumor differentiation, TNM stage, lymph node metastasis, distant metastasis and poor prognosis in pancreatic cancer. ANLN downregulation significantly inhibited cell proliferation, colony formation, migration, invasion and tumorigenicity in nude mice. Meanwhile, we found that ANLN knockdown inhibited several cell-cell adhesion related genes, including the gene encoding LIM and SH3 protein 1 (LASP1). LASP1 upregulation partially reversed the tumor-suppressive effect of ANLN downregulation on pancreatic cancer cell progression. Moreover, we found that ANLN downregulation induced the expression of miR-218-5p which inhibited LASP1 expression through binding to its 3’UTR. We also found that ANLN-induced enhancer of zeste homolog 2 (EZH2) upregulation was involved in regulating miR-218-5p/LASP1 signaling axis. EZH2 upregulation or miR-218-5p downregulation partially reversed the tumor-suppressive effect of ANLN downregulation on pancreatic cancer cell progression. Conclusion ANLN contributed to pancreatic cancer progression by regulating EZH2/miR-218-5p/LASP1 signaling axis. These findings suggest that ANLN may be a candidate therapeutic target in pancreatic cancer.