Search

Efforts to develop peripheral blood-derived nature killer (NK) cells into therapeutic products have been hampered by these cells' low abundance and histoincompatibility. On the other hand, derivation of NK-like cells from more abundant cell sources such as

The pathophysiology of LaPeyronie's disease (PD) is considered to be multifactorial, involving genetic predisposition, trauma, inflammation and altered wound healing. However, these factors have not yet been validated using animal models. In this study, we

This paper evaluates the current status of global modeling of the organic aerosol (OA) in the troposphere and analyzes the differences between models as well as between models and observations. Thirty-one global chemistry transport models (CTMs) and general circulation models (GCMs) have participated in this intercomparison, in the framework of AeroCom phase II. The simulation of OA varies greatly between models in terms of the magnitude of primary emissions, secondary OA (SOA) formation, the number of OA species used (2 to 62), the complexity of OA parameterizations (gas-particle partitioning, chemical aging, multiphase chemistry, aerosol microphysics), and the OA physical, chemical and optical properties. The diversity of the global OA simulation results has increased since earlier AeroCom experiments, mainly due to the increasing complexity of the SOA parameterization in models, and the implementation of new, highly uncertain, OA sources. Diversity of over one order of magnitude exists in the modeled vertical distribution of OA concentrations that deserves a dedicated future study. Furthermore, although the OA / OC ratio depends on OA sources and atmospheric processing, and is important for model evaluation against OA and OC observations, it is resolved only by a few global models. The median global primary OA (POA) source strength is 56 Tg a-1 (range 34-144 Tg a-1) and the median SOA source strength (natural and anthropogenic) is 19 Tg a-1 (range 13-121 Tg a-1). Among the models that take into account the semi-volatile SOA nature, the median source is calculated to be 51 Tg a-1 (range 16-121 Tg a-1), much larger than the median value of the models that calculate SOA in a more simplistic way (19 Tg a-1; range 13-20 Tg a-1, with one model at 37 Tg a-1). The median atmospheric burden of OA is 1.4 Tg (24 models in the range of 0.6-2.0 Tg and 4 between 2.0 and 3.8 Tg), with a median OA lifetime of 5.4 days (range 3.8-9.6 days). In models that reported both OA and sulfate burdens, the median value of the OA/sulfate burden ratio is calculated to be 0.77; 13 models calculate a ratio lower than 1, and 9 models higher than 1. For 26 models that reported OA deposition fluxes, the median wet removal is 70 Tg a-1 (range 28-209 Tg a-1), which is on average 85% of the total OA deposition. Fine aerosol organic carbon (OC) and OA observations from continuous monitoring networks and individual field campaigns have been used for model evaluation. At urban locations, the model-observation comparison indicates missing knowledge on anthropogenic OA sources, both strength and seasonality. The combined model-measurements analysis suggests the existence of increased OA levels during summer due to biogenic SOA formation over large areas of the USA that can be of the same order of magnitude as the POA, even at urban locations, and contribute to the measured urban seasonal pattern. Global models are able to simulate the high secondary character of OA observed in the atmosphere as a result of SOA formation and POA aging, although the amount of OA present in the atmosphere remains largely underestimated, with a mean normalized bias (MNB) equal to -0.62 (-0.51) based on the comparison against OC (OA) urban data of all models at the surface, -0.15 (+0.51) when compared with remote measurements, and -0.30 for marine locations with OC data. The mean temporal correlations across all stations are low when compared with OC (OA) measurements: 0.47 (0.52) for urban stations, 0.39 (0.37) for remote stations, and 0.25 for marine stations with OC data. The combination of high (negative) MNB and higher correlation at urban stations when compared with the low MNB and lower correlation at remote sites suggests that knowledge about the processes that govern aerosol processing, transport and removal, on top of their sources, is important at the remote stations. There is no clear change in model skill with increasing model complexity with regard to OC or OA mass concentration. However, the complexity is needed in models in order to distinguish between anthropogenic and natural OA as needed for climate mitigation, and to calculate the impact of OA on climate accurately.

We present a new three-dimensional seismic velocity model of the crustal and upper mantle structure for Mauna Loa and Kilauea volcanoes in Hawaii. Our model is derived from the first-arrival times of the compressional and shear waves from about 53,000 events on and near the Island of Hawaii between 1992 and 2009 recorded by the Hawaiian Volcano Observatory stations. The Vp model generally agrees with previous studies, showing high-velocity anomalies near the calderas and rift zones and low-velocity anomalies in the fault systems. The most significant difference from previous models is in V p/Vs structure. The high-Vp and high-V p/Vs anomalies below Mauna Loa caldera are interpreted as mafic magmatic cumulates. The observed low-Vp and high-V p/Vs bodies in the Kaoiki seismic zone between 5 and 15 km depth are attributed to the underlying volcaniclastic sediments. The high-Vp and moderate- to low-Vp/Vs anomalies beneath Kilauea caldera can be explained by a combination of different mafic compositions, likely to be olivine-rich gabbro and dunite. The systematically low-Vp and low-Vp/Vs bodies in the southeast flank of Kilauea may be caused by the presence of volatiles. Another difference between this study and previous ones is the improved Vp model resolution in deeper layers, owing to the inclusion of events with large epicentral distances. The new velocity model is used to relocate the seismicity of Mauna Loa and Kilauea for improved absolute locations and ultimately to develop a high-precision earthquake catalog using waveform cross-correlation data. ©2014. American Geophysical Union. All Rights Reserved.

The aerodynamics and flowfield of a rectangular semiwing equipped with four four-bladed propellers and a 40%-chord full-span plain trailing-edge flap were investigated by using force balance and particle image velocimetry (PIV). The distributed electric propulsion (DEP) wing was tilted from zero to 90-deg angle of attack. The maximum lift coefficient, lift-curve slope, and stall angle of the DEP wing were found to increase significantly with increasing propeller rotation. The DEP wing also exhibited a gradual stall in contrast to the sudden stall of the baseline wing. The lift coefficient of the DEP wing positioned vertically at 90 deg was also found to be greatly increased with increasing propeller rotation. Regardless of the magnitude of propeller rotation, the general pattern and behavior of the lift curve were consistent. The deployment of the flap led to a further increase in the maximum lift coefficient and lift-curve slope but an earlier stall and an increased drag of the DEP wing as compared to the unflapped wing. The flap deflection also led to a lowered lift coefficient in the poststall angle-of-attack regime as compared to the unflapped DEP wing. Gurney flap was also employed to further increase the lift generation of the DEP wing. The lift augmentation produced by the propeller slipstream was supplemented by the PIV flowfield measurements. [ABSTRACT FROM AUTHOR]

Objective: To construct a prediction model for fetal growth restriction (FGR) during the first trimester of pregnancy and evaluate its screening performance. Methods: This was a prospective cohort study of singleton pregnancies that underwent routine ultrasound screening at 11 to 13 + 6 weeks at the Affiliated Suzhou Hospital of Nanjing Medical University between January 2019 and April 2022. Basic clinical information, ultrasound indicators and serum biomarkers of pregnant women were collected. Fetal weight assessment was based on the fetal growth curve for the Southern Chinese population. FGR was diagnosed according to Delphi consensus criteria. Least absolute shrinkage and selection operator (lasso) regression was used to select variables for inclusion in the model. Discrimination, calibration and clinical effectiveness of the model were evaluated in training and validation cohorts. Results: A total of 1188 pregnant women were included, of whom 108 had FGR. Lasso regression identified seven predictive features, including history of maternal hypertension, maternal smoking or passive smoking, gravidity, uterine artery pulsatility index, ductus venosus pulsatility index and multiples of the median values of placental growth factor and soluble fms‐like tyrosine kinase‐1. The nomogram prediction model constructed from these seven variables accurately predicted FGR, and the area under the receiver‐operating‐characteristics curve in the validation cohort was 0.82 (95% CI, 0.74–0.90). The calibration curve and Hosmer–Lemeshow test demonstrated good calibration, and the clinical decision curve and clinical impact curve supported its practical value in a clinical setting. Conclusion: The multi‐index prediction model for FGR has good predictive value during the first trimester. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Xianglei Fu,1 Yanbin Shi,2 Hui Wang,1 Xiaogang Zhao,3 Qifeng Sun,3 Yi Huang,1 Tongtong Qi,1 Guimei Lin1 1School of Pharmaceutical Science, Shandong University, Jinan 250012,People’s Republic of China; 2School of Mechanical & Automotive Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, People’s Republic of China; 3The Second Hospital of Shandong University, Jinan 250033, People’s Republic of ChinaCorrespondence: Guimei LinSchool of Pharmaceutical Science, Shandong University, 44 West Wenhua Road, Jinan 250012, People’s Republic of ChinaTel +86-531- 88382548Fax +86-531-89631517Email guimeilin@sdu.edu.cnPurpose: Thymosin β-4(Tβ-4) is a macromolecular protein drug with potential for drug development in wound repair but is limited by the shortcomings of macromolecular protein, such as large volumes, poor membrane permeability, and unstable physicochemical characteristics. Ethosomes could enhance cell membrane fluidity and reduce epidermal membrane density to make macromolecular drugs through the stratum corneum into the deeper layers of the skin easily. Herein, we developed and characterized a novel transdermal delivery vehicle to load macromolecular protein peptides and use Tβ-4 as a model drug wrapped into ethosomes.Methods: We used the orthogonal method to optimize the formulation of the ethosome preparation prepared by the ethonal infusion method. Ethosomal gels were characterized by using different analytical methods. Transdermal release rate in vitro have been demonstrated in Franz diffusion cells and the efficacy of drug-loaded nanocarriers in vivo was investigated in a mouse model.Results: Optimized Tβ-4 ethosomal gels have good physicochemical properties. The drug amounts of the cumulative release in the ethosomal gel within 5 hours were 1.67 times that of the T-β4 gel in vitro release study, and the wound healing time of ethosomal gel group was only half of the T-β4 gel group in vivo pharmacokinetic study. Compared with the free drug group, the ethosome preparation not only promotes the percutaneous absorption process of the macromolecular protein drugs but also shortened wound recovery time.Conclusion: Hence, we provide a possible good design for ethosomal gel system that can load macromolecular protein peptide drugs to achieve transdermal drug administration, promoting the percutaneous absorption of the drug and improving the effect.Keywords: ethosomes, transdermal drug delivery system, macromolecular protein drugs, skin wound healing

Kun Liu,1 Jingchun Zeng,2 Wenya Pei,3 Siyu Chen,1 Zhenke Luo,1 Liming Lu,4 Guohua Lin21The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou 510405, People’s Republic of China; 2Department of Acupuncture, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510405, People’s Republic of China; 3Department of Acupuncture, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510405, People’s Republic of China; 4Clinical Research and Data Center, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510405, People’s Republic of ChinaBackground: This study evaluates the reporting quality of randomized controlled trials (RCTs) on acupuncture use for the treatment of postherpetic neuralgia and explores related factors.Methods: The following six databases PubMed, Embase, Cochrane Library, VIP, CNKI, and SinoMed, were systematically searched from their inception to December 2018. RCTs using acupuncture as an intervention for postherpetic neuralgia were selected and incorporated in this study. The reporting quality was assessed based on the CONSORT statement and the STRICTA guidelines. Regression analyses were also conducted on pre-specified study characteristics searching for factors associated with reporting quality.Results: A total of 137 RCTs were included in this study. The CONSORT based median OQS was 12 (minimum 3, maximum 29). Of the items comprised in the statement, ten were sufficiently reported (reported in over 70% of trials). The remaining fifty-five items were poorly reported (reported by fewer than 5% of trials). The STRICTA based median OQS was 9 (minimum 2, maximum 15). The results showed that eight of the comprised items were well reported (reported in over 70% of trials), and only three were incompletely reported (reported in fewer than 20% of trials). Based on the CONSORT statement related analysis, a post-2010 publication (β coefficient 2.394, 95% confidence interval [CI] 1.168–3.620) and funding (β coefficient 4.456, 95% CI: 3.009–5.903) represented independent and significant predictors of a high overall reporting quality. However, only a funding source (β coefficient 1.305, 95% CI 0.219–2.391) was associated with an increased OQS based on STRICTA analysis.Conclusion: The findings indicated that RCTs on acupuncture for PHN generally had a sub-optimal reporting quality, a situation that improved for those published after 2010 or with funding sources. Therefore, rigorous adherence to the CONSORT statement and the STRICTA guidelines should be emphasized in future studies.Keywords: randomized controlled trials, acupuncture, postherpetic neuralgia, CONSORT, STRICTA

Wenya Pei,1 Jingchun Zeng,2 Liming Lu,3 Guohua Lin,2 Jingwen Ruan11Department of Acupuncture, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Acupuncture, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; 3Clinical Medical Center, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaBackground: Postherpetic neuralgia (PHN) refers to pain which remains after the healing of rashes from herpes zoster. Previous literatures have shown that acupuncture has potential benefits for PHN, but evidence remains lacking. Thus, we have performed a systematic review and meta-analysis to identify the effectiveness of acupuncture in the treatment of PHN.Methods: Six databases were searched for randomized controlled trials (RCTs) to assess the effects of acupuncture on PHN. After selecting the studies, extracting the data, and assessing study quality, meta-analysis was performed on several of the studies with RevMan 5.3. The GRADE (Grading of Recommendations Assessment Development and Evaluation) system was used to assess the overall quality of the evidence.Results: Acupuncture helps relieve pain intensity (standardized mean difference [SMD]: −1.78, 95% confidence interval [CI]: −2.36 to −1.21). For other intervention types, electroacupuncture (SMD: −1.28, 95% CI: −2.51 to −0.05), fire needle (SMD: −2.23, 95% CI: −2.62 to −1.84), bloodletting and cupping (SMD: −2.46, 95% CI: −2.95 to −1.97) have better effects on pain intensity relief. To date, no study has reported on the onset of pain relief time. The Hamilton Anxiety Scale score (SMD: −18.94, 95% CI: −37.37 to −0.52) was lower for the acupuncture group than for the control group. It was also found that acupuncture can improve quality of life (QOL) (SMD: 3.78, 95% CI: 2.50 to 5.06). The quality of evidence for acupuncture for PHN pain intensity was moderate according to the GRADE system.Conclusion: Acupuncture may reduce pain intensity, relieve anxiety and improve quality of life in patients with PHN. Further randomized trials with larger sample sizes and of higher methodological quality are needed to confirm these results.Keywords: acupuncture, postherpetic neuralgia, systematic review

Dong-Ping Li,1,* Ying-Ling Chen,1,* Hong-Yue Jiang,1,* Yun Chen,1 Xiao-Qing Zeng,1 Li-Li Xu,1 Yang Ye,2 Chang-Qiang Ke,2 Ge Lin,3 Ji-Yao Wang,1,4 Hong Gao1,41Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2State Key Laboratory of Drug Research & Natural Products Chemistry Department, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Pudong, People’s Republic of China; 3School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR; 4Evidance-based Medicine Center of Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this work Purpose: To investigate the mitochondria-related mechanism of Gynura segetum (GS)-induced apoptosis and the protective effect of phosphocreatine (PCr), a mitochondrial respiration regulator.Methods: First, the mechanism was explored in human hepatocyte cell line. The mitochondrial oxidative stress was determined by fluorescence assay. The level of sirtuin 3 (SIRT3), acetylated superoxide dismutase 2 (Ac-SOD2), SOD2, and apoptosis were detected by Western blotting. Mito-TEMPO and cell lines of viral vector-mediated overexpression of SIRT3 and SIRT3H248Y, were used to further verify the mechanism of GS-induced apoptosis. GS-induced liver injury mice models were built by GS through intragastric administration and interfered by PCr through intraperitoneal injection. A total of 30 C57BL/6J mice were assigned to 5 groups and treated with either saline, PCr (100 mg/kg), GS (30 g/kg), or PCr (50 or 100 mg/kg)+GS (30 g/kg). Liver hematoxylin and eosin (HE) staining, immunohistochemical analysis, and blood biochemical evaluation were performed.Results: GS induced hepatocyte apoptosis and elevated levels of mitochondrial ROS in L-02 cells. The expression of SIRT3 was decreased. Downregulation of SIRT3 was associated with increased levels of Ac-SOD2, which is the inactivated enzymatic form of SOD2. Conversely, when overexpressing SIRT3 in GS-treated cells, SOD2 activity was restored, and mitochondrial ROS levels and hepatocyte apoptosis declined. Upon administration of PCr to GS-treated cells, they exhibited a significant upregulation of SIRT3 and were protected against apoptosis. In animal experiments, serum ALT level and mitochondrial ROS of the mice treated with GS and 50 mg/kg PCr were significantly attenuated compared with only GS treated. The changes in SIRT3 expression were also consistent with the in vitro results. In addition, immunohistochemical analysis of the mouse liver showed that Ac-SOD2 was decreased in the PCr and GS co-treated group compared with GS treated group.Conclusion: GS caused liver injury by dysregulating mitochondrial ROS generation via a SIRT3-SOD2 pathway. PCr is a potential agent to treat GS-induced liver injury by mitochondrial protection.Keywords: Gynura segetum, apoptosis, mitochondrial, ROS, SIRT3, phosphocreatine

Yongchu Sun,1 Huan Lin,1 Song Qu,1,2 Ling Li,1,2 Kaihua Chen,1 Binbin Yu,1,2 Guoxiang Lin,2 Fangzhu Wan,1 Xiaodong Zhu1–31Department of Radiation Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, People’s Republic of China; 2Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Ministry of Education, Nanning, Guangxi, People’s Republic of China; 3Department of Oncology, Affiliated Wuming Hospitalof Guangxi Medical University, , Nanning, Guangxi 530019, People’s Republic of ChinaObjective: CD166 is known as a tumor stem cell specific marker, associating with tumor metastasis. The purpose of this study was to further discuss CD166 gene on cell proliferation, invasion, metastasis, and the epithelial-mesenchymal transition (EMT) in CNE-2R cell line of nasopharyngeal carcinoma (NPC).Materials and methods: CNE-2R cells were transfected with lentivirus CD166-shRNA, and quantitative reverse transcription polymerase chain reaction (RT-qPCR), and Western blotting were used to confirm the silencing effects. The wound healing test and transwell test were carried out to assess cell invasive and migratory abilities in vitro. With the establishment of xenograft nude mouse model, Western blotting and immunohistochemistry were undertaken to detect the expression level of E-cadherin, N-cadherin, and vimentin. In vivo metastasis detection was carried out by injecting tumor cells into nude mice via the tail vein.Results: The invasive and migratory abilities of CNE-2R cells were significantly reduced after CD166 was downregulated. In addition, silencing of CD166 of CNE-2R cells increased the expression of E-cadherin, while down-regulated the expression of N-cadherin and vimentin. Immunohistochemistry of tumors showed consistent results with in-situ tumor formation experiment. Additionally, the growth of transplanted tumor was inhibited. In addition, in vivo metastasis test proved that knockdown of CD166 suppressed pulmonary metastasis and liver metastasis according to hematoxylin and eosin (H&E) staining. Expression of E-cadherin increased, while expression of N-cadherin and vimentin decreased, as revealed by Western blotting of metastatic lung tumors.Conclusion: Silencing of CD166 in CNE-2R cells evidently inhibited proliferation, invasion, metastasis, and EMT process in vivo and in vitro.Keywords: nasopharyngeal carcinoma, CD166, metastasis, EMT

Improved blood tests assessing the functional status of rare gluten-specific CD4+ T cells are needed to effectively monitor experimental therapies for coeliac disease (CD). Our aim was to develop a simple, but highly sensitive cytokine release assay (CRA) for gluten-specific CD4+ T cells that did not require patients to undergo a prior gluten challenge, and would be practical in large, multi-centre clinical trials. We developed an enhanced CRA and used it in a phase 2 clinical trial (“RESET CeD”) of Nexvax2, a peptide-based immunotherapy for CD. Two participants with treated CD were assessed in a pilot study prior to and six days after a 3-day gluten challenge. Dye-dilution proliferation in peripheral blood mononuclear cells (PBMC) was assessed, and IL-2, IFN-γ and IL-10 were measured by multiplex electrochemiluminescence immunoassay (ECL) after 24-hour gluten-peptide stimulation of whole blood or matched PBMC. Subsequently, gluten-specific CD4+ T cells in blood were assessed in a subgroup of the RESET CeD Study participants who received Nexvax2 (maintenance dose 900 μg, n = 12) or placebo (n = 9). The pilot study showed that gluten peptides induced IL-2, IFN-γ and IL-10 release from PBMCs attributable to CD4+ T cells, but the PBMC CRA was substantially less sensitive than whole blood CRA. Only modest gluten peptide-stimulated IL-2 release could be detected without prior gluten challenge using PBMC. In contrast, whole blood CRA enabled detection of IL-2 and IFN-γ before and after gluten challenge. IL-2 and IFN-γ release in whole blood required more than 6 hours incubation. Delay in whole blood incubation of more than three hours from collection substantially reduced antigen-stimulated IL-2 and IFN-γ secretion. Nexvax2, but not placebo treatment in the RESET CeD Study was associated with significant reductions in gluten peptide-stimulated whole blood IL-2 and IFN-γ release, and CD4+ T cell proliferation. We conclude that using fresh whole blood instead of PBMC substantially enhances cytokine secretion stimulated by gluten peptides, and enables assessment of rare gluten-specific CD4+ T cells without requiring CD patients to undertake a gluten challenge. Whole blood assessment coupled with ultra-sensitive cytokine detection shows promise in the monitoring of rare antigen-specific T cells in clinical studies.