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1.
Front Public Health ; 12: 1353415, 2024.
Article in English | MEDLINE | ID: mdl-38966699

ABSTRACT

Background: The protective effectiveness provided by naturally acquired immunity against SARS-CoV-2 reinfection remain controversial. Objective: To systematically evaluate the protective effect of natural immunity against subsequent SARS-CoV-2 infection with different variants. Methods: We searched for related studies published in seven databases before March 5, 2023. Eligible studies included in the analysis reported the risk of subsequent infection for groups with or without a prior SARS-CoV-2 infection. The primary outcome was the overall pooled incidence rate ratio (IRR) of SARS-CoV-2 reinfection/infection between the two groups. We also focused on the protective effectiveness of natural immunity against reinfection/infection with different SARS-CoV-2 variants. We used a random-effects model to pool the data, and obtained the bias-adjusted results using the trim-and-fill method. Meta-regression and subgroup analyses were conducted to explore the sources of heterogeneity. Sensitivity analysis was performed by excluding included studies one by one to evaluate the stability of the results. Results: We identified 40 eligible articles including more than 20 million individuals without the history of SARS-CoV-2 vaccination. The bias-adjusted efficacy of naturally acquired antibodies against reinfection was estimated at 65% (pooled IRR = 0.35, 95% CI = 0.26-0.47), with higher efficacy against symptomatic COVID-19 cases (pooled IRR = 0.15, 95% CI = 0.08-0.26) than asymptomatic infection (pooled IRR = 0.40, 95% CI = 0.29-0.54). Meta-regression revealed that SARS-CoV-2 variant was a statistically significant effect modifier, which explaining 46.40% of the variation in IRRs. For different SARS-CoV-2 variant, the pooled IRRs for the Alpha (pooled IRR = 0.11, 95% CI = 0.06-0.19), Delta (pooled IRR = 0.19, 95% CI = 0.15-0.24) and Omicron (pooled IRR = 0.61, 95% CI = 0.42-0.87) variant were higher and higher. In other subgroup analyses, the pooled IRRs of SARS-CoV-2 infection were statistically various in different countries, publication year and the inclusion end time of population, with a significant difference (p = 0.02, p < 0.010 and p < 0.010), respectively. The risk of subsequent infection in the seropositive population appeared to increase slowly over time. Despite the heterogeneity in included studies, sensitivity analyses showed stable results. Conclusion: Previous SARS-CoV-2 infection provides protection against pre-omicron reinfection, but less against omicron. Ongoing viral mutation requires attention and prevention strategies, such as vaccine catch-up, in conjunction with multiple factors.


Subject(s)
COVID-19 , Reinfection , SARS-CoV-2 , Humans , COVID-19/prevention & control , COVID-19/epidemiology , COVID-19/immunology , SARS-CoV-2/immunology , Immunity, Innate
2.
IEEE Trans Vis Comput Graph ; 30(5): 2464-2473, 2024 May.
Article in English | MEDLINE | ID: mdl-38437126

ABSTRACT

Redirected walking (RDW) enables users to walk naturally within a virtual environment that is larger than the physical environment. Recently, several artificial potential field (APF) and alignment-based redirected controllers have been developed and have been demonstrated to significantly outperform conventional controllers. APF Steer-to-Gradient (APF-S2G) and APF Redirected Walking (APF-RDW) utilize the negative gradient and the total force vector, respectively, which are localized to the user's position. These vectors usually point towards the opposite wall when the user is in corridors, resulting in frequent resets within those regions. This paper introduces the APF Steer-to-Target (APF-S2T), a redirected controller that first finds the target sample point with the lowest score in the user's walkable area in both physical and virtual environments. The score of a sample point is determined by the APF value at the point and the distance from the user's position. The direction from the user's position to the target point is then used as the steering direction for setting RDW gains. We conducted a simulation-based evaluation to compare APF-S2T, APF-S2G, APF-RDW, Visibility Polygon-based alignment (Vis.-Poly.) and Alignment-Optimized controllers in terms of the number of resets and the average distance between resets. The results indicated that APF-S2T significantly outperformed the state-of-the-art controllers.

3.
Org Lett ; 26(8): 1694-1698, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38360059

ABSTRACT

Synthesis of benzo[c]cinnolinium salts by copper(II)-promoted or electrochemical oxidation of 2-azobiaryls is described. A variety of diversely functionalized benzo[c]cinnolinium salts were easily constructed by this strategy with excellent functional group tolerance and high efficiency. An interesting fluorescence centered at 571 nm is revealed by a benzo[c]cinnolinium salt with electron push-pull substitutions. The mechanism is proposed to go through single-electron transfer driven by oxidant and intramolecular cyclization via nucleophilic addition, followed by an anion exchange.

4.
Environ Res ; 248: 118409, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38311203

ABSTRACT

A huge production of waste activated sludge (WAS) has been a burden for wastewater treatment plants (WWTPs) with high disposal cost and little benefit back to wastewater purification. The short-chain fatty acids (SCFAs) produced by a short-term acidogenic fermentation of WAS before methane production have been proven to be a high-quality carbon source available for microbial denitrification process. The dual purpose of full recovery of fermentation liquid products and facilitating disposal of residual solid waste necessitate an efficient solid-liquid separation process of short-term fermentation liquid. The transformation and loss of various soluble carbon sources between solid and liquid are very important issues for carbon recovery efficiency when combining short-term fermentation and sludge dewatering in WWTPs. Here we testified the three conventional preconditioning coagulants, Polyferric Sulfate (PFS), Poly Aluminum Chloride (PAC) and Polyacrylamide (PAM), to improve the efficiency of subsequent solid-liquid separation. The results show that conversion yield of SCFAs in the liquid phase of sludge after short-term fermentation was 195 mg COD/g VSS, when using the coagulants PFS, PAC, and PAM for recovery, the recovery ratio was 79.5%, 82.0%, and 85.9%, respectively, while the dewaterability could be improved after preconditioning short-term fermentation sludge. The complexation of Al3+/Fe3+ in metal coagulants with carboxyl groups of SCFA demonstrated by Density Functional Theory calculation led to small part of soluble carbons co-migration to the solid phase, mainly a loss of high molecular weight organic compounds (carbohydrate, proteins, humic acids), while the application of PAM had little impact on carbon recovery. Economic calculations further showed PAM preconditioning short-term fermentation liquid of WAS could achieve higher recovery benefits.


Subject(s)
Sewage , Water Purification , Fermentation , Carbon , Fatty Acids, Volatile
5.
IEEE Trans Vis Comput Graph ; 29(11): 4556-4566, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37788204

ABSTRACT

Redirected walking allows users to naturally locomote within virtual environments that are larger than or different in layout from the physically tracked space. In this paper, we proposed novel optimization-driven alignment-based and Artificial Potential Field (APF) redirected walking controllers, as well as an integrated version of the two. The first two controllers employ objective functions of one variable, which is the included angle between the user's heading vector and the target vector originating from the user's physical position. The optimized angle represents the physical cell that is best aligned with the virtual cell or the target vector on which the designated point has the minimum APF value. The derived optimized angle is used to finely set RDW gains. The two objective functions can be optimized simultaneously, leading to an integrated controller that is potentially able to take advantage of the alignment-based controller and APF-based controller. Through extensive simulation-based studies, we found that the proposed alignment-based and integrated controllers significantly outperform the state-of-the-art controllers and the proposed APF based controller in terms of the number of resets. Furthermore, the proposed alignment controller and integrated controller provide a more uniform likelihood distribution across distance between resets, as compared to the other controllers.

6.
J Sports Sci ; 41(12): 1179-1186, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37732628

ABSTRACT

The impact of mitral valve prolapse (MVP) and mitral regurgitation (MR) on physical performance has not been examined. Of 1,808 physically fit Asian military males, we compared the physical fitness between 62 subjects with MVP (MVP(+)) and 1,311 age- and anthropometrics-matched controls from the 1,746 participants without MVP (MVP(-)). MVP and MR grade were defined based on the American Society of Echocardiography criteria. Aerobic endurance capacity was evaluated by a 3000-m run and muscular endurance capacity was separately evaluated by 2-min sit-ups and 2-min push-ups. Analysis of covariance was used to determine the difference between groups. As compared to the MVP(-), the MVP(+) completed the 3000-m run test faster (839.2 ± 65.3 sec vs. 866.6 ± 86.8 sec, p = 0.019), but did fewer push-ups (41.3 ± 3.92 vs. 48.0 ± 10.1, p = 0.02) and similar sit-ups within 2 min. Of the MVP(+), those with any MR (trivial, mild or moderate) completed the 3000-m run test faster than those without MR (830.6 ± 61.7 sec vs. 877.2 ± 61.7 sec, p = 0.02). Our findings suggest that in physically active Asian military males, the MVP(+) may have greater aerobic endurance capacity but lower muscular endurance capacity than the MVP(-). The presence of MR may play a role for the MVP(+) to have greater aerobic endurance capacity.

7.
Environ Sci Ecotechnol ; 14: 100235, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36660739

ABSTRACT

Carbon cycle regulation and greenhouse gas (GHG) emission abatement within wastewater treatment plants (WWTPs) can theoretically improve sustainability. Currently, however, large amounts of external carbon sources used for deep nitrogen removal and waste sludge disposal aggravate the carbon footprint of most WWTPs. In this pilot-scale study, considerable carbon was preliminarily recovered from primary sludge (PS) through short-term (five days) acidogenic fermentation and subsequently utilized on-site for denitrification in a wool processing industrial WWTP. The recovered sludge-derived carbon sources were excellent electron donors that could be used as additional carbon supplements for commercial glucose to enhance denitrification. Additionally, improvements in carbon and nitrogen flow further contributed to GHG emission abatement. Overall, a 9.1% reduction in sludge volatile solids was achieved from carbon recovery, which offset 57.4% of external carbon sources, and the indirect GHG emissions of the target industrial WWTP were reduced by 8.05%. This study demonstrates that optimizing the allocation of carbon mass flow within a WWTP has numerous benefits.

8.
Chinese Journal of Trauma ; (12): 265-270, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-992597

ABSTRACT

Objective:To explore the effect of cluster nursing in robot-assisted surgery for the treatment of reducible atlantoaxial dislocation.Methods:A retrospective cohort study was conducted to analyze the clinical data of 41 patients with reducible atlantoaxial dislocation treated by robot-assisted surgery in Honghui Hospital affiliated to Xi′an Jiaotong University from January 2019 to December 2021, including 28 males and 13 females; aged 18-79 years [(45.2±10.3)years]. Ninteen patients received cluster nursing (cluster nursing group), with operating room nursing team set up on the basis of routine nursing and performed cluster nursing in line with evidence-based medicine. Twenty-two patients received routine nursing (routine nursing group). The operation time, intraoperative blood loss, frequency of intraoperative C-arm fluoroscopy, time of drainage tube placement and chief surgeon′s satisfaction for nursing were compared between the two groups. The degree of pain was evaluated by pain numerical score (NRS) at 12 hours, 24 hours, 48 hours, 72 hours, 1 month and 3 months after operation and at the last follow-up. The neck disability index (NDI) was assessed at 1 day before operation, 1 month after operation, 3 months after operation and at the last follow-up. The complications were observed.Results:All patients were followed up for 12-18 months [(16.7±3.7)months]. The operation time, intraoperative blood loss, frequency of C-arm fluoroscopy and time of drainage tube placement in cluster nursing group were (82.9±10.4)minutes, (105.9±11.8)ml, (3.8±0.6)times and (1.5±0.4)days, while those in routine nursing group were (125.7±12.8)minutes, (208.4±13.8)ml, (9.7±2.3)times and (3.6±0.6)days, respectively (all P<0.01). The chief surgeon′s satisfaction for nursing was 94.7% (18/19) in cluster nursing group and was 68.2% (15/22) in routine nursing group ( P<0.05). The NRS in cluster nursing group was (6.2±0.4)points, (6.0±0.7)points, (4.9±1.1)points, (2.7±0.5)points, (1.9±0.4)points, (1.8±0.4)points and (1.5±0.3)points at 12 hours, 24 hours, 48 hours, 72 hours, 1 month and 3 months after operation and at the last follow-up, while it was (7.6±0.6)points, (6.8±1.2)points, (5.8±1.5)points, (4.2±0.8)points, (3.4±0.7)points, (2.6±0.5)points and (2.2±0.5)points in routine nursing group ( P<0.05 or 0.01). There was no significant difference in the NDI between the two groups at 1 day before operation, but the NDI in cluster nursing group was 20.6±4.5, 14.6±2.8 and 10.7±2.5 at 1 month and 3 months after operation and at the last follow-up, while it was 26.9±4.1, 18.7±3.3 and 13.7±1.7 in routine nursing group (all P<0.01). There was no hematoma, infection or implant-related complications in both groups .Conclusion:For robot-assisted surgery in the treatment of reducible atlantoaxial dislocation, cluster nursing is associated with shortened operation time and time of drainage tube placement, decreased intraoperative blood loss and frequency of intraoperative fluoroscopy, increased chief surgeon′s satisfaction for nursing, reduced pain and accelerated functional recovery.

9.
Chinese Journal of Epidemiology ; (12): 677-682, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-985546

ABSTRACT

HIV cluster detection and response (CDR) is a critical strategy to end the HIV epidemic by offering information to identify prevention and care services gaps. The risk metrics for HIV clusters can be classified into three groups: growth-based metrics, characteristic-based metrics, and phylogeny-based metrics. When identifying HIV risk clusters, the public health response can reach people in the affected networks, including people with undiagnosed HIV, people with diagnosed HIV who might not be accessing HIV care or other services, and people without HIV who would benefit from prevention services. To provide references for HIV precise prevention in China, we summarized the risk metrics and the intervention measures for CDR.


Subject(s)
Humans , HIV Infections/prevention & control , Acquired Immunodeficiency Syndrome/epidemiology , Public Health , Epidemics/prevention & control , China/epidemiology
10.
Pathologie (Heidelb) ; 43(Suppl 1): 25-30, 2022 Aug.
Article in English | MEDLINE | ID: mdl-36094651

ABSTRACT

Anaplastic large cell lymphoma (ALCL) is a CD30-positive non-Hodgkin's T­cell lymphoma. Despite the implementation of CD30 antibody-drug conjugate-targeted therapy into front-line treatment regimens, the prognosis of some subtypes of the disease remains unsatisfactory. In the relapsed/refractory setting, effective second-line treatment options are still lacking. However, it has been reported that blockade of direct downstream targets of activator protein­1 (AP-1) transcription factors, which are highly dysregulated in ALCL, results in complete and sustained remission in late-stage relapsed/refractory anaplastic lymphoma kinase (ALK)-positive ALCL patients. Moreover, it has been identified that involvement of the BATF3/AP­1 module promotes lymphomagenesis via oncogenic BATF3/IL-2/IL-2R signaling through hyperphosphorylation of ERK1/2, STAT1, and STAT5 in ALCL cells regardless of their ALK status. Therefore, targeting BATF3/IL-2/IL-2R signaling may represent a novel therapeutic alternative for ALCL patients.


Subject(s)
Lymphoma, Large-Cell, Anaplastic , Humans , Lymphoma, Large-Cell, Anaplastic/drug therapy , Interleukin-2/therapeutic use , Receptor Protein-Tyrosine Kinases/therapeutic use , Anaplastic Lymphoma Kinase/therapeutic use , Transcription Factor AP-1/therapeutic use , Interleukin-2 Receptor alpha Subunit/therapeutic use
11.
Acta Crystallogr E Crystallogr Commun ; 78(Pt 6): 590-593, 2022 Jun 01.
Article in English | MEDLINE | ID: mdl-36072156

ABSTRACT

The crystal of the title compound, C60H38N2O2, which crystallizes in the monoclinic space group P21/n, was obtained by thermal evaporation of a 1:1 di-chloro-methane and hexa-nes solution of the pure compound. The crystal structure is stabilized by π-π inter-actions between benzo[def]carbazole moieties and carbon-yl-carbonyl inter-actions between the two acetyl groups.

12.
Microorganisms ; 10(9)2022 Aug 27.
Article in English | MEDLINE | ID: mdl-36144331

ABSTRACT

Aim: To develop a reproducible biofilm model consisting of Enterococcus faecalis (E. faecalis) and Porphyromonas gingivalis (P. gingivalis) and to evaluate the interaction between the two bacterial species. Methodology: E. faecalis and P. gingivalis were grown in mono-culture, sequential, and co-culture models for 96 h in a 96-well polystyrene microtiter plate under both aerobic and anaerobic conditions separately. The viability of the two bacterial species in the biofilms was quantified by polymerase chain reaction (qPCR). Biofilm thickness and protein contents were measured using confocal laser scanning microscopy (CLSM). Two-way analysis of variance (ANOVA) was performed to analyze cell viability and biofilm thickness among different culture models cultivated under either aerobic or anaerobic conditions. The level of significance was set at p < 0.05. Results: Different culture models tested did not show any significant difference between the viable cell counts of both E. faecalis and P. gingivalis cultivated under aerobic and anaerobic conditions (p > 0.05). Biofilm was significantly thicker (p < 0.05) in the co-culture models compared to the mono-culture and sequential models. Protein contents in the biofilms were more pronounced when both bacterial species were co-cultured under aerobic conditions. Conclusions: E. faecalis appeared to shield P. gingivalis and support its continued growth in oxic (aerobic) conditions. The co-culture model of E. faecalis and P. gingivalis produced a significantly thicker biofilm irrespective of the presence or absence of oxygen, while increased protein contents were only observed in the presence of oxygen.

13.
Front Pharmacol ; 13: 804566, 2022.
Article in English | MEDLINE | ID: mdl-36034817

ABSTRACT

Potentially inappropriate prescribing (PIP), including potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs), is a major risk factor for adverse drug reactions (ADRs). Establishing a risk warning model for PIP to screen high-risk patients and implementing targeted interventions would significantly reduce the occurrence of PIP and adverse drug events. Elderly patients with cardiovascular disease hospitalized at the Sichuan Provincial People's Hospital were included in the study. Information about PIP, PIM, and PPO was obtained by reviewing patient prescriptions according to the STOPP/START criteria (2nd edition). Data were divided into a training set and test set at a ratio of 8:2. Five sampling methods, three feature screening methods, and eighteen machine learning algorithms were used to handle data and establish risk warning models. A 10-fold cross-validation method was employed for internal validation in the training set, and the bootstrap method was used for external validation in the test set. The performances were assessed by area under the receiver operating characteristic curve (AUC), and the risk warning platform was developed based on the best models. The contributions of features were interpreted using SHapley Additive ExPlanation (SHAP). A total of 404 patients were included in the study (318 [78.7%] with PIP; 112 [27.7%] with PIM; and 273 [67.6%] with PPO). After data sampling and feature selection, 15 datasets were obtained and 270 risk warning models were built based on them to predict PIP, PPO, and PIM, respectively. External validation showed that the AUCs of the best model for PIP, PPO, and PIM were 0.8341, 0.7007, and 0.7061, respectively. The results suggested that angina, number of medications, number of diseases, and age were the key factors in the PIP risk warning model. The risk warning platform was established to predict PIP, PIM, and PPO, which has acceptable accuracy, prediction performance, and potential clinical application perspective.

14.
ACS Appl Mater Interfaces ; 14(34): 39109-39119, 2022 Aug 31.
Article in English | MEDLINE | ID: mdl-35976775

ABSTRACT

The device efficiency of PM6:Y6-based nonfullerene organic solar cells is fast advanced recently. To maintain organic solar cells (OSCs) with high power conversion efficiency over 16% in long-term operation, however, remains a challenge. Here, a novel non-volatile additive, an open-cage [60]fullerene (8OC60Me), is incorporated into PM6:Y6-based OSCs for high-performance with high durability. With optimized addition of 1.0 wt % 8OC60Me, the PCE value of PM6:Y6/8OC60Me OSCs can be promoted to 16.5% from 15.0%. Most strikingly, such a high PCE performance can maintain nearly 100% for over 500 h at room temperature; at an elevated operation temperature of 80 °C, the PCE can be stabilized above 15.0% after 45 h of operation. Grazing incidence small- and wide- angle X-ray scattering studies reveal improved orientation and crystallinity of Y6 in a fractal-like network structure of PM6 in PM6:Y6/8OC60Me films under in situ annealing, parallel to the enhanced electron mobility. Analysis of charge distributions lines up possible van der Waals interaction between the thienyl/carbonyl moiety of 8OC60Me and difluorophenyl-based FIC-end groups of Y6. This result is of great contrast to those devices with the best-selling PC61BM as the additives─8OC60Me might be of interest to be incorporated into future Y6-based OSCs for concomitantly improved PCE and excellent stability.

15.
Leukemia ; 36(8): 2050-2063, 2022 08.
Article in English | MEDLINE | ID: mdl-35676454

ABSTRACT

We recently reported that miR-146a is differentially expressed in ALK+ and ALK- anaplastic large cell lymphoma (ALCL). In this study, the downstream targets of miR-146a in ALK+ ALCL were investigated by transcriptome analysis, identifying CD147 as potential target gene. Because CD147 is differentially expressed in ALK+ ALCL versus ALK- ALCL and normal T cells, this gene emerged as a strong candidate for the pathogenesis of this tumor. Here we demonstrate that CD147 is a direct target of miR-146 and contributes to the survival and proliferation of ALK+ ALCL cells in vitro and to the engraftment and tumor growth in vivo in an ALK+ ALCL-xenotransplant mouse model. CD147 knockdown in ALK+ ALCL cells resulted in loss of monocarboxylate transporter 1 (MCT1) expression, reduced glucose consumption and tumor growth retardation, as demonstrated by [18F]FDG-PET/MRI analysis. Investigation of metabolism in vitro and in vivo supported these findings, revealing reduced aerobic glycolysis and increased basal respiration in CD147 knockdown. In conclusion, our findings indicate that CD147 is of vital importance for ALK+ ALCL to maintain the high energy demand of rapid cell proliferation, promoting lactate export, and tumor growth. Furthermore, CD147 has the potential to serve as a novel therapeutic target in ALK+ ALCL, and warrants further investigation.


Subject(s)
Anaplastic Lymphoma Kinase , Basigin , Energy Metabolism , Lymphoma, Large-Cell, Anaplastic , MicroRNAs , Anaplastic Lymphoma Kinase/genetics , Anaplastic Lymphoma Kinase/metabolism , Animals , Basigin/genetics , Basigin/metabolism , Cell Line, Tumor , Energy Metabolism/genetics , Energy Metabolism/physiology , Gene Expression Regulation, Neoplastic , Lymphoma, Large-Cell, Anaplastic/genetics , Lymphoma, Large-Cell, Anaplastic/metabolism , Mice , MicroRNAs/genetics , MicroRNAs/metabolism , Receptor Protein-Tyrosine Kinases/genetics , Receptor Protein-Tyrosine Kinases/metabolism
16.
JBMR Plus ; 6(5): e10623, 2022 May.
Article in English | MEDLINE | ID: mdl-35509638

ABSTRACT

The expression of microRNAs (miRNAs) is dysregulated in many types of cancers including osteosarcoma (OS) due to genetic and epigenetic alterations. Among these, miR-34c, an effector of tumor suppressor P53 and an upstream negative regulator of Notch signaling in osteoblast differentiation, is dysregulated in OS. Here, we demonstrated a tumor suppressive role of miR-34c in OS progression using in vitro assays and in vivo genetic mouse models. We found that miR-34c inhibits the proliferation and the invasion of metastatic OS cells, which resulted in reduction of the tumor burden and increased overall survival in an orthotopic xenograft model. Moreover, the osteoblast-specific overexpression of miR-34c increased survival in the osteoblast specific p53 mutant OS mouse model. We found that miR-34c regulates the transcription of several genes in Notch signaling (NOTCH1, JAG1, and HEY2) and in p53-mediated cell cycle and apoptosis (CCNE2, E2F5, E2F2, and HDAC1). More interestingly, we found that the metastatic-free survival probability was increased among a patient cohort from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) OS, which has lower expression of direct targets of miR-34c that was identified in our transcriptome analysis, such as E2F5 and NOTCH1. In conclusion, we demonstrate that miR-34c is a tumor suppressive miRNA in OS progression in vivo. In addition, we highlight the therapeutic potential of targeting miR-34c in OS. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

18.
Nat Commun ; 12(1): 5577, 2021 09 22.
Article in English | MEDLINE | ID: mdl-34552066

ABSTRACT

Anaplastic large cell lymphoma (ALCL), an aggressive CD30-positive T-cell lymphoma, comprises systemic anaplastic lymphoma kinase (ALK)-positive, and ALK-negative, primary cutaneous and breast implant-associated ALCL. Prognosis of some ALCL subgroups is still unsatisfactory, and already in second line effective treatment options are lacking. To identify genes defining ALCL cell state and dependencies, we here characterize super-enhancer regions by genome-wide H3K27ac ChIP-seq. In addition to known ALCL key regulators, the AP-1-member BATF3 and IL-2 receptor (IL2R)-components are among the top hits. Specific and high-level IL2R expression in ALCL correlates with BATF3 expression. Confirming a regulatory link, IL-2R-expression decreases following BATF3 knockout, and BATF3 is recruited to IL2R regulatory regions. Functionally, IL-2, IL-15 and Neo-2/15, a hyper-stable IL-2/IL-15 mimic, accelerate ALCL growth and activate STAT1, STAT5 and ERK1/2. In line, strong IL-2Rα-expression in ALCL patients is linked to more aggressive clinical presentation. Finally, an IL-2Rα-targeting antibody-drug conjugate efficiently kills ALCL cells in vitro and in vivo. Our results highlight the importance of the BATF3/IL-2R-module for ALCL biology and identify IL-2Rα-targeting as a promising treatment strategy for ALCL.


Subject(s)
Basic-Leucine Zipper Transcription Factors/genetics , Lymphoma, Large-Cell, Anaplastic/genetics , Receptors, Interleukin-2/genetics , Repressor Proteins/genetics , Animals , Basic-Leucine Zipper Transcription Factors/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Gene Expression Regulation, Neoplastic , Humans , Immunoconjugates/pharmacology , Interleukin-15/pharmacology , Interleukin-2/pharmacology , Interleukin-2 Receptor alpha Subunit/genetics , Interleukin-2 Receptor alpha Subunit/immunology , Interleukin-2 Receptor alpha Subunit/metabolism , Ki-1 Antigen/genetics , Ki-1 Antigen/metabolism , Lymphoma, Large-Cell, Anaplastic/drug therapy , Lymphoma, Large-Cell, Anaplastic/metabolism , Lymphoma, Large-Cell, Anaplastic/pathology , Mice , Receptors, Interleukin-2/immunology , Receptors, Interleukin-2/metabolism , Regulatory Sequences, Nucleic Acid , Repressor Proteins/metabolism , Signal Transduction/drug effects , Xenograft Model Antitumor Assays
19.
Sci Rep ; 11(1): 2719, 2021 02 01.
Article in English | MEDLINE | ID: mdl-33526804

ABSTRACT

The prevalence of mitral valve prolapse (MVP) among middle- and older-aged individuals is estimated to be 2-4% in Western countries. However, few studies have been conducted among Asian individuals and young adults. This study included a sample of 2442 consecutive military adults aged 18-39 years in Hualien, Taiwan. MVP was defined as displacement of the anterior or posterior leaflet of the mitral valve to the mid portion of the annular hinge point > 2 mm in the parasternal long-axis view of echocardiography. Cardiac chamber size and wall thickness were measured based on the latest criteria of the American Society of Echocardiography. The clinical features of participants with MVP and those without MVP were compared using a two-sample t test, and the cardiac structures were compared using analysis of covariance with adjustment for body surface area (BSA). Eighty-two participants were diagnosed with MVP, and the prevalence was 3.36% in the overall population. Compared with those without MVP, participants with MVP had a lower body mass index (kg/m2) (24.89 ± 3.70 vs. 23.91 ± 3.45, p = 0.02) and higher prevalence of somatic symptoms related to exercise (11.0% vs. 4.9%, p = 0.02) and systolic click in auscultation (18.3% vs. 0.6%, p < 0.01). In addition, participants with MVP had greater left ventricular mass (gm) and smaller right ventricular wall thickness (mm) and dimensions (mm) indexed by BSA than those without MVP (149.12 ± 35.76 vs. 155.38 ± 36.26; 4.66 ± 0.63 vs. 4.40 ± 0.68; 26.57 ± 3.99 vs. 25.41 ± 4.35, respectively, all p-values < 0.01). In conclusion, the prevalence and clinical features of MVP in military young adults in Taiwan were in line with those in Western countries. Whether the novel MVP phenotype found in this study has any pathological meaning needs further investigation.


Subject(s)
Military Personnel , Mitral Valve Prolapse/epidemiology , Mitral Valve/diagnostic imaging , Adolescent , Adult , Echocardiography , Female , Humans , Male , Mitral Valve Prolapse/diagnostic imaging , Prevalence , Taiwan/epidemiology , Young Adult
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