Publications by authors named "Tong Zheng"

146 Publications

Tim-4 maintains adipose tissue homeostasis by orchestrating M2 macrophage polarization via NF-κB pathway.

Immunology 2022 Jul 31. Epub 2022 Jul 31.

Key Laboratory for Experimental Teratology of Ministry of Education, Shandong Key Laboratory of Infection and Immunity, and Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P. R. China.

Obesity is generally associated with low-grade inflammation. Adipose tissue macrophages (ATMs) orchestrate metabolic inflammation. The classical (M1-like) or alternative (M2-like) activation of ATMs is functionally coupled with the metabolic status of fat tissues. It has been found that T-cell immunoglobulin- and mucin-domain-containing molecule-4 (Tim-4) inhibits inflammation by regulating macrophages. However, the exact role of Tim-4 in macrophage polarization and obesity remains unknown. Here, we identified Tim-4 as a critical switch governing macrophage M1/M2 polarization and energy homeostasis. Tim-4 deletion led to spontaneous obesity in elder mice and promoted obesity severity of db/db mice. Obesity microenvironment enhanced the expression of Tim-4 in white adipose tissue (WAT) and ATMs. In vitro, we detected an increase in M1-like cells and decrease in M2-like cells in both peritoneal macrophages and bone marrow-derived macrophages from Tim-4 knockout mice. Mechanistically, we demonstrated that Tim-4 promoted M2-like macrophages polarization via suppressing nuclear factor kappa B (NF-κB) signaling pathway. In addition, we found that Tim-4 promoted TLR4 internalization, which might contribute to regulation of NF-κB signaling. Collectively, these results indicated that Tim-4 maintained adipose tissue homeostasis by regulating macrophage polarization via NF-κB pathway, which would provide a new target for obesity intervention. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/imm.13555DOI Listing
July 2022

Correlations of magnetic resonance imaging classifications with preoperative functions among patients with refractory lateral epicondylitis.

BMC Musculoskelet Disord 2022 Jul 20;23(1):690. Epub 2022 Jul 20.

Sports Medicine Service, Beijing Jishuitan Hospital, No. 31, Xin Jie Kou East Street, Xi Cheng District, Beijing, China.

Background: To evaluate the correlations between three magnetic resonance imaging (MRI) classifications and preoperative function in patients with refractory lateral epicondylitis (LE).

Methods: We retrospectively reviewed patients with refractory LE who underwent arthroscopic treatment. Signal changes in the origin of the extensor carpi radialis brevis (ERCB) were evaluated based on three different MRI classification systems. Spearman's rank correlation analysis was used to analyse the correlation between each MRI classification and the preoperative functional and visual analogue scale (VAS). The lateral collateral ligament complex (LCL) in all patients was evaluated using both MRI and arthroscopy. The Mann-Whitney U test was used for the comparison of preoperative VAS and all functional scores between patients with refractory LE combined with LCL lesions, and those without.

Results: There were 51 patients diagnosed with refractory LE between June 2014 to December 2020, all of whom were included in this study. The patients included 32 women and 19 men with a mean age of 49.1 ± 7.6 years (range, 39-60 years). The average duration of symptoms was 21.1 ± 21.2 months (range, 6-120 months). The intra-observer agreements for Steinborn et al.'s classification were 77.9%, 76.0%, and 76.7%, respectively. The inter-observer reliabilities of the three classifications were 0.734, 0.751, and 0.726, respectively. The average intra-observer agreement for the diagnosis of abnormal LCL signal was 89.9%, with an overall weighted kappa value of 0.904. The false-positive rate was 50%, and the false-negative rate was 48% for LCL evaluation on MRI. Spearman's rank correlation analysis did not find significant correlation between any of the three MRI classifications and preoperative VAS or any functional scores (all P > 0.05). There were no significant differences in the VAS and functional scores between patients with abnormal LCL signals on MRI and those without LCL lesions (all P > 0.05).

Conclusions: Preoperative MRI findings in patients with refractory LE cannot reflect the severity of functional deficiency. Preoperative MRI grading of the origin of the ERCB and preoperative MRI for LCL signal change cannot assist the surgical plan for the treatment of patients with refractory LE.
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http://dx.doi.org/10.1186/s12891-022-05651-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9297620PMC
July 2022

Legacy and alternative flame retardants in indoor dust from e-waste industrial parks and adjacent residential houses in South China: Variations, sources, and health implications.

Sci Total Environ 2022 Jul 13;845:157307. Epub 2022 Jul 13.

The Postgraduate Training Base of Jinzhou Medical University (South China Institute of Environmental Sciences, Ministry of Ecology and Environment), Guangzhou 510530, China; State Environmental Protection Key Laboratory of Environmental Pollution Health Risk Assessment, South China Institute of Environmental Sciences, Ministry of Ecology and Environment, Guangzhou 510530, China. Electronic address:

Many studies have elucidated health concerns of informal e-waste recycling activities, yet few has evaluated the effectiveness of the regulations as well as the human exposure risks to adjacent residents. Herein, legacy polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCDs), and alternative organophosphate esters (OPEs) were investigated in indoor dust collected from three e-waste industrial parks and five adjacent villages located in south China. The levels and composition patterns varied significantly between workshop and home dust. BDE209 showed much higher (p < 0.01) concentrations in workshop dust versus home dust, while relatively comparable levels were found for OPEs and HBCDs. Principal component analysis revealed that OPEs and PBDEs were mainly related to home and workshop dust, respectively. Results strongly indicated that e-waste dismantling activities still contribute to a high burden of BDE209 to surrounding residents, whilst the sources of OPEs may also originated from household products, especially for TCEP. The estimated daily intakes (EDIs) via dust ingestion and dermal absorption for occupational worker and nearby toddlers were below available reference dose (RfD) values even at worst case scenario. This study highlights the significance of deca-BDEs rather than alternative OPEs in e-waste generated in China, which could provide scientific suggestions for policy formulation.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157307DOI Listing
July 2022

Influence of heavy metals on Saunders's Gull (Saundersilarus saundersi) reproduction in the Yellow River Estuary: risk assessment and bioaccumulation.

Environ Sci Pollut Res Int 2022 Jun 25. Epub 2022 Jun 25.

School of Life Science, Qufu Normal University, Qufu, 273165, People's Republic of China.

The heavy metal migration in the food chain exerted significant influence on the survival and reproduction of wetland birds and then disturbed and threatened the balance and health of the estuary ecosystem. In this study, the concentration of heavy metals (Cu, Cr, Fe, Mn, Cd, Ni, and Pb) in surface sediment of the Yellow River Estuary (YRE), the food sources of Saunders's Gull (Saundersilarus saundersi) nestlings, and the egg structure of birds were analyzed to determine the bioaccumulation and reproductive influence on wetland bird. The results indicated higher mean concentrations of sediment heavy metals than their corresponding background values in 2019, with the exception of Fe. Notably, the metal Cd exceeded geochemical background value by 1561.5% in 2018 and 1353.9% in 2019, resulting in severe contamination associated with Cd in the YRE (with geo-accumulation indexes of 3.44 and 3.23). Biomagnification factor (BMF) of heavy metals demonstrated that the concentrations of Cr, Ni, and Cu decreased with the trophic level rising while Cd, Mn, Pb, and Fe denoted bio-amplification in the food chain. The residual indexes showed that the food resources of Saunders's Gull were polluted by Cr, Pb, and Cu. Additionally, a higher enrichment of heavy metals was observed in the eggshell membrane. Metal concentrations had significant influences on the reproduction of Saunders's Gull, except for Cd, among which Ni, Pb, Cu, and Fe may have contributed to the reproductive success of birds, whereas the hatching failure of birds may be caused by Cr and Mn. It is of great importance to monitor the contamination of the wetland ecosystem and provide effective management and protection of the wildlife in the YRE.
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http://dx.doi.org/10.1007/s11356-022-21139-4DOI Listing
June 2022

The Correlation Between ABPM Parameters and Left Ventricular Hypertrophy in Pediatric Essential Hypertension.

Front Pediatr 2022 2;10:896054. Epub 2022 Jun 2.

Department of Cardiology, Children's Hospital, Capital Institute of Pediatrics, Beijing, China.

Objective: To explore the association of dipping pattern and blood pressure load with left ventricular hypertrophy (LVH) in pediatric essential hypertension.

Materials And Methods: Through an echocardiography monitor and an ambulatory blood pressure monitor of 425 children and adolescents diagnosed with essential hypertension with no treatment received, we identified 140 cases of LVH. Grouping patients according to LVH (LVH, = 140; n-LVH, = 285), we further evaluated their ambulatory blood pressure monitoring (ABPM) parameters by comparing dipping patterns between groups. A multivariable logistic regression analysis was used to determine the effect of blood pressure load on LVH.

Results: No significant difference was found in systolic or diastolic blood pressure dipping patterns between groups ( = 0.161, = 0.139). However, compared to the n-LVH group, the LVH group presented significant elevated nighttime systolic blood pressure (SBP) ( < 0.05), while nighttime DBP remained stable ( = 0.391), resulting in higher daytime and nighttime SBP loads, higher nighttime DBP load, and higher 24-h SBP load ( < 0.05). Notably, our multivariable logistic regression has shown that this trend of 24-h SBP load acts independently as a critical risk factor for LVH.

Conclusion: Collectively, we observed a correlation between BP load and LVH in pediatric hypertension. Our data demonstrated that SBP load has a more significant weight in LVH progression, and 24-h SBP load, in particular, acts as a critical early prognostic parameter for LVH in pediatric hypertension.
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http://dx.doi.org/10.3389/fped.2022.896054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201109PMC
June 2022

The Increased Tibiofemoral Rotation: A Potential Contributing Factor for Patellar Maltracking in Patients with Recurrent Patellar Dislocation.

Orthop Surg 2022 Jul 13;14(7):1469-1475. Epub 2022 Jun 13.

Sports Medicine Service, Beijing jishuitan hospital, Beijing, China.

Objective: The purpose of this study was to analyze the relationship between tibiofemoral rotation and patellar maltracking in patients with recurrent patellar dislocation.

Methods: A total of 143 consecutive knees (118 patients) with clinically diagnosed recurrent patellar dislocation from January 2018 to December 2019 were retrospectively analyzed. Patellar tilt angle and bisect offset index were recorded on axial CT to assesses the severity of patellar maltracking. Tibiofemoral rotation angle is measured by comparing the angle between the posterior femoral and tibial condylar lines on three-dimensional CT. The Pearson correlation was calculated to investigate the association between tibiofemoral rotation angle and patellar maltracking. Patients were divided into the rotation group (≥15°) and control group (<15°) based on the value of tibiofemoral rotation and a further comparison was performed. To further clarify the complicated relationship among tibial tubercle-trochlear groove (TT-TG), tibial tubercle-posterior cruciate ligament distance (TT-PCL), tibiofemoral rotation, and patellar maltracking, patients were divided into four subgroups according to the value of TT-TG and TT-PCL.

Results: The mean preoperative tibiofemoral rotation angle was 12° ± 6° (range, 0°-31°). Pearson correlation between patellar maltracking parameters (bisect offset index, patellar tilt angle) and various bony deformities found that the tibiofemoral rotation angle was moderately correlated with bisect offset index (r = 0.451, p < 0.001) and patellar tilt angle (r = 0.462, p < 0.001). Further results demonstrated that bisect offset index (152.1 vs 121.2, p < 0.001) and patellar tilt angle (41.2° vs 33.5°, p < 0.001) were significantly higher in the rotation group than that in control group. For patients with a TT-TG distance of >20 mm, the increased TT-TG distance was mainly caused by tibiofemoral rotation angle in group C (TT-TG > 20 mm, TT-PCL < 24 mm) and predominantly induced by tibial tubercle lateralization in group D (TT-TG > 20 mm, TT-PCL > 24 mm). Bisect offset index and patellar tilt angle were significantly higher in the group C than group D.

Conclusion: The increased tibiofemoral rotation angle is associated with patellar maltracking in patients with recurrent patellar dislocation. Patients with increased tibiofemoral rotation angle usually have more severe patellar maltracking.
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http://dx.doi.org/10.1111/os.13358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251321PMC
July 2022

Factors Affecting the Exercise Capacity in Pediatric Primary Hypertension.

Front Pediatr 2022 25;10:882223. Epub 2022 May 25.

Department of Cardiovascular Medicine, Children's Hospital Capital Institute of Pediatrics, Beijing, China.

Purpose: Exercise training is crucial to the early intervention of pediatric primary hypertension (PHT). However, much less is known about exercise capacity in this disease. This work investigated the exercise capacity in pediatric PHT and analyzed the factors affecting exercise capacity.

Methods: The study enrolled children with PHT at the Children's Hospital Capital Institute of Pediatrics between July 2017 and July 2020. The Bruce protocol of the treadmill exercise test (TET) was used to assess exercise capacity. Multivariate ordinal logistic regression and generalized linear models were used to analyze factors affecting exercise capacity.

Results: Of 190 patients, 146 (76.8%) were male, and the median age was 13 (11, 14). Most children accomplished TET and achieved the submaximal heart rates (189 [99.5%]). Children with lower resting diastolic blood pressure (DBP) and 24 h average diastolic blood pressure (ADBP) could achieve a TET stage of 6 or more, whereas children with higher DBP and ADBP could only achieve a TET stage of 3 ( all < 0.05). Children with lower DBP and 24 h ADBP were also associated with greater metabolic equivalents (METs; = -0.237, = -0.179, all < 0.05). The completion of TET stages was negatively associated with female (OR = 0.163), younger age (OR = 1.198), greater body mass index (BMI, OR = 0.921), and higher 24 h ADBP (OR = 0.952, all < 0.05). In addition, METs were negatively associated with female (β = -1.909), younger age (β = 0.282), greater BMI (β = -0.134), and higher 24 h ADBP (β = -0.063, all < 0.05).

Conclusions: Exercise capacity was impaired among pediatric PHT patients. Female gender, younger age, greater BMI, and higher 24 h ADBP are independently associated with the exercise capacity in pediatric PHT. These findings may help developing scientific exercise prescriptions for pediatric PHT.
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http://dx.doi.org/10.3389/fped.2022.882223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174901PMC
May 2022

SARS-CoV-2 N Protein Antagonizes Stress Granule Assembly and IFN Production by Interacting with G3BPs to Facilitate Viral Replication.

J Virol 2022 06 2;96(12):e0041222. Epub 2022 Jun 2.

Beijing Institute of Biotechnology, Beijing, China.

SARS-CoV-2 is the causative agent of the ongoing pandemic of coronavirus disease 2019 (COVID-19) and poses a significant threat to global health. N protein (NP), which is a major pathogenic protein among betacoronaviruses, binds to the viral RNA genome to allow viral genome packaging and viral particle release. Recent studies showed that NP antagonizes interferon (IFN) induction and mediates phase separation. Using live SARS-CoV-2 viruses, this study provides solid evidence showing that SARS-CoV-2 NP associates with G3BP1 and G3BP2 and . NP could efficiently suppress G3BP-mediated SG formation and potentiate viral infection by overcoming G3BP1-mediated antiviral innate immunity. G3BP1 conditional knockout mice (, -Cre) exhibit significantly higher lung viral loads after SARS-CoV-2 infection than wild-type mice. Our findings contribute to the growing body of knowledge regarding the pathogenicity of NP and provide insight into new therapeutics targeting NP. In this study, by assay and live SARS-CoV-2 virus infection, we provide solid evidence that the SARS-CoV-2 NP associates with G3BP1 and G3BP2 and . NP could efficiently suppress G3BP-mediated SG formation and potentiate viral infection by overcoming antiviral innate immunity mediated by G3BP1 in A549 cell lines and G3BP1 conditional knockout mice (-cKO) mice, which provide in-depth evidence showing the mechanism underlying NP-related SARS-CoV-2 pathogenesis through G3BPs.
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http://dx.doi.org/10.1128/jvi.00412-22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9215227PMC
June 2022

Multiple metal(loid) contamination reshaped the structure and function of soil archaeal community.

J Hazard Mater 2022 08 20;436:129186. Epub 2022 May 20.

College of Environmental Sciences and Engineering, Peking University, Key Laboratory of Water and Sediment Sciences, Ministry of Education, Beijing 100871, China. Electronic address:

Archaea are important participants in biogeochemical cycles of metal(loid)-polluted ecosystems, whereas archaeal structure and function in response to metal(loid) contamination remain poorly understood. Here, the effects of multiple metal(loid) pollution on the structure and function of archaeal communities were investigated in three zones within an abandoned sewage reservoir. We found that the high-contamination zone (Zone I) had higher archaeal diversity but a lower habitat niche breadth, relative to the mid-contamination zone (Zone II) and low-contamination zone (Zone III). Particularly, metal-resistant species represented by potential methanogens were markedly enriched in Zone I (cumulative relative abundance: 32.24%) compared to Zone II (1.93%) and Zone III (0.10%), and closer inter-taxon connections and higher network complexity (based on node number, edge number, and degree) were also observed compared to other zones. Meanwhile, the higher abundances of potential metal-resistant and methanogenic functions in Zone I (0.24% and 9.24%, respectively) than in Zone II (0.08% and 7.52%) and Zone III (0.01% and 1.03%) suggested archaeal functional adaptation to complex metal(loid) contamination. More importantly, six bioavailable metal(loid)s (titanium, tin, nickel, chromium, cobalt, and zinc) were the main contributors to archaeal community variations, and metal(loid) pollution reinforced the role of deterministic processes, particularly homogeneous selection, in the archaeal community assembly. Overall, this study provides the first integrated insight into the survival strategies of archaeal communities under multiple metal(loid) contamination, which will be of significant guidance for future bioremediation and environmental governance of metal(loid)-contaminated environments.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129186DOI Listing
August 2022

[Clinical efficacy and safety evaluation of acupuncture combined with moxibustion in treatment of allergic rhinitis].

Zhen Ci Yan Jiu 2022 Apr;47(4):336-42

The Third Clinical College, Shanxi University of Chinese Medicine, Taiyuan 030024.

Objective: To evaluate the clinical efficacy and safety of acupuncture combined with moxibustion on allergic rhinitis.

Methods: Using the random number table, 80 patients with allergic rhinitis were divided into a medication group and an acupuncture combined with moxibustion (acu-mox) group, 40 cases in each one. In the medication group, ioratadine tables were prescribed for oral administration, one tablet daily for 10 days as 1 session , 3 sessions of treatment were required. In the acupuncture combined with moxibustion group, bilateral Yingxiang (LI20), Yintang (EX-HN3), bilateral Hegu (LI4) and bilateral Shenshu (BL23) were selected as the main points and stimulated with acupuncture and moxibustion; and the acupoint prescription was modified according to symptoms. This combined treatment was given once every day, stimulating for 30 min each time, and 10 treatments made 1 course, for 3 courses of treatment totally. Before and after treatment, the scores for symptoms and physical signs, as well as the score of rhino-conjunctivitis related quality of life scale (R-QOL) were evaluated separately. The sample of the inferior turbinate mucosa tissue was collected and the distribution of eosinophil (EOS) was scored using HE staining and Sheldeny evaluation. Using enzyme-linked immunosorbent assay (ELISA), the contents of serum immunoglobulin E (IgE), retinoic-acid-receptor-related orphan nuclear receptor γt (RORγt), forkhead box protein P3 (Foxp3), interleukin-17 (IL-17), IL-27 and IL-33 were determined. The clinical efficacy was evaluated in the patients with allergic rhinitis of two groups and all the adverse reactions were recorded during treatment.

Results: The scores of symptoms and physical signs as well as the score of R-QOL, and EOS distribution score and the contents of serum IgE, RORγt, IL-17 and IL-33 were all reduced as compared with those before treatment in each group (<0.05), and the contents of serum Foxp3 and IL-27 were increased as compared with those before treatment in each group (<0.05). After treatment, the scores of symptoms and physical signs as well as the score of R-QOL, and the contents of serum IgE, RORγt and IL-33 in the acu-mox group were lower than those in the medication group (<0.05), and the contents of serum Foxp3 and IL-27 were higher than those of the medication group (<0.05). The total effective rate of the acu-mox group was 100.0% (40/40), significantly higher than 82.5% (33/40) in the medication group (<0.05). No ob-vious adverse reaction was found in either group during and after treatment.

Conclusion: Acupuncture combined with moxibustion is significantly effective and safe in treatment of allergic rhinitis. Its effect mechanism may be related to the balance modulation of Th1/Th2 and Th17/Treg cells mediated by naive CD4T cells.
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http://dx.doi.org/10.13702/j.1000-0607.20210315DOI Listing
April 2022

Ebola virus VP35 hijacks the PKA-CREB1 pathway for replication and pathogenesis by AKIP1 association.

Nat Commun 2022 04 26;13(1):2256. Epub 2022 Apr 26.

Beijing Institute of Biotechnology, Beijing, 100039, China.

Ebola virus (EBOV), one of the deadliest viruses, is the cause of fatal Ebola virus disease (EVD). The underlying mechanism of viral replication and EBOV-related hemorrhage is not fully understood. Here, we show that EBOV VP35, a cofactor of viral RNA-dependent RNA polymerase, binds human A kinase interacting protein (AKIP1), which consequently activates protein kinase A (PKA) and the PKA-downstream transcription factor CREB1. During EBOV infection, CREB1 is recruited into EBOV ribonucleoprotein complexes in viral inclusion bodies (VIBs) and employed for viral replication. AKIP1 depletion or PKA-CREB1 inhibition dramatically impairs EBOV replication. Meanwhile, the transcription of several coagulation-related genes, including THBD and SERPINB2, is substantially upregulated by VP35-dependent CREB1 activation, which may contribute to EBOV-related hemorrhage. The finding that EBOV VP35 hijacks the host PKA-CREB1 signal axis for viral replication and pathogenesis provides novel potential therapeutic approaches against EVD.
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http://dx.doi.org/10.1038/s41467-022-29948-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9042921PMC
April 2022

SR-CycleGAN: super-resolution of clinical CT to micro-CT level with multi-modality super-resolution loss.

J Med Imaging (Bellingham) 2022 Mar 5;9(2):024003. Epub 2022 Apr 5.

Nagoya University, Graduate School of Informatics, Furo-cho, Chikusa-ku, Nagoya, Japan.

We propose a super-resolution (SR) method, named SR-CycleGAN, for SR of clinical computed tomography (CT) images to the micro-focus x-ray CT CT ( ) level. Due to the resolution limitations of clinical CT (about ), it is challenging to obtain enough pathological information. On the other hand, scanning allows the imaging of lung specimens with significantly higher resolution (about or higher), which allows us to obtain and analyze detailed anatomical information. As a way to obtain detailed information such as cancer invasion and bronchioles from preoperative clinical CT images of lung cancer patients, the SR of clinical CT images to the level is desired. Typical SR methods require aligned pairs of low-resolution (LR) and high-resolution images for training, but it is infeasible to obtain precisely aligned paired clinical CT and images. To solve this problem, we propose an unpaired SR approach that can perform SR on clinical CT to the level. We modify a conventional image-to-image translation network named CycleGAN to an inter-modality translation network named SR-CycleGAN. The modifications consist of three parts: (1) an innovative loss function named multi-modality super-resolution loss, (2) optimized SR network structures for enlarging the input LR image to -times by width and height to obtain the SR output, and (3) sub-pixel shuffling layers for reducing computing time. Experimental results demonstrated that our method successfully performed SR of lung clinical CT images. SSIM and PSNR scores of our method were 0.54 and 17.71, higher than the conventional CycleGAN's scores of 0.05 and 13.64, respectively. The proposed SR-CycleGAN is usable for the SR of a lung clinical CT into scale, while conventional CycleGAN output images with low qualitative and quantitative values. More lung micro-anatomy information could be observed to aid diagnosis, such as the shape of bronchioles walls.
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http://dx.doi.org/10.1117/1.JMI.9.2.024003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983071PMC
March 2022

Anti-apoptotic HAX-1 suppresses cell apoptosis by promoting c-Abl kinase-involved ROS clearance.

Cell Death Dis 2022 Apr 4;13(4):298. Epub 2022 Apr 4.

Beijing Institute of Biotechnology, 27 Taiping Rd, Haidian District, 100850, Beijing, China.

The anti-apoptotic protein HAX-1 has been proposed to modulate mitochondrial membrane potential, calcium signaling and actin remodeling. HAX-1 mutation or deficiency results in severe congenital neutropenia (SCN), loss of lymphocytes and neurological impairments by largely unknown mechanisms. Here, we demonstrate that the activation of c-Abl kinase in response to oxidative or genotoxic stress is dependent on HAX-1 association. Cellular reactive oxygen species (ROS) accumulation is inhibited by HAX-1-dependent c-Abl activation, which greatly contributes to the antiapoptotic role of HAX-1 in stress. HAX-1 (Q190X), a loss-of-function mutant responsible for SCN, fails to bind with and activate c-Abl, leading to dysregulated cellular ROS levels, damaged mitochondrial membrane potential and eventually apoptosis. The extensive apoptosis of lymphocytes and neurons in Hax-1-deficient mice could also be remarkably suppressed by c-Abl activation. These findings underline the important roles of ROS clearance in HAX-1-mediated anti-apoptosis by c-Abl kinase activation, providing new insight into the pathology and treatment of HAX-1-related hereditary disease or tumorigenesis.
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http://dx.doi.org/10.1038/s41419-022-04748-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8979985PMC
April 2022

Influences of and on the Growth and Fusarium Wilt Disease Resistance of Banana.

Biology (Basel) 2022 Mar 2;11(3). Epub 2022 Mar 2.

Institute of Fruit Tree Research, Guangdong Academy of Agricultural Sciences/Key Laboratory of South Subtropical Fruit Biology and Genetic Resource Utilization (Ministry of Agriculture and Rural Affairs)/Guangdong Province Key Laboratory of Tropical and Subtropical Fruit Tree Research, Guangzhou 510640, China.

Recently, many control methods have been tried and applied in the Fusarium wilt disease control of banana and have achieved definite progresses. In this study, by using 'Zhongjiao No.3' and 'Zhongjiao No.4' banana seedlings as materials, the effects of and bamboo fungus () culture substrates on the growth and Fusarium wilt disease resistance of banana were investigated. Results showed that the plant height, leaf length, leaf width, root length and root thickness, aboveground part fresh weight, root fresh weight, and relative chlorophyll content and nitrogen content in leaves of banana seedlings colonized with were all greater than those of non-colonized controls, while these parameters of banana seedlings grown in nutrient soil containing culture substrates were significantly suppressed. Both non-colonized and colonized seedlings cultivated in nutrient containing 1/4 culture substrates showed much milder symptoms compared with those cultivated in normal nutrient soil, indicating that the addition of bamboo fungus substrates to the soil can enhance the Fusarium wilt resistance of banana. The results obtained in this study can provide a basis for the application of and bamboo fungus in the prevention and control of banana Fusarium wilt disease.
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http://dx.doi.org/10.3390/biology11030393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945148PMC
March 2022

c-Abl kinase-mediated phosphorylation of γ-tubulin promotes γ-tubulin ring complexes assembly and microtubule nucleation.

J Biol Chem 2022 04 26;298(4):101778. Epub 2022 Feb 26.

Department of Genetic Engineering, Beijing Institute of Biotechnology, Beijing, China. Electronic address:

Cytoskeletal microtubules (MTs) are nucleated from γ-tubulin ring complexes (γTuRCs) located at MT organizing centers (MTOCs), such as the centrosome. However, the exact regulatory mechanism of γTuRC assembly is not fully understood. Here, we showed that the nonreceptor tyrosine kinase c-Abl was associated with and phosphorylated γ-tubulin, the essential component of the γTuRC, mainly on the Y443 residue by in vivo (immunofluorescence and immunoprecipitation) or in vitro (surface plasmon resonance) detection. We further demonstrated that phosphorylation deficiency significantly impaired γTuRC assembly, centrosome construction, and MT nucleation. c-Abl/Arg deletion and γ-tubulin Y443F mutation resulted in an abnormal morphology and compromised spindle function during mitosis, eventually causing uneven chromosome segregation. Our findings reveal that γTuRC assembly and nucleation function are regulated by Abl kinase-mediated γ-tubulin phosphorylation, revealing a fundamental mechanism that contributes to the maintenance of MT function.
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http://dx.doi.org/10.1016/j.jbc.2022.101778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980629PMC
April 2022

Application and Development of Modern 3D Printing Technology in the Field of Orthopedics.

Biomed Res Int 2022 15;2022:8759060. Epub 2022 Feb 15.

Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, 250012 Shandong, China.

3D printing, also known as additive manufacturing, is a technology that uses a variety of adhesive materials such as powdered metal or plastic to construct objects based on digital models. Recently, 3D printing technology has been combined with digital medicine, materials science, cytology, and other multidisciplinary fields, especially in the field of orthopedic built-in objects. The development of advanced 3D printing materials continues to meet the needs of clinical precision medicine and customize the most suitable prosthesis for everyone to improve service life and satisfaction. This article introduces the development of 3D printing technology and different types of materials. We also discuss the shortcomings of 3D printing technology and the current challenges, including the poor bionics of 3D printing products, lack of ideal bioinks, product safety, and lack of market supervision. We also prospect the future development trends of 3D printing.
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http://dx.doi.org/10.1155/2022/8759060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8863440PMC
March 2022

Limited Recognition of Highly Conserved Regions of SARS-CoV-2.

Microbiol Spectr 2022 02 23;10(1):e0278021. Epub 2022 Feb 23.

QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institutegrid.1049.c, Brisbane, Queensland, Australia.

Understanding the immune response to severe acute respiratory syndrome coronavirus (SARS-CoV-2) is critical to overcome the current coronavirus disease (COVID-19) pandemic. Efforts are being made to understand the potential cross-protective immunity of memory T cells, induced by prior encounters with seasonal coronaviruses, in providing protection against severe COVID-19. In this study we assessed T-cell responses directed against highly conserved regions of SARS-CoV-2. Epitope mapping revealed 16 CD8 T-cell epitopes across the nucleocapsid (N), spike (S), and open reading frame (ORF)3a proteins of SARS-CoV-2 and five CD8 T-cell epitopes encoded within the highly conserved regions of the ORF1ab polyprotein of SARS-CoV-2. Comparative sequence analysis showed high conservation of SARS-CoV-2 ORF1ab T-cell epitopes in seasonal coronaviruses. Paradoxically, the immune responses directed against the conserved ORF1ab epitopes were infrequent and subdominant in both convalescent and unexposed participants. This subdominant immune response was consistent with a low abundance of ORF1ab encoded proteins in SARS-CoV-2 infected cells. Overall, these observations suggest that while cross-reactive CD8 T cells likely exist in unexposed individuals, they are not common and therefore are unlikely to play a significant role in providing broad preexisting immunity in the community. T cells play a critical role in protection against SARS-CoV-2. Despite being highly topical, the protective role of preexisting memory CD8 T cells, induced by prior exposure to circulating common coronavirus strains, remains less clear. In this study, we established a robust approach to specifically assess T cell responses to highly conserved regions within SARS-CoV-2. Consistent with recent observations we demonstrate that recognition of these highly conserved regions is associated with an increased likelihood of milder disease. However, extending these observations we observed that recognition of these conserved regions is rare in both exposed and unexposed volunteers, which we believe is associated with the low abundance of these proteins in SARS-CoV-2 infected cells. These observations have important implications for the likely role preexisting immunity plays in controlling severe disease, further emphasizing the importance of vaccination to generate the immunodominant T cells required for immune protection.
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http://dx.doi.org/10.1128/spectrum.02780-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8865427PMC
February 2022

Coupling electrode aeration and hydroxylamine for the enhanced Electro-Fenton degradation of organic contaminant: Improving HO generation, Fe/Fe cycle and N selectivity.

Water Res 2022 Feb 8;214:118167. Epub 2022 Feb 8.

State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin 150090, China. Electronic address:

To improve HO generation and Fe/Fe cycle simultaneously for enhancing Electro-Fenton performance, the electrode aeration (EA) and hydroxylamine sulfate (HA) were coupled. With dimethyl phthalate (DMP) as main target contaminant, combination of HA and EA greatly accelerated the degradation of DMP and exhibited a synergy in the pH of 2.0-6.9 through promoting the key reactions, including electrochemical two-electron reduction of O into HO and redox cycles of Fe/Fe, which then improved the generation of hydroxyl radicals (·OH). The coupling EA and HA reduced the use of HA and converted most of HA into environment-friendly N (60.1-62.1% of HA products), while HA/solution aeration(SA) system consumed HA rapidly and the generated N only accounted for 5.8-6.7% of HA products. Furthermore, compared with HA/SA and EA Electro-Fenton systems, enhancement degree of DMP degradation in HA/EA Electro-Fenton process was higher in actual waterbody than in ultrapure water. The coupling EA and HA in the Electro-Fenton process could solve the low Fe/Fe cycle efficiency and low HO production simultaneously, and improve the N selectivity of HA transformation, which advanced its application in practical environmental remediation.
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http://dx.doi.org/10.1016/j.watres.2022.118167DOI Listing
February 2022

Genome-wide identification of FAD gene family and their contributions to the temperature stresses and mutualistic and parasitic fungi colonization responses in banana.

Int J Biol Macromol 2022 Apr 15;204:661-676. Epub 2022 Feb 15.

College of Horticulture, Fujian Agriculture and Forestry University, Fuzhou 350002, China. Electronic address:

Fatty acid desaturase (FAD) plays important roles in plant growth and development and plant defense processes. In this study, we identified 27 MaFAD genes from the banana genome. According to the amino acid sequence similarities, their encoded proteins could be classified into five subfamilies. This classification is consistently supported by their gene and protein structures, conserved motifs and subcellular localizations. Segmental duplication events were found to play predominant roles in the MaFAD gene family expansion. Thirty miRNAs targeting MaFADs were identified and many hormone- and stress-responsive cis-acting elements and transcription factor binding sites (TFBSs) were identified in their promoters, indicating that the MaFADs expression regulation was very complicated. Gene expression analysis showed that some MaFADs showed significant differential expression in response to high and low temperature. FocTR4 influenced greatly the expression of several MaFADs and greatly induced the fatty acid (FA) accumulations in roots. Although S. indica showed no significant influence on the expression of most MaFADs, it could greatly alleviate the influence of FocTR4 on several MaFADs and FA biosynthesis. Our study revealed that MaFADs contributed greatly to the responses of high and low temperature stresses and mutualistic and parasitic fungi colonization in banana.
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http://dx.doi.org/10.1016/j.ijbiomac.2022.02.024DOI Listing
April 2022

Biological enhancement methods may be a viable option for ACL arthroscopic primary repair - A systematic review.

Orthop Traumatol Surg Res 2022 05 2;108(3):103227. Epub 2022 Feb 2.

Department of Sports Medicine, Beijing Jishuitan Hospital, No. 31, Xinjiekou East Street, 10035 Beijing, China. Electronic address:

Background: Bioactive factors combined with advanced anterior cruciate ligament (ACL) primary repair technology have been used to treat ACL repairs. The current review was conducted to identify whether biological enhancement could enable superior clinical outcome, including side-to-side difference, failure rate, reoperation rate and subjective scores.

Hypothesis: The implementation of ACL primary repair with biological enhancement will provide better clinical outcomes in terms of side-to-side differences, failure rate, reoperation rate and subjective scores than ACL primary repair alone.

Materials And Methods: A systematic literature review was performed following PRISMA guidelines by searching all studies reporting outcomes of arthroscopic primary repair with or without biological augmentation published until April 19, 2020, in Medline, PubMed, Embase and the Cochrane Library. Primary metrics were side-to-side differences, failure rate and reoperation rate, as well as measurements of patient-reported outcomes at the last follow-up.

Results: A total of 20 studies were finally included in this work, of which 3 were Grade I (15%), 3 studies were Grade III (15%), and 14 studies were Grade IV (70%) in terms of the level of evidence. There were 729 patients with a mean age of 30 (range: 8-68) years, and the mean follow-up period of which was 38 (range: 3-122) months. At the final follow-up, the postoperative side-to-side differences (the proportion of patients with a side-to-side difference less than 3mm) and patient-report outcomes were significantly better in the biological enhancement group. Nevertheless, there were no significant differences between the two groups in the rate of surgical failure, the rate of revision, or the positive Lachman test or pivot shift test.

Conclusion: Biologically enhanced arthroscopic ACL primary repair was superior to ACL primary repair alone in terms of postoperative side-to-side differences (proportion of patients with a side-to-side difference less than 3mm) and patient-reported outcomes. Thus, biologically enhanced arthroscopic ACL primary repair can be preferentially recommended over ACL arthroscopic primary repair alone.

Level Of Evidence: IV, systematic review.
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http://dx.doi.org/10.1016/j.otsr.2022.103227DOI Listing
May 2022

Redox Metabolism-Associated Molecular Classification of Clear Cell Renal Cell Carcinoma.

Oxid Med Cell Longev 2022 21;2022:5831247. Epub 2022 Jan 21.

Department of Kidney Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma. Redox metabolism has been recognized as the hallmark of cancer. But the concrete role of redox-related genes in patient stratification of ccRCC remains unknown. Herein, we aimed to characterize the molecular features of ccRCC based on the redox gene expression profiles from The Cancer Genome Atlas. Differentially expressed redox genes (DERGs) and vital genes in metabolism regulation were identified and analyzed in the ccRCC. Consensus clustering was performed to divide patients into three clusters (C1, C2, and C3) based on 139 redox genes with median FPKM value > 1. We analyzed the correlation of clusters with clinicopathological characteristics, immune infiltration, gene mutation, and response to immunotherapy. Subclass C1 was metabolic active with moderate prognosis and associated with glucose, lipid, and protein metabolism. C2 had intermediate metabolic activity with worse prognosis and correlated with more tumor mutation burden, neoantigen, and aneuploidy, indicating possible drug sensitivities towards immune checkpoint inhibitors. Metabolic exhausted subtype C3 showed high cytolytic activity score, suggesting better prognosis than C1 and C2. Moreover, the qRT-PCR was performed to verify the expression of downregulated DERGs including ALDH6A1, ALDH1L1, GLRX5, ALDH1A3, and GSTM3, and upregulated SHMT1 in ccRCC. Overall, our study provides an insight into the characteristics of molecular classification of ccRCC patients based on redox genes, thereby deepening the understanding of heterogeneity of ccRCC and allowing prediction of prognosis of ccRCC patients.
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http://dx.doi.org/10.1155/2022/5831247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8799361PMC
March 2022

MVS-GCN: A prior brain structure learning-guided multi-view graph convolution network for autism spectrum disorder diagnosis.

Comput Biol Med 2022 03 19;142:105239. Epub 2022 Jan 19.

Amii, University of Alberta, Edmonton, Alberta, Canada.

Purpose: Recently, functional brain networks (FBN) have been used for the classification of neurological disorders, such as Autism Spectrum Disorders (ASD). Neurological disorder diagnosis with FBN is a challenging task due to the high heterogeneity in subjects and the noise correlations in brain networks. Meanwhile, it is challenging for the existing deep learning models to provide interpretable insights into the brain network. We propose a machine learning approach for the classification of neurological disorders while providing an interpretable framework.

Method: In this paper, we build upon graph neural network in order to learn effective representations for brain networks in an end-to-end fashion. Specifically, we present a prior brain structure learning-guided multi-view graph convolutional neural network (MVS-GCN), which collaborates the graph structure learning and multi-task graph embedding learning to improve the classification performance and identify the potential functional subnetworks.

Results: To demonstrate the effectiveness of our approach, we evaluate the performance of the proposed method on the Autism Brain Imaging Data Exchange (ABIDE) dataset and Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. The experimental results indicate that our MVS-GCN can achieve enhanced performance compared with state-of-the-art methods. Notably, MVS-GCN achieves an average accuracy/AUC of 69.38%/69.01% on the ABIDE dataset. Moreover, the obtained results from our model show high consistency with the previous neuroimaging derived evidence of within and between-networks biomarkers for ASD. The discovered subnetworks are used as evidence for the proposed MVS-GCN model.

Conclusion: The proposed MVS-GCN method performs a graph embedding learning from the multi-views graph embedding learning perspective while considering eliminating the heterogeneity in brain networks and enhancing the feature representation of functional subnetworks, which can capture the essential embeddings to improve the classification performance of brain disorder diagnosis. The code is available at https://github.com/GuangqiWen/MVS-GCN.
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http://dx.doi.org/10.1016/j.compbiomed.2022.105239DOI Listing
March 2022

Unveil the role of dissolved and sedimentary metal(loid)s on bacterial communities and metal resistance genes (MRGs) in an urban river of the Qinghai-Tibet Plateau.

Water Res 2022 Mar 8;211:118050. Epub 2022 Jan 8.

College of Environmental Sciences and Engineering, Key Laboratory of Water and Sediment Sciences, Ministry of Education, Peking University, Beijing 100871, China; State Environmental Protection Key Laboratory of All Materials Fluxes in River Ecosystems, Beijing 100871, China.

Though metal resistance genes (MRGs) are of global concern in aquatic ecosystems, the underlying factors responsible for MRGs dissemination, especially in urban rivers on the vulnerable Qinghai-Tibet Plateau, are rarely known. Here, we collected 64 samples including water and sediments during the wet and dry seasons and effluents from six wastewater treatment plants (WWTPs) during the dry season and measured 50 metal(loid)s, 60 bacterial phyla, and 259 MRGs. We observed the distinct difference of metal(loid)s, bacterial communities, and MRGs between water and sediments and the great seasonal changes in metal(loid)s and bacterial communities instead of MRGs. Thirty-one metal(loid)s were detectable in the water, with relatively low concentrations and no significant effects on the planktonic bacterial communities and MRGs. Interestingly, the WWTPs effluent partially promoted the prevalence of dissolved metal(loid)s, bacterial communities, and MRGs along the river. In the sediments, the average concentrations of 17 metal(loid)s exceeded their corresponding background levels in this region and strongly influenced the bacterial communities and the MRGs. Sedimentary Hg and Cd, mainly sourced from the intensive animal husbandry, were the major pollutants causing ecological risks and largely shaped their corresponding resistomes. Moreover, we found that bacterial communities predominantly determined the variation of MRGs in both water and sediments. Metagenome-assembled genomes further reveals the widespread co-occurrence of MRGs and antibiotic resistance genes (ARGs) in MRG hosts. Our study highlighted the concern of effluents discharged from WWTPs and emphasized the importance of controlling the anthropogenic inputs of sedimentary metal(loid)s in the plateau river ecosystems.
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http://dx.doi.org/10.1016/j.watres.2022.118050DOI Listing
March 2022

Derotational Femoral Osteotomy for Treating Recurrent Patellar Dislocation in the Presence of Increased Femoral Anteversion: A Systematic Review.

Orthop J Sports Med 2021 Nov 22;9(11):23259671211057126. Epub 2021 Nov 22.

Sports Medicine Service, Beijing Jishuitan Hospital, Beijing, China.

Background: Studies on the clinical outcomes of derotational femoral osteotomy to treat recurrent patellar dislocation in the presence of increased femoral anteversion are limited.

Purpose: To investigate the role of derotational femoral osteotomy in the treatment of recurrent patellar dislocation in the presence of increased femoral anteversion.

Study Design: Systematic review; Level of evidence, 4.

Methods: A systematic review was performed according to the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-analyses) by searching the Medline, Embase, Web of Science, and Cochrane Library databases through February 10, 2021. Included were studies of skeletally mature patients presenting with recurrent patellar dislocation and exhibiting increased femoral anteversion who subsequently underwent derotational femoral osteotomy. Methodological quality was assessed using the MINORS (Methodological Index for Nonrandomized Studies) score. The basic characteristics of each study were recorded and analyzed: characteristic information, radiological parameters, surgical techniques, patient-reported outcomes, and complications.

Results: A total of 6 studies with 163 patients (170 knees) were included. Sample sizes ranged from 7 to 66 patients, and the patients were predominantly women (range, 79%-100%). The mean age and follow-up ranges were 18 to 28 years and 16 to 44 months, respectively. The mean femoral anteversion decreased significantly from 34° preoperatively to 12° postoperatively. In studies reporting pre- and postoperative outcomes, significant improvements were found in the Lysholm score (from 24.8 to 44.1), Kujala score (from 15.8 to 41.9), International Knee Documentation Committee score (from 11.0 to 28.0), and visual analog scale for pain (from 2.0 to 3.7). All studies reported postoperative complications, giving an overall reported complication rate of 4.7%, but no redislocations occurred during the follow-up period.

Conclusion: For recurrent patellar dislocation in the presence of increased femoral anteversion, combination treatment with derotational femoral osteotomy led to favorable clinical outcomes with a low redislocation rate. However, there was no consensus among researchers on the indications for derotational femoral osteotomy in the treatment of recurrent patellar dislocation.
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http://dx.doi.org/10.1177/23259671211057126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8647269PMC
November 2021

Derotational distal femoral osteotomy yields satisfactory clinical outcomes in pathological femoral rotation with failed medial patellofemoral ligament reconstruction.

Knee Surg Sports Traumatol Arthrosc 2022 May 1;30(5):1809-1817. Epub 2021 Oct 1.

Department of Sports Medicine, Sports Medicine Service, Beijing Jishuitan Hospital, No. 31, Xinjiekou East Street, Beijing, 10035, China.

Purpose: The purpose of this study was to evaluate the clinical outcomes of de-rotational distal femoral osteotomy (DDFO) in patients who underwent primary medial patellofemoral ligament reconstruction (MPFLR) failure with increased femoral anteversion along with high-grade J sign.

Methods: Between 2011 and 2019, 14 patients underwent DDFO revision surgery due to failed MPFLR. The pre- and postoperative J sign grade, Caton-Deschamps index (CDI), tibial tuberosity-trochlear groove (TT-TG) distance, femoral anteversion angle (FAA), patellar lateral tilt angle (PLTA), MPFL graft laxity, and patient-reported outcomes (Kujala, Lysholm, Tegner, and International Knee Documentation Committee (IKDC) subjective scores) were collected. The anterior-posterior and proximal-distal distances between the actual point and the Schöttle point were also calculated.

Results: Fourteen patients underwent MPFLR revision by DDFO combined with MPFLR. The mean PLTA improved from 40.7° ± 11.9° to 20.5° ± 8.7° (P < 0.001). The mean FAA significantly decreased from 42.7° ± 12.0° to 14.1° ± 5.2° (P < 0.001). The mean patellar laxity index (PLI) decreased from 82.4% preoperatively to 15.1% postoperatively (P < 0.001). None of these patients experienced subluxation or re-dislocation during follow-up of 29.7 ± 5.0 months after revision surgery. Meanwhile, the Tegner score at the last follow-up ranged from 3 to 6, with a median of 5. The Kujala, Lysholm, and IKDC subjective scores showed significant improvements, from a mean of 51.0 ± 6.8 preoperatively to 75.4 ± 5.1 postoperatively (P < 0.001), 49.2 ± 7.9 to 75.2 ± 7.2 (P < 0.001), and 42.9 ± 6.2 to 76.8 ± 6.0 (P < 0.001), respectively. The proportion of patients with a high-grade J sign was significantly lower postoperatively than preoperatively (100% vs. 14%). Four out of 14 patients (29%) showed femoral tunnel mal-positioning.

Conclusion: MPFLR revision by DDFO combined with MPFLR achieved favorable clinical outcomes in patients with increased femoral anteversion along with high-grade J sign.

Level Of Evidence: IV.
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http://dx.doi.org/10.1007/s00167-021-06739-wDOI Listing
May 2022

Neonatal Transplant in Hypoxic Injury.

Methods Mol Biol 2022 ;2389:155-164

Department of Pediatrics, University of Florida, Gainesville, FL, USA.

Even with therapeutic hypothermia as standard of care, hypoxic-ischemic encephalopathy in neonates often causes long-term disabilities. Stem cell therapy may be a successful treatment for HIE both in the acute and chronic time periods post-injury. Neurogenic astrocytes with characteristics of neural stem cells can be cultured as adherent monolayers and be induced to generate neuronal progeny in vitro and in vivo following reintroduction into the neural stem cell niche of both neonatal and adult hosts. Thus, these neurogenic astrocytes represent promising candidates for cell replacement therapy in HIE. Such an approach requires optimized cell cultivation protocols as well as extensive testing of donor cells to assess their capacity for engraftment, survival, and integration in the HIE animal models. In this chapter, we will describe methods of generating the HIE model, generating and culturing monolayer neurogenic astrocytes, and transplanting these cells into HIE animal models.
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http://dx.doi.org/10.1007/978-1-0716-1783-0_13DOI Listing
December 2021

A multiscale model of cerebral autoregulation.

Med Eng Phys 2021 09 12;95:51-63. Epub 2021 Aug 12.

Institute of Biomedical Engineering, Department of Engineering Science, Old Road Campus Research Building, University of Oxford, Headington, Oxford OX3 7DQ, UK.

The mechanism of cerebral autoregulation ensures a continuous and sufficient blood supply to the brain to maintain normal function in the presence of changes in blood pressure. Impaired cerebral autoregulation is implicated in a range of brain diseases. We thus present here a multiscale model of cerebral autoregulation to provide a more detailed basis for a better understanding of the mechanisms behind impaired autoregulation. This model is built around a model of single arteriole, which includes a model of Nitric Oxide (NO) transport, the myogenic response, and a 4-state kinetic model coupled to a mechanical model of the vessel wall. In particular, the NO component of the model is added here to better understand the interaction mode between NO and the myogenic response, since the role of NO, the recognized effective vasodilator, is poorly understood in this context. This vessel model is then integrated within a model of the full-brain vasculature. The model is validated using a range of experimental data from the literature, both steady-state and dynamic. The model is able to predict the response of the arteriole to changes in both driving pressure and baseline pressure, indicating that the model captures well the balance between the myogenic and metabolic mechanisms. We next plan to examine the ways in which impaired autoregulation is manifested in different patient groups, potentially leading to improved therapy.
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http://dx.doi.org/10.1016/j.medengphy.2021.08.003DOI Listing
September 2021

Anchored Pt-Co Nanoparticles on Honeycombed Graphene as Highly Durable Catalysts for the Oxygen Reduction Reaction.

ACS Appl Mater Interfaces 2021 Jul 13;13(29):34397-34409. Epub 2021 Jul 13.

School of Chemical Science and Engineering, Tongji University, Shanghai 200092, China.

Durability is an important factor in evaluating the performance of a catalyst. In this work, the spatial protection of the carrier to nanoparticles was considered to improve the durability of the catalyst. It is found that a honeycombed graphene with a three-dimensional (3D)-hierarchical porous structure (3D HPG) can help to reduce the shedding of Pt-Co nanoparticles (Pt-Co NPs) because 3D HPG can form a protective layer to reduce the direct erosion of Pt-Co NPs on the interface by an electrolyte. Then, appropriate oxygen groups were introduced on the 3D reduced hierarchical porous graphene oxide (3D rHPGO) to improve the dispersion of Pt-Co NPs on the surface of the carrier. It was found that the Pt d-band of the catalyst was anchored by π sites of carbonyl of an oxygen group. After optimization, the catalyst (referred to as Pt-Co/3D rHPGO) achieved a 2-fold enhancement in mass activity than that of a commercial Pt/C catalyst. More importantly, after the accelerated durability test (ADT) of 20 000 cycles, the Pt-Co/3D rHPGO catalyst can almost sustain this level of performance, whereas other catalysts showed a comparatively large loss of activity. According to the results, the high durability of Pt-Co/3D rHPGO was attributed to spatial protection of Pt-Co NPs and the defects on the surface allowed the electrolyte to enter. In addition, oxygen groups provided an anchoring effect on nanoparticles. Thus, the Pt-Co/3D rHPGO electrocatalyst exhibited splendid durability, holding a potential to be applied in PEMFC for long-term work.
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http://dx.doi.org/10.1021/acsami.1c08810DOI Listing
July 2021

Increased Posterior Tibial Slope Is Associated With Greater Risk of Graft Roof Impingement After Anatomic Anterior Cruciate Ligament Reconstruction.

Am J Sports Med 2021 07 23;49(9):2396-2405. Epub 2021 Jun 23.

Sports Medicine Service, Beijing Jishuitan Hospital, Beijing, China.

Background: Increased posterior tibial slope (PTS) has been reported to be associated with irreducible anterior tibial subluxation in extension after anatomic anterior cruciate ligament (ACL) reconstruction (ACLR), which raises concerns about the greater risk of graft roof impingement (GRI) although the tibial tunnel is positioned anatomically.

Hypothesis: Increased PTS would be associated with greater risk of GRI after anatomic ACLR.

Study Design: Case-control study; Level of evidence, 3.

Methods: Between January 2016 and December 2017, a total of 418 consecutive patients were diagnosed as having noncontact ACL injuries and underwent primary anatomic ACLR. Among them, 26 patients had ≥1 of the following features during the second-look arthroscopy: fractured/guillotined bundles at the tibial insertion or cyclops lesion. These patients were confirmed to have GRI and were allocated to the study group. They were also matched 1:2 to 52 control participants without GRI. PTS was measured on true lateral whole-leg radiographs. Intra-articular ACL graft signal intensity was evaluated on postoperative magnetic resonance imaging scans (mean, 32.8 months; range, 26-38 months) and divided into 3 grades (I, good; II, moderate; III, poor) based on degree of GRI. Moreover, anterior subluxation of the lateral compartment (ASLC) and medial compartment (ASMC) in extension relative to the femoral condyles were measured on postoperative magnetic resonance imaging scans and compared between the groups. In addition, predictors of GRI were evaluated using multivariate logistic regression analysis and included body mass index, PTS, pivot-shift test, KT-1000 side-to-side difference, and concomitant meniscal tears.

Results: PTS in the study group was significantly higher than that in control group (mean ± SD, 13.8°± 1.5° vs 9.5°± 1.8°; < .05). In the study group (n = 26), patients with grade III (poor) graft signal intensity (n = 9) showed significantly higher PTS than those with grade II (moderate; n = 17) (16.4°± 1.7° vs 12.4°± 1.3°; < .05). Moreover, the mean postoperative ASLC and ASMC in extension were significantly larger in the study group than the control group (ASLC, 4.1 ± 1.3 vs 0.8 ± 0.4 mm; ASMC, 4.3 ± 1.5 vs 0.9 ± 0.3 mm; < .05). Furthermore, the abnormal degree of PTS (≥12°) was determined to be an independent risk factor associated with GRI after anatomic ACLR (odds ratio, 9.0 [95% CI, 3.7-30.2]; < .001), whereas body mass index, grade of pivot-shift test, KT-1000 side-to-side difference, and concomitant meniscal tears were not.

Conclusion: Increased PTS (≥12°) was associated with greater risk of GRI after anatomic ACLR. This may provide additional information for counseling patients with greater risk of GRI.
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http://dx.doi.org/10.1177/03635465211018859DOI Listing
July 2021

Rapid Artificial Intelligence Solutions in a Pandemic - The COVID-19-20 Lung CT Lesion Segmentation Challenge.

Res Sq 2021 Jun 4. Epub 2021 Jun 4.

Artificial intelligence (AI) methods for the automatic detection and quantification of COVID-19 lesions in chest computed tomography (CT) might play an important role in the monitoring and management of the disease. We organized an international challenge and competition for the development and comparison of AI algorithms for this task, which we supported with public data and state-of-the-art benchmark methods. Board Certified Radiologists annotated 295 public images from two sources (A and B) for algorithms training (n=199, source A), validation (n=50, source A) and testing (n=23, source A; n=23, source B). There were 1,096 registered teams of which 225 and 98 completed the validation and testing phases, respectively. The challenge showed that AI models could be rapidly designed by diverse teams with the potential to measure disease or facilitate timely and patient-specific interventions. This paper provides an overview and the major outcomes of the COVID-19 Lung CT Lesion Segmentation Challenge - 2020.
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http://dx.doi.org/10.21203/rs.3.rs-571332/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183044PMC
June 2021
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