Publications by authors named "Lin Yu"

1,139 Publications

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A Pilot Behavioural and Neuroimaging Investigation on Photothrombotic Stroke Models in Rhesus Monkeys.

J Neurosci Methods 2021 Jul 19:109291. Epub 2021 Jul 19.

National Resource Center for Non-Human Primates, Kunming Primate Research Center, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China. Electronic address:

Background: Ischemic stroke leads to a long-term disability in humans and no efficient clinical therapy exists to date. The middle cerebral artery occlusion (MCAO) model in non-human primates has shown to be of value for translational stroke research. New method In the current study, a photothrombotic (PT) stroke model was established in rhesus monkeys with either a proximal or distal segment of middle cerebral artery (MCA) thrombosis. This study is the first that compares the two approaches of PT stroke in monkeys using behavioral and physiological measurements and MRI scans.

Results: The experiment found that infarct occurred in the MCA target regions, with all monkeys having impaired behavior reflected by deficits in neurologic function, and motor and cognition in object retrieval detour (ORD) task. The monkeys with distal MCA thrombosis developed with sequential photo-irritations of the Sylvian fissure zone, adjacent central anterior gyrus and central posterior gyrus, had similar impairments with respect to behavior and showed a tendency of a small edema volume with proximal MCA thrombosis at days 4 and 7 post PT stroke.

Comparison With Existing Methods: The distal MCA thrombosis developed with sequential photo-irritations might provide a consistent and well-tolerated focal ischemia in rhesus monkeys, compared with other PT stroke models which usually were singly conducted on the animal's motor cortex and had a temporal effect.

Conclusions: The sequentially photo-irritated PT stroke model is a promising ischemic stroke model in rhesus monkey for studying human stroke pathology and physiology and for new therapies development.
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http://dx.doi.org/10.1016/j.jneumeth.2021.109291DOI Listing
July 2021

Identification of NOTCH4 mutation as a response biomarker for immune checkpoint inhibitor therapy.

BMC Med 2021 Jul 21;19(1):154. Epub 2021 Jul 21.

Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Background: Immune checkpoint inhibitor (ICI) therapy elicits durable antitumor responses in patients with many types of cancer. Genomic mutations may be used to predict the clinical benefits of ICI therapy. NOTCH homolog-4 (NOTCH4) is frequently mutated in several cancer types, but its role in immunotherapy is still unclear. Our study is the first to study the association between NOTCH4 mutation and the response to ICI therapy.

Methods: We tested the predictive value of NOTCH4 mutation in the discovery cohort, which included non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, esophagogastric cancer, and bladder cancer patients, and validated it in the validation cohort, which included non-small cell lung cancer, melanoma, renal cell carcinoma, colorectal cancer, esophagogastric cancer, glioma, bladder cancer, head and neck cancer, cancer of unknown primary, and breast cancer patients. Then, the relationships between NOTCH4 mutation and intrinsic and extrinsic immune response mechanisms were studied with multiomics data.

Results: We collected an ICI-treated cohort (n = 662) and found that patients with NOTCH4 mutation had better clinical benefits in terms of objective response rate (ORR: 42.9% vs 25.9%, P = 0.007), durable clinical benefit (DCB: 54.0% vs 38.1%, P = 0.021), progression-free survival (PFS, hazard ratio [HR] = 0.558, P < 0.001), and overall survival (OS, HR = 0.568, P = 0.006). In addition, we validated the prognostic value of NOTCH4 mutation in an independent ICI-treated cohort (n = 1423). Based on multiomics data, we found that NOTCH4 mutation is significantly associated with enhanced immunogenicity, including a high tumor mutational burden, the expression of costimulatory molecules, and activation of the antigen-processing machinery, and NOTCH4 mutation positively correlates activated antitumor immunity, including infiltration of diverse immune cells and various immune marker sets.

Conclusions: Our findings indicated that NOTCH4 mutation serves as a novel biomarker correlated with a better response to ICI therapy.
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http://dx.doi.org/10.1186/s12916-021-02031-3DOI Listing
July 2021

Understanding three-dimensional chromatin organization in diploid genomes.

Comput Struct Biotechnol J 2021 15;19:3589-3598. Epub 2021 Jun 15.

Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.

The three-dimensional (3D) organization of chromatin in the nucleus of diploid eukaryotic organisms has fascinated biologists for many years. Despite major progress in chromatin conformation studies, current knowledge regarding the spatial organization of diploid (maternal and paternal) genomes is still limited. Recent advances in Hi-C technology and data processing approaches have enabled construction of diploid Hi-C contact maps. These maps greatly accelerated the pace of novel discoveries in haplotype-resolved 3D genome studies, revealing the role of allele biased chromatin conformation in transcriptional regulation. Here, we review emerging concepts and haplotype phasing strategies of Hi-C data in 3D diploid genome studies. We discuss new insights on homologous chromosomal organization and the interplay between allelic biased chromatin architecture and several nuclear functions, explaining how haplotype-resolved Hi-C technologies have been used to resolve important biological questions.
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http://dx.doi.org/10.1016/j.csbj.2021.06.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246089PMC
June 2021

Research on enterprise business model and technology innovation based on artificial intelligence.

EURASIP J Wirel Commun Netw 2021 3;2021(1):145. Epub 2021 Jul 3.

College of Management, Wuxi Institute of Technology, Wuxi, 214121 China.

Small- and medium-sized enterprises (SEMs) are the important part of economic society whose innovation activities are of great significance for building innovative country. In order to investigate how technological innovation (TI) and business model design (BMD) affect the business performance of SMEs, samples of 268 SMEs in the artificial intelligence industry and hierarchical regression models are used in the analysis. The results indicate that TI, BMD, and the matching of them have different effects on the innovation of SMEs of different sizes. These findings are helpful for enriching the theory of the fit between TI and BMD and providing theoretical guidance for the innovation activities in SEMs.
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http://dx.doi.org/10.1186/s13638-021-02025-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254430PMC
July 2021

Biomechanical cues as master regulators of hematopoietic stem cell fate.

Cell Mol Life Sci 2021 Jul 7. Epub 2021 Jul 7.

Bone Marrow Transplantation Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310012, Zhejiang, People's Republic of China.

Hematopoietic stem cells (HSCs) perceive both soluble signals and biomechanical inputs from their microenvironment and cells themselves. Emerging as critical regulators of the blood program, biomechanical cues such as extracellular matrix stiffness, fluid mechanical stress, confined adhesiveness, and cell-intrinsic forces modulate multiple capacities of HSCs through mechanotransduction. In recent years, research has furthered the scientific community's perception of mechano-based signaling networks in the regulation of several cellular processes. However, the underlying molecular details of the biomechanical regulatory paradigm in HSCs remain poorly elucidated and researchers are still lacking in the ability to produce bona fide HSCs ex vivo for clinical use. This review presents an overview of the mechanical control of both embryonic and adult HSCs, discusses some recent insights into the mechanisms of mechanosensing and mechanotransduction, and highlights the application of mechanical cues aiming at HSC expansion or differentiation.
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http://dx.doi.org/10.1007/s00018-021-03882-yDOI Listing
July 2021

A MicroRNA Exerts Antitumor Effects Through Inhibition of Both Cell Migration and Angiogenesis by Targeting PGAM1.

Front Oncol 2021 16;11:652395. Epub 2021 Jun 16.

Institute for Infectious Diseases and Vaccine Development, Tongji University School of Medicine, Shanghai, China.

MicroRNA (miRNA) is an important regulator for gene expression. Recent studies showed that some heterogenous miRNAs derived from both parasite and plant can regulate expression of mammalian gene in a cross-species or even a cross-kingdom manner. Here, we identified a miRNA (designated as sja-miR-61) that is present in the hepatocyte of mice infected with the parasite. The sja-miR-61 mimics significantly inhibited the migration of both mouse and human hepatoma cells . In a xenograft animal model, significant reductions of the tumor volume and weight were observed in mice inoculated with hepatoma cells transfected with sja-miR-61 mimics compared to the controls. We found that the inhibition of tumor growth was through its anti-angiogenesis activity. Mechanically, we identified the phosphoglycerate mutase 1 () gene as a target of sja-miR-61 and found that the sja-miR-61-mediated suppression of cell migration and anti-angiogenesis by cross-species down-regulation of PGAM1 expression. These data indicated that sja-miR-61 is a tumor suppressor miRNA that may have therapeutic potential for human cancers.
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http://dx.doi.org/10.3389/fonc.2021.652395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242254PMC
June 2021

Prediction of skin disease using a new cytological taxonomy based on cytology and pathology with deep residual learning method.

Sci Rep 2021 Jul 2;11(1):13764. Epub 2021 Jul 2.

Sino-French Hoffmann Institute, School of Basic Sciences, The Second Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Guangzhou Medical University, Guangzhou, 511436, Guangdong, China.

With the development of artificial intelligence, technique improvement of the classification of skin disease is addressed. However, few study concerned on the current classification system of International Classification of Diseases, Tenth Revision (ICD)-10 on Diseases of the skin and subcutaneous tissue, which is now globally used for classification of skin disease. This study was aimed to develop a new taxonomy of skin disease based on cytology and pathology, and test its predictive effect on skin disease compared to ICD-10. A new taxonomy (Taxonomy 2) containing 6 levels (Project 2-4) was developed based on skin cytology and pathology, and represents individual diseases arranged in a tree structure with three root nodes representing: (1) Keratinogenic diseases, (2) Melanogenic diseases, and (3) Diseases related to non-keratinocytes and non-melanocytes. The predictive effects of the new taxonomy including accuracy, precision, recall, F1, and Kappa were compared with those of ICD-10 on Diseases of the skin and subcutaneous tissue (Taxonomy 1, Project 1) by Deep Residual Learning method. For each project, 2/3 of the images were included as training group, and the rest 1/3 of the images acted as test group according to the category (class) as the stratification variable. Both train and test groups in the Projects (2 and 3) from Taxonomy 2 had higher F1 and Kappa scores without statistical significance on the prediction of skin disease than the corresponding groups in the Project 1 from Taxonomy 1, however both train and test groups in Project 4 had a statistically significantly higher F1-score than the corresponding groups in Project 1 (P = 0.025 and 0.005, respectively). The results showed that the new taxonomy developed based on cytology and pathology has an overall better performance on predictive effect of skin disease than the ICD-10 on Diseases of the skin and subcutaneous tissue. The level 5 (Project 4) of Taxonomy 2 is better on extension to unknown data of diagnosis system assisted by AI compared to current used classification system from ICD-10, and may have the potential application value in clinic of dermatology.
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http://dx.doi.org/10.1038/s41598-021-92848-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253798PMC
July 2021

Analysis of Mechanical Properties and Mechanism of Natural Rubber Waterstop after Aging in Low-Temperature Environment.

Polymers (Basel) 2021 Jun 28;13(13). Epub 2021 Jun 28.

College of Mechanics and Materials, Hohai University, Nanjing 210098, China.

In order to elucidate the aging performance and aging mechanism of a rubber waterstop in low-temperature environments, the rubber waterstops were placed in the freezing test chamber to accelerate aging, and then we tested its tensile strength, elongation, tear strength, compression permanent deformation and hardness at different times. Additionally, the damaged specimens were tested by scanning electron microscope, Fourier transform infrared spectroscopy and energy dispersive spectrometry. The results showed that with the growth of aging time, the mechanical properties of the rubber waterstop are reduced. At the same time, many protrusions appeared on the surface of the rubber waterstop, the C element gradually decreased, and the O element gradually increased. During the period of 72-90 days, the content of the C element in the low-temperature air environment significantly decreased compared with that in low-temperature water, while the content of O element increased significantly.
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http://dx.doi.org/10.3390/polym13132119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271995PMC
June 2021

Structural design of tetravalent T-cell engaging bispecific antibodies: improve developability by engineering disulfide bonds.

J Biol Eng 2021 Jun 29;15(1):18. Epub 2021 Jun 29.

Key Laboratory of Biorheological Science and Technology (Ministry of Education), Chongqing University, No. 174 Shazheng Street, Shapingba District, 400044, Chongqing, China.

Since the advances in protein engineering and manufacture, over the last 30 years, antibody-based immunotherapeutic has become a powerful strategy to treat diseases. The T-cell engaging bispecific antibody (BsAb) by combining the Fab binding domain of tumor antigens and Fab or single-chain variable fragments (scFvs) binding domain of CD3 molecules, could redirect cytotoxic T cells to kill tumor cells. The IgG-scFv format of BsAb is a dual bivalent and asymmetrical design, which adds the benefit of potent cytotoxicity and less complicated for manufacture but limits the stability and production. Here, we engineered a series of interchain disulfide bonds in the Fab region of IgG-svFv BsAbs and evaluated its biophysical and biological properties. We found that simultaneously replaced the position of VH-VL and CH1-CL residues with cysteine, to form two additional disulfide bonds, could markedly increase monomeric BsAb formation and yield. The thermostability and stability against aggregation and degradation also performed better than BsAbs without extra disulfide bonds introduction. Besides, the affinity of engineered BsAbs was maintained, and the h8B-BsAb antibody had a slight enhancement in an inhibitory effect on target cells.
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http://dx.doi.org/10.1186/s13036-021-00272-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243740PMC
June 2021

Discontinuation Rate of Newly Prescribed Donepezil in Alzheimer's Disease Patients in Asia.

J Clin Neurol 2021 Jul;17(3):376-384

Department of Neurology, Seoul National University College of Medicine & Clinical Neuroscience Center, Seoul National University Bundang Hospital, Seongnam, Korea.

Background And Purpose: The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer's disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia.

Methods: This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50-90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation, treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS).

Results: Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test-Black and White scores, whereas the Clinical Dementia Rating score increased significantly (<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS.

Conclusions: In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.
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http://dx.doi.org/10.3988/jcn.2021.17.3.376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242303PMC
July 2021

Repeated use of SSRIs potentially associated with an increase on serum CK and CK-MB in patients with major depressive disorder: a retrospective study.

Sci Rep 2021 Jun 28;11(1):13365. Epub 2021 Jun 28.

Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), No. 36, Mingxin Road, Liwan District, Guangzhou, 510370, Guangdong, China.

There is a large amount of evidence that selective serotonin reuptake inhibitors (SSRIs) are related to cardiovascular toxicity, which has aroused concern regarding their safety. However, few studies have evaluated the effects of SSRIs on cardiac injury biomarkers, such as creatine kinase (CK) and creatine kinase isoenzyme (CK-MB). The purpose of our study was to determine whether SSRIs elevated CK and CK-MB levels of prior medicated depressive patients (PMDP) compared to first-episode drug-naïve depressive patients (FDDPs). We performed an observational and retrospective study involving 128 patients with major depressive disorder. Patients who had never used any type of antidepressant were designated FDDP; patients who had used only one type of SSRI but were not treated after a recent relapse were designated PMDP. Serum CK and CK-MB levels were measured before and after using SSRIs for a period of time. The duration of current treatment in the FDDP and PMDP groups was 16.200 ± 16.726 weeks and 15.618 ± 16.902 weeks, respectively. After SSRI treatment, levels of serum CK in the PMDP group were significantly higher than in the FDDP group. Univariate ANCOVA results revealed that PMDP was 22.313 times more likely to elevate CK (OR 22.313, 95% CI 9.605-35.022) and 2.615 times more likely to elevate CK-MB (OR 2.615, 95% CI 1.287-3.943) than FDDP. Multivariate ANCOVA revealed an interaction between the group and sex of CK and CK-MB. Further pairwise analysis of the interaction results showed that in female patients, the mean difference (MD) of CK and CK-MB in PMDP was significantly greater than that in FDDP (MD = 33.410, P = 0.000, 95% CI 15.935-50.886; MD = 4.613, P = 0.000, 95% CI 2.846-6.381). Our findings suggest that patients, especially females, who had previously used SSRI antidepressants were more likely to have elevated CK and CK-MB, indicators of myocardial muscle injury. Use of SSRIs should not be assumed to be completely safe and without any cardiovascular risks.
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http://dx.doi.org/10.1038/s41598-021-92807-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239012PMC
June 2021

Biomechanical comparison of screw, tightrope and novel double endobutton in the treatment of tibiofibular syndesmotic injuries.

Injury 2021 Jun 18. Epub 2021 Jun 18.

Department of Orthopedics, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China, 646000; Center for Orthopedic Diseases Research, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou,China, 646000; Expert Workstation in Luzhou, Luzhou, Sichuan, China, 646000; Clinical Base of Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Guangdong Province Medical 3D Printing Application Transformation Engineering Technology Research Center, Luzhou, China, 646000. Electronic address:

Background: Adequate reduction and stabilization of the syndesmosis are significant to prevent early degeneration of the ankle joint and get better clinical outcomes. However, the routine surgical methods have diffierent limitations. The purpose of this study was to develop a novel double Endobutton fixation to treat the distal tibiofibular syndesmotic injuries, and determine whether the novel double Endobutton fixation demonstrates a better biomechanical property compare with the intact syndesmosis, the screw fixation and the Tightrope fixation.

Methods: Twenty-four normal fresh-frozen ankle specimens with a mean age of 42 ± 8 (range, 28-62) years were randomly divided equally into four groups: (1) the intact group, (2) the screw group, (3) the Tightrope group, (4) the Endobutton group. 3D printer technology was used to establish the personalized distal tibiofibular syndesmotic navigation modules to determine the accurate bone tunnel. Axial loading was applied in five ankle positions: neutral position, dorsiflexion, plantar flexion, varus and valgus. Rotation torque was applied in two ankle rotation of the neutral position: internal and external.

Results: In most situations, the displacements of the intact group were larger than the screw group, the Tightrope group and the Endobutton group (P < .05), and the displacements of the screw group were smaller than other three groups (P < .05). The displacements of the double Endobutton group were slightly larger than the Tightrope group but no significant differences were found between these two groups except in the dorsiflexion position of axial loading experiments (P < .05). The novel double Endobutton fixation was steadier than intact syndesmosis and more micromotional than screw fixation.

Conclusion: Our study demonstrated that the novel double Endobutton can be considered as the better fixation in treatment of distal tibiofibular syndesmotic injuries.

Level Of Evidence: Level III, retrospective comparative study.
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http://dx.doi.org/10.1016/j.injury.2021.06.011DOI Listing
June 2021

Single cell imaging reveals cisplatin regulating interactions between transcription (co)factors and DNA.

Chem Sci 2021 Feb 25;12(15):5419-5429. Epub 2021 Feb 25.

Beijing National Laboratory for Molecular Sciences, CAS Research/Education Center for Excellence in Molecular Sciences, National Centre for Mass Spectrometry in Beijing, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences Beijing 100190 People's Republic of China

Cisplatin is an extremely successful anticancer drug, and is commonly thought to target DNA. However, the way in which cisplatin-induced DNA lesions regulate interactions between transcription factors/cofactors and genomic DNA remains unclear. Herein, we developed a dual-modal microscopy imaging strategy to investigate, , the formation of ternary binding complexes of the transcription cofactor HMGB1 and transcription factor Smad3 with cisplatin crosslinked DNA in single cells. We utilized confocal microscopy imaging to map EYFP-fused HMGB1 and fluorescent dye-stained DNA in single cells, followed by the visualization of cisplatin using high spatial resolution (200-350 nm) time of flight secondary ion mass spectrometry (ToF-SIMS) imaging of the same cells. The superposition of the fluorescence and the mass spectrometry (MS) signals indicate the formation of HMGB1-Pt-DNA ternary complexes in the cells. More significantly, for the first time, similar integrated imaging revealed that the cisplatin lesions at Smad-binding elements, for example GGC(GC)/(CG) and AGAC, disrupted the interactions of Smad3 with DNA, which was evidenced by the remarkable reduction in the expression of Smad-specific luciferase reporters subjected to cisplatin treatment. This finding suggests that Smad3 and its related signalling pathway are most likely involved in the intracellular response to cisplatin induced DNA damage.
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http://dx.doi.org/10.1039/d0sc06760aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179581PMC
February 2021

Biological sealing and integration of a fibrinogen-modified titanium alloy with soft and hard tissues in a rat model.

Biomater Sci 2021 Jun 23. Epub 2021 Jun 23.

State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200438, China.

Percutaneous or transcutaneous devices are important and unique, and the corresponding biological sealing at the skin-implant interface is the key to their long-term success. Herein, we investigated the surface modification to enhance biological sealing, using a metal sheet and screw bonded by biomacromolecule fibrinogen mediated via pre-deposited synthetic macromolecule polydopamine (PDA) as a demonstration. We examined the effects of a Ti-6Al-4V titanium alloy modified with fibrinogen (Ti-Fg), PDA (Ti-PDA) or their combination (Ti-PDA-Fg) on the biological sealing and integration with skin and bone tissues. Human epidermal keratinocytes (HaCaT), human foreskin fibroblasts (HFF) and preosteoblasts (MC3T3-E1), which are closely related to percutaneous implants, exhibited better adhesion and spreading on all the three modified sheets compared with the unmodified alloy. After three-week subcutaneous implantation in Sprague-Dawley (SD) rats, the Ti-PDA-Fg sheets could significantly attenuate the soft tissue response and promote angiogenesis compared with other groups. Furthermore, in the model of percutaneous tibial implantation in SD rats, the Ti-PDA-Fg screws dramatically inhibited epithelial downgrowth and promoted new bone formation. Hence, the covalent immobilization of fibrinogen through the precoating of PDA is promising for enhanced biological sealing and osseointegration of metal implants with soft and hard tissues, which is critical for an orthopedic percutaneous medical device.
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http://dx.doi.org/10.1039/d1bm00762aDOI Listing
June 2021

Succession of marine bacteria in response to Ulva prolifera-derived dissolved organic matter.

Environ Int 2021 Oct 15;155:106687. Epub 2021 Jun 15.

College of Marine Life Sciences, and Frontiers Science Center for Deep Ocean Multispheres and Earth System, Ocean University of China, Qingdao 266003, China; Laboratory for Marine Ecology and Environmental Science, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China; Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao 266003, China. Electronic address:

Increasing macroalgal blooms as a consequence of climate warming and coastal eutrophication have profound effects on the marine environment. The outbreaks of Ulva prolifera in the Yellow Sea of China occurring every summer since 2007 to present have formed the world's largest green tide. The green tide releases huge amounts of dissolved organic matter (DOM) to the seawater, causing an organic overload. However, how marine bacteria respond to this issue and the potential impact on the marine environment are still unclear. Here, we monitored the highly temporally resolved dynamics of marine bacterial community that occur in response to Ulva prolifera-derived DOM by performing a 168-h microcosm incubation experiment. DOM inputs significantly increased bacterial abundances within 6 h, decreased bacterial diversity and triggered clear community successions during the whole period of incubation. Vibrio of Gammaproteobacteria robustly and rapidly grew over short timescales (6-24 h), with its relative abundance accounting for up to 52.5% of active bacteria. From 24 to 48 h, some genera of Flavobacteriia grew rapidly, which was more conspicuous at a higher DOM concentration than at a lower concentration. The genus Donghicola of Alphaproteobacteria was predominant at later time points (>48 h). This bacterial community succession was accompanied by significant variations in the activity of 12 different extracellular enzymes, resulting in a rapid reduction of dissolved organic carbon by 74.5% within the first 36 h. In summary, our study demonstrates rapid successions of bacterial community and extracellular enzyme activity after DOM inputs, suggesting that the bacterial response to Ulva prolifera-derived organic matter may contribute to environmental restoration and may pose a health threat due to the bloom of potential pathogenic Vibrio.
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http://dx.doi.org/10.1016/j.envint.2021.106687DOI Listing
October 2021

Injectable and thermosensitive hydrogels mediating a universal macromolecular contrast agent with radiopacity for noninvasive imaging of deep tissues.

Bioact Mater 2021 Dec 23;6(12):4717-4728. Epub 2021 May 23.

State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Shanghai Stomatological Hospital, Fudan University, Shanghai, 200438, China.

It is very challenging to visualize implantable medical devices made of biodegradable polymers in deep tissues. Herein, we designed a novel macromolecular contrast agent with ultrahigh radiopacity (iodinate content > 50%) via polymerizing an iodinated trimethylene carbonate monomer into the two ends of poly(ethylene glycol) (PEG). A set of thermosensitive and biodegradable polyester-PEG-polyester triblock copolymers with varied polyester compositions synthesized by us, which were soluble in water at room temperature and could spontaneously form hydrogels at body temperature, were selected as the demonstration materials. The addition of macromolecular contrast agent did not obviously compromise the injectability and thermogelation properties of polymeric hydrogels, but conferred them with excellent X-ray opacity, enabling visualization of the hydrogels at clinically relevant depths through X-ray fluoroscopy or Micro-CT. In a mouse model, the 3D morphology of the radiopaque hydrogels after injection into different target sites was visible using Micro-CT imaging, and their injection volume could be accurately obtained. Furthermore, the subcutaneous degradation process of a radiopaque hydrogel could be non-invasively monitored in a real-time and quantitative manner. In particular, the corrected degradation curve based on Micro-CT imaging well matched with the degradation profile of virgin polymer hydrogel determined by the gravimetric method. These findings indicate that the macromolecular contrast agent has good universality for the construction of various radiopaque polymer hydrogels, and can nondestructively trace and quantify their degradation . Meanwhile, the present methodology developed by us affords a platform technology for deep tissue imaging of polymeric materials.
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http://dx.doi.org/10.1016/j.bioactmat.2021.05.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165329PMC
December 2021

Increased TIGIT expressing NK cells with dysfunctional phenotype in AML patients correlated with poor prognosis.

Cancer Immunol Immunother 2021 Jun 15. Epub 2021 Jun 15.

The Second Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology; Sino-French Hoffmann Institute, School of Basic Sciences, Guangzhou Medical University, Guangzhou, China.

AML is the most common blood cancer in adults with a high relapse and an overall poor survival rate. NK cells have been demonstrated to have the capacity to eradicate AML blast, and an impaired NK cell function is involved in AML development and progression. Immune checkpoints are involved in immune escape in various cancers. Immune checkpoints blockade therapy mainly aimed to unleash CD8T cells function, but NK cells have emerged as new target. However, immune checkpoints profile on NK cells has not been observed in AML patients. Here, we studied the immune checkpoints expression of NK cells from AML patients at initial diagnosis and found increased PD-1, TIGIT and TIM-3 expression compared to NK cells from healthy donors. Further analysis showed that TIGIT expressing NK cells from AML patients had a dysfunctional phenotype, as TIGITNK cells exhibit lower antileukemia effect, cytokine production and degranulation compared to TIGITNK cells. TIGIT blockade could significantly enhance the function of NK cells. Moreover, AML patients with high frequency of TIGITNK cells had higher frequency of poor prognosis risk. Further analysis found that IL-10 upregulated TIGIT expression on NK cells. Thus, TIGIT blockade alone or in combination with other therapy might be potential strategy to treat AML.
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http://dx.doi.org/10.1007/s00262-021-02978-5DOI Listing
June 2021

Gangrenous Gastritis With Gastric Perforation.

Clin Infect Dis 2021 06;72(12):2241-2243

Department of Infectious Disease, Maimonides Medical Center, Brooklyn, New York, USA.

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http://dx.doi.org/10.1093/cid/ciaa1918DOI Listing
June 2021

Transcriptional Start Site Coverage Analysis in Plasma Cell-Free DNA Reveals Disease Severity and Tissue Specificity of COVID-19 Patients.

Front Genet 2021 28;12:663098. Epub 2021 May 28.

BGI-Shenzhen, Shenzhen, China.

Symptoms of coronavirus disease 2019 (COVID-19) range from asymptomatic to severe pneumonia and death. A deep understanding of the variation of biological characteristics in severe COVID-19 patients is crucial for the detection of individuals at high risk of critical condition for the clinical management of the disease. Herein, by profiling the gene expression spectrum deduced from DNA coverage in regions surrounding transcriptional start site in plasma cell-free DNA (cfDNA) of COVID-19 patients, we deciphered the altered biological processes in the severe cases and demonstrated the feasibility of cfDNA in measuring the COVID-19 progression. The up- and downregulated genes in the plasma of severe patient were found to be closely related to the biological processes and functions affected by COVID-19 progression. More importantly, with the analysis of transcriptome data of blood cells and lung cells from control group and cases with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, we revealed that the upregulated genes were predominantly involved in the viral and antiviral activity in blood cells, reflecting the intense viral replication and the active reaction of immune system in the severe patients. Pathway analysis of downregulated genes in plasma DNA and lung cells also demonstrated the diminished adenosine triphosphate synthesis function in lung cells, which was evidenced to correlate with the severe COVID-19 symptoms, such as a cytokine storm and acute respiratory distress. Overall, this study revealed tissue involvement, provided insights into the mechanism of COVID-19 progression, and highlighted the utility of cfDNA as a noninvasive biomarker for disease severity inspections.
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http://dx.doi.org/10.3389/fgene.2021.663098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194351PMC
May 2021

Genome-Wide Association Study of Kernel Traits in .

Front Genet 2021 28;12:651785. Epub 2021 May 28.

State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Chengdu, China.

is the diploid progenitor of the D subgenome of hexaploid wheat (ivum L.). Here, the phenotypic data of kernel length (KL), kernel width (KW), kernel volume (KV), kernel surface area (KSA), kernel width to length ratio (KWL), and hundred-kernel weight (HKW) for 223 accessions were gathered across three continuous years. Based on population structure analysis, 223 were divided into two subpopulations, namely T-group (mainly included ssp. accessions) and S-group (mainly included ssp. ). Classifications based on cluster analysis were highly consistent with the population structure results. Meanwhile, the extent of linkage disequilibrium decay distance ( = 0.5) was about 110 kb and 290 kb for T-group and S-group, respectively. Furthermore, a genome-wide association analysis was performed on these kernel traits using 6,723 single nucleotide polymorphism (SNP) markers. Sixty-six significant markers, distributed on all seven chromosomes, were identified using a mixed linear model explaining 4.82-13.36% of the phenotypic variations. Among them, 15, 28, 22, 14, 21, and 13 SNPs were identified for KL, KW, KV, KSA, KWL, and HKW, respectively. Moreover, six candidate genes that may control kernel traits were identified (, and ). The transfer of beneficial genes from to wheat using marker-assisted selection will broaden the wheat D subgenome improve the efficiency of breeding.
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http://dx.doi.org/10.3389/fgene.2021.651785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194309PMC
May 2021

Genetic characterizations of spp. from pet rodents indicate high zoonotic potential of pathogens from chinchillas.

One Health 2021 Dec 24;13:100269. Epub 2021 May 24.

Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.

spp. are common protozoan pathogens in mammals. With pet rodents being integrated into modern life, the potential roles of them in transmitting parasites to humans need assessments. In the present study, we examined the occurrence of spp. in pet rodents in Guangdong, south China. A total of 697 fecal samples were collected from 11 species of rodents in seven pet shops, one pet market and one farm. spp. were identified by PCR analysis of the small subunit rRNA gene. An overall infection rate of 36.9% (257/697) was obtained, with infection rates varying from 9.3% in chinchillas, 52.3% in guinea pigs, 57.1% in squirrels, to 68.4% in cricetid animals. Nine species and genotypes were identified, including (in 129 guinea pigs), (in 34 hamsters), (in 32 guinea pigs), hamster genotype (in 30 hamsters), (in 24 chinchillas and squirrels), (in 2 chinchillas), ferret genotype (in 2 chipmunks), (in 1 hamster and 1 guinea pig), and chipmunk genotype V (in 1 chinchilla and 1 chipmunk). Sequence analysis of the 60 kDa glycoprotein gene identified three subtype families of , including family XIId in 15 chinchillas, XIIa in 5 chinchillas, and a new subtype family (XIIi) in 1 squirrel. The identification of and in pet rodents suggests that these animals, especially chinchillas, could serve as reservoirs of human-pathogenic spp. Hygiene should be practiced in the rear and care of these animals, and One Health measures should be developed to reduce the occurrence of zoonotic infections due to contact with pet rodents.
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http://dx.doi.org/10.1016/j.onehlt.2021.100269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170418PMC
December 2021

Role of krüppel-like factor 8 for therapeutic drug-resistant multi-organ metastasis of breast cancer.

Am J Cancer Res 2021 15;11(5):2188-2201. Epub 2021 May 15.

Burnett School of Biomedical Sciences University of Central Florida College of Medicine 6900 Lake Nona Boulevard, Orlando, FL 32827, USA.

Metastasis and drug resistance are intertwined processes that are responsible for the vast majority of patient deaths from breast cancer. The underlying mechanisms remain incompletely understood. We previously demonstrated that KLF8 activates CXCR4 transcription in metastatic breast cancer. Here, we report a novel role of KLF8-CXCR4 signaling for converting single organ metastasis into multiple organ metastasis associated with chemotherapeutic resistance. We show that KLF8 expression in metastatic breast cancer cells can be over-induced by chemotherapeutic drugs. Analysis of data from large-cohorts of patients indicates that post-chemotherapy there is a close correlation between the aberrant high levels of KLF8 and CXCR4 and that this correlation is well associated with drug resistance, metastasis, and poor prognosis. To mimic their aberrant high levels, we overexpressed KLF8 or CXCR4 in a human breast cancer cell line known to metastasize only to the lungs after intravenous injection in nude mice. As expected, these cells become more resistant to chemotherapeutic drugs. Surprisingly, these KLF8 or CXCR4 overexpressing cells, even implanted orthotopically, metastasized extensively to multiple organs particularly the CXCL12-rich organs. Tube formation assay, Ki67 staining and Western blotting revealed that KLF8 or CXCR4 overexpression enhanced angiogenesis involving increased expression and secretion of VEGF protein. We also found that KLF8 or CXCR4 overexpression strongly enhanced formation of filopodium-like protrusions and proliferation via CXCR4 stimulation in a 3D culture model mimicking the colonization step of metastasis. Taken together, these results suggest that the chemo-induction of KLF8 upregulation be critical for drug resistance and systemic metastasis through enhanced tumor angiogenesis and colonization via CXCR4 over-activation and that KLF8-CXCR4 signaling axis may be a new therapeutic target for drug-resistant breast cancer metastasis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167685PMC
May 2021

Palladium-catalyzed hydroalkylation of methylenecyclopropanes with simple hydrazones.

Chem Sci 2020 May 15;11(39):10759-10763. Epub 2020 May 15.

Department of Chemistry, FQRNT Centre for Green Chemistry and Catalysis, McGill University 801 Sherbrooke St. W. Montreal Quebec H3A 0B8 Canada

A palladium-catalyzed hydroalkylation reaction of methylenecyclopropanes highly selective C-C σ-bond scission was achieved under mild conditions, in which simple hydrazones served as carbanion equivalents. This method featured good functional group compatibility, affording high yields of C-alkylated terminal alkenes.
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http://dx.doi.org/10.1039/d0sc01221aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162302PMC
May 2020

Decoding Spatial Memory Retrieval in Cubical Space Using fMRI Signals.

Front Neural Circuits 2021 18;15:624352. Epub 2021 May 18.

Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.

The way spatial memory retrieval is represented in the brain remains unclear to date. Previous studies have displayed a hippocampus-centered navigation network using functional magnetic resonance imaging (fMRI) analysis. There have been some studies on the representation of navigation behavior by signal distribution patterns, but only in the hippocampus and adjacent structures. In this study, we aimed to determine (1) the brain regions that represent information in both intensity and distribution patterns during spatial memory retrieval and (2) whether the patterns of neural responses represent spatial memory retrieval behavior performance. Both univariate analysis [general linear model (GLM)] and multivariate pattern analysis (MVPA) were employed to reveal the spatial distributions of brain responses elicited by spatial memory retrieval. Correlation analyses were performed to detect the correspondences between brain responses and behavior performance. We found that spatial memory retrieval occurred in widespread brain regions, including the bilateral hippocampi, bilateral superior frontal gyrus, bilateral superior parietal lobules, bilateral occipital lobes, and cerebellum. The amplitude of activation in the left hippocampus showed a significant negative correlation ( = -0.46, = 0.039) with the number of task completions. Additionally, within-subject classification accuracies based on the blood oxygenation level-dependent (BOLD) signal patterns of the right middle temporal gyrus (rMTG) rostral areas in the Brainnetome Atlas showed a significant positive correlation ( = 0.78, < 0.0001) with retrieval accuracy. In summary, our findings have implications for understanding the separation between navigational and non-navigational states and emphasizing the utility of MVPA in the whole brain.
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http://dx.doi.org/10.3389/fncir.2021.624352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168467PMC
May 2021

Establishment of anti-oxidation platform based on few-layer molybdenum disulfide nanosheet-coated titanium dioxide nanobelt nanocomposite.

J Colloid Interface Sci 2021 May 18;601:167-176. Epub 2021 May 18.

Institute of Biomedical Engineering, College of Life Sciences, Qingdao University, Qingdao 266071, China; Department of Urology, Key Laboratory of Urinary System Diseases, The Affiliated Hospital of Qingdao University, Qingdao 266003, China. Electronic address:

The nanozyme-based antioxidant system could protect normal cells from oxidative stress due to their reactive oxygen species (ROS) scavenging activity and good chemical stability. However, its use is limited for practical in vivo applications due to the high cost and poor biocompatibility (low catalytic efficiency). Herein, MoS decorated on TiO nanobelts ([email protected]) was prepared for antioxidation applications. The as-prepared [email protected] heterostructure with 50 wt% MoS showed the highest efficient catalase activity and superoxide dismutase (SOD) activity under normal physiological conditions. The composite was superior to its single component in terms of enhanced dispersibility and catalytic performance resulting from the higher surface specific area and more exposed active sites. [email protected] was not only confirmed to have good in vitro and in vivo biocompatibility but can also effectively eliminate the endogenous excessive accumulation of ROS caused by oxidative stress using the fibroblast cell (L929) line as a model. Further experiments confirmed that in the established mouse oxidative stress model, [email protected] can quickly restore the ROS to a normal level in the oxidative stress site of the mouse. These results indicated that [email protected] enzyme-like nanomaterials can provide a huge therapeutic potential in future antioxidant defence applications.
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http://dx.doi.org/10.1016/j.jcis.2021.05.056DOI Listing
May 2021

Comparison of the Efficacy of Minimally Invasive and Open Surgery on Children with Neuroblastoma: A Meta-Analysis.

J Laparoendosc Adv Surg Tech A 2021 Jul 1;31(7):829-838. Epub 2021 Jun 1.

Department of Pediatric Surgery, Fujian Province Maternal and Child Health Hospital, Fuzhou, China.

Evaluate the clinical efficacy and safety of minimally invasive surgery (MIS) and open surgery in the treatment of neuroblastoma (NB) in children by a meta-analysis. This is a meta-analysis. We searched for random or nonrandomized controlled study of MIS group and OPEN surgery group for the treatment of childhood NB included in PubMed, ClinicalTrials, EMBASE, and Cochrane library before January 31, 2020. Data extraction was performed in a standard format for the included studies, including tumor diameter, operation time, intraoperative bleeding, length of hospital stay (LOHS), complications, recurrence, and MYCN. Seven retrospective studies were finally included, with a total of 571 children, including 162 in MIS group and 409 in the OPEN surgery group. Compared with the OPEN surgery group, the MIS group had reduced intraoperative bleeding (mean difference [MD] = -12.72, 95% CI: -24.84 to -0.61,  < .05), and reduced l LOHS (MD = -3.35, 95% CI: -5.55 to -1.15,  < .05) and decreased postoperative recurrence (MD = 0.20, 95% CI: 0.05-0.75,  < .05). The differences between the groups were statistically significant. There was no significant difference between groups in tumor diameter (MD = -18.84, 95% CI: -48.12 to 10.43,  > .05), operation time (MD = -21.7, 95% CI: -97.52 to 54.13,  > .05), and MYCN results (odds ratio = 2.27, 95% CI: 0.56-9.18,  > .05). Preliminary evidence indicates that the treatment of NB with MIS has the advantages of less intraoperative bleeding, shorter LOHS, and less postoperative recurrence compared with open surgery.
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http://dx.doi.org/10.1089/lap.2020.0618DOI Listing
July 2021

Metabolic reprogramming of myeloid-derived suppressor cells: An innovative approach confronting challenges.

J Leukoc Biol 2021 Jun 2. Epub 2021 Jun 2.

Bone Marrow Transplantation Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

Immune cells such as T cells, macrophages, dendritic cells, and other immunoregulatory cells undergo metabolic reprogramming in cancer and inflammation-derived microenvironment to meet specific physiologic and functional demands. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that are characterized by immunosuppressive activity, which plays a key role in host immune homeostasis. In this review, we have discussed the core metabolic pathways, including glycolysis, lipid and fatty acid biosynthesis, and amino acid metabolism in the MDSCs under various pathologic situations. Metabolic reprogramming is a determinant of the phenotype and functions of MDSCs, and is therefore a novel therapeutic possibility in various diseases.
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http://dx.doi.org/10.1002/JLB.1MR0421-597RRDOI Listing
June 2021

Online Movement Correction in Response to the Unexpectedly Perturbed Initial or Final Action Goals: An ERP and sLORETA Study.

Brain Sci 2021 May 15;11(5). Epub 2021 May 15.

Neurocognition and Action-Biomechanics Research Group, Faculty of Psychology and Sports Science, Bielefeld University, 33501 Bielefeld, Germany.

In this experiment, we explored how unexpected perturbations in the initial (grip posture) and the final action goals (target position) influence movement execution and the neural mechanisms underlying the movement corrections. Participants were instructed to grasp a handle and rotate it to a target position according to a given visual cue. After participants started their movements, a secondary cue was triggered, which indicated whether the initial or final goals had changed (or not) while the electroencephalogram (EEG) was recorded. The results showed that the perturbed initial goals significantly slowed down the reaching action, compared to the perturbed final goals. In the event-related potentials (ERPs), a larger anterior P3 and a larger central-distributed late positivity (600-700 ms) time-locked to the perturbations were found for the initial than for the final goal perturbations. Source analyses found stronger left middle frontal gyrus (MFG) activations for the perturbed initial goals than for the perturbed final goals in the P3 time window. These findings suggest that perturbations in the initial goals have stronger interferences with the execution of grasp-to-rotate movements than perturbations in the final goals. The interferences seem to be derived from both inappropriate action inhibitions and new action implementations during the movement correction.
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http://dx.doi.org/10.3390/brainsci11050641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156469PMC
May 2021

Preliminary investigation of the associations between psychological flexibility, symptoms and daily functioning in people with chronic abdominal pain.

Br J Pain 2021 May 3;15(2):175-186. Epub 2020 Jun 3.

Pain Management Centre, Guy's and St Thomas' NHS Foundation Trust, London, UK.

Objective: Acceptance and commitment therapy (ACT), based in the psychological flexibility model, may benefit people with chronic abdominal pain. The current study preliminarily investigates associations between psychological flexibility processes and daily general, social and emotional functioning in chronic abdominal pain.

Methods: An online survey comprising measures of psychological flexibility processes and daily functioning was distributed through social media.

Subjects: In total, 89 participants with chronic abdominal pain were included in the analyses.

Results: All investigated psychological flexibility processes significantly correlated with pain interference, work and social adjustment, and depression, in the expected directions (|r| = .35-.68). Only pain acceptance significantly correlated with gastrointestinal (GI) symptoms, r = -.25. After adjusting for pain in the analyses, pain acceptance remained significantly associated with all outcomes, |β| = .28-.56, but depression. After adjusting for pain and pain acceptance, only cognitive fusion remained significantly associated with anxiety, β = -.27, and depression, β = .43. When contrasting GI-specific anxiety with psychological flexibility processes, pain acceptance was uniquely associated with pain-related interference and work and social adjustment, and cognitive fusion and committed action were uniquely associated with depression.

Conclusions: Psychological flexibility processes were positively associated with daily functioning in people with chronic abdominal pain. ACT may provide benefit for these people. Further studies with experimental designs are needed to examine the utility of ACT for people with abdominal pain.
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http://dx.doi.org/10.1177/2049463720926559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138614PMC
May 2021

MultiTrans: an algorithm for path extraction through mixed integer linear programming for transcriptome assembly.

IEEE/ACM Trans Comput Biol Bioinform 2021 May 25;PP. Epub 2021 May 25.

Recent advances in RNA-seq technology have made identification of expressed genes affordable, and thus boosting repaid development of transcriptomic studies. Transcriptome assembly, reconstructing all expressed transcripts from RNA-seq reads, is an essential step to understand genes, proteins, and cell functions. Transcriptome assembly remains a challenging problem due to complications in splicing variants, expression levels, uneven coverage and sequencing errors. Here, we formulate the transcriptome assembly problem as path extraction on splicing graphs (or assembly graphs), and propose a novel algorithm MultiTrans for path extraction using mixed integer linear programming. MultiTrans is able to take into consideration coverage constraints on vertices and edges, the number of paths and the paired-end information simultaneously. We benchmarked MultiTrans against two state-of-the-art transcriptome assemblers, TransLiG and rnaSPAdes. Experimental results show that MultiTrans generates more accurate transcripts compared to TransLiG (using the same splicing graphs) and rnaSPAdes (using the same assembly graphs). MultiTrans is freely available at https://github.com/jzbio/MultiTrans.
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http://dx.doi.org/10.1109/TCBB.2021.3083277DOI Listing
May 2021