Publications by authors named "Yan Chen"

5,679 Publications

  • Page 1 of 1

Bisection Neural Network Toward Reconfigurable Hardware Implementation.

IEEE Trans Neural Netw Learn Syst 2022 Aug 11;PP. Epub 2022 Aug 11.

A hardware-friendly bisection neural network (BNN) topology is proposed in this work for approximately implementing massive pieces of complex functions in arbitrary on-chip configurations. Instead of the conventional reconfigurable fully connected neural network (FC-NN) circuit topology, the proposed hardware-friendly topology performs NN behaviors in a bisection structure, in which each neuron includes two constant synapse connections for both inputs and outputs. Compared with the FC-NN one, the reconfiguration of the BNN circuit topology eliminates the remarkable amount of dummy synapse connections in hardware. As the main target application, this work aims at building a general-purpose BNN circuit topology that offers a great amount of NN regressions. To achieve this target, we prove that the NN behaviors of the FC-NN circuit topologies can be migrated to the BNN circuit topologies equivalently. We introduce two approaches including the refining training algorithm and the inverted-pyramidal strategy to further reduce the number of neurons and synapses. Finally, we conduct the inaccuracy tolerance analysis to suggest the guideline for ultra-efficient hardware implementations. Compared with the state-of-the-art FC-NN circuit topology-based TrueNorth baseline, the proposed design can achieve 17.8-22.2 × hardware reduction and less than 1% inaccuracy.
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http://dx.doi.org/10.1109/TNNLS.2022.3195821DOI Listing
August 2022

Iron quantitative analysis of motor combined with bulbar region in M1 cortex may improve diagnosis performance in ALS.

Eur Radiol 2022 Aug 11. Epub 2022 Aug 11.

Department of Radiology, Huashan Hospital, Fudan University, No. 12 Middle Wulumuqi Road, Jingan District, Shanghai, 200040, China.

Objectives: To explore whether the combined analysis of motor and bulbar region of M1 on susceptibility-weighted imaging (SWI) can be a valid biomarker for amyotrophic lateral sclerosis (ALS).

Methods: Thirty-two non-demented ALS patients and 35 age- and gender-matched healthy controls (HC) were retrospectively recruited. SWI and 3D-T1-MPRAGE images were obtained from all individuals using a 3.0-T MRI scan. The bilateral posterior band of M1 was manually delineated by three neuroradiologists on phase images and subdivided into the motor and bulbar regions. We compared the phase values in two groups and performed a stratification analysis (ALSFRS-R score, duration, disease progression rate, and onset). Receiver operating characteristic (ROC) curves were also constructed.

Results: ALS group showed significantly increased phase values in M1 and the two subregions than the HC group, on the all and elderly level (p < 0.001, respectively). On all-age level comparison, negative correlations were found between phase values of M1 and clinical score and duration (p < 0.05, respectively). Similar associations were found in the motor region (p < 0.05, respectively). On both the total (p < 0.01) and elderly (p < 0.05) levels, there were positive relationships between disease progression rate and M1 phase values. In comparing ROC curves, the entire M1 showed the best diagnostic performance.

Conclusions: Combining motor and bulbar analyses as an integral M1 region on SWI can improve ALS diagnosis performance, especially in the elderly. The phase value could be a valuable biomarker for ALS evaluation.

Key Points: • Integrated analysis of the motor and bulbar as an entire M1 region on SWI can improve the diagnosis performance in ALS. • Quantitative analysis of iron deposition by SWI measurement helps the clinical evaluation, especially for the elderly patients. • Phase value, when combined with the disease progression rate, could be a valuable biomarker for ALS.
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http://dx.doi.org/10.1007/s00330-022-09045-2DOI Listing
August 2022

An Auxiliary Diagnostic System for Parkinson's Disease Based on Wearable Sensors and Genetic Algorithm Optimized Random Forest.

IEEE Trans Neural Syst Rehabil Eng 2022 Aug 10;PP. Epub 2022 Aug 10.

Parkinson's disease (PD) is a neurodegenerative disorder characterized mainly by motor-related impairment, an accurate, quantitative, and objective diagnosis is an effective way to slow the disease deterioration process. In this paper, a user-friendly auxiliary diagnostic system for PD is constructed based on the upper limb movement conditions of 100 subjects consisting of 50 PD patients and 50 healthy subjects. This system includes wearable sensors that collect upper limb movement data, host computer for data processing and classification, and graphic user interface (GUI). The genetic algorithm optimized random forest classifier is introduced to classify PD and normal states based on the selected optimal features, and the 50 trials leave-one-out cross-validation is used to evaluate the performance of the classifier, with the highest accuracy of 94.4%. The classification accuracy among different upper limb movement tasks and with the different number of sensors are compared, results show that the task with only alternation hand movement also has satisfactory classification accuracy, and sensors on both wrists performance better than one sensor on a single wrist. The utility of the proposed system is illustrated by neurologists with a deployed GUI during the clinical inquiry, opening the possibility for a wide range of applications in the auxiliary diagnosis of PD.
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http://dx.doi.org/10.1109/TNSRE.2022.3197807DOI Listing
August 2022

Distinct neural networks derived from galanin-containing nociceptors and neurotensin-expressing pruriceptors.

Proc Natl Acad Sci U S A 2022 Aug 9;119(33):e2118501119. Epub 2022 Aug 9.

Guangdong Institute of Intelligence Science and Technology, 519031 Zhuhai, China.

Pain and itch are distinct sensations arousing evasion and compulsive desire for scratching, respectively. It's unclear whether they could invoke different neural networks in the brain. Here, we use the type 1 herpes simplex virus H129 strain to trace the neural networks derived from two types of dorsal root ganglia (DRG) neurons: one kind of polymodal nociceptors containing galanin () and one type of pruriceptors expressing neurotensin (). The DRG microinjection and immunosuppression were performed in transgenic mice to achieve a successful tracing from specific types of DRG neurons to the primary sensory cortex. About one-third of nuclei in the brain were labeled. More than half of them were differentially labeled in two networks. For the ascending pathways, the spinothalamic tract was absent in the network derived from -expressing pruriceptors, and the two networks shared the spinobulbar projections but occupied different subnuclei. As to the motor systems, more neurons in the primary motor cortex and red nucleus of the somatic motor system participated in the -containing nociceptor-derived network, while more neurons in the nucleus of the solitary tract (NST) and the dorsal motor nucleus of vagus nerve (DMX) of the emotional motor system was found in the -expressing pruriceptor-derived network. Functional validation of differentially labeled nuclei by c-Fos test and chemogenetic inhibition suggested the red nucleus in facilitating the response to noxious heat and the NST/DMX in regulating the histamine-induced scratching. Thus, we reveal the organization of neural networks in a DRG neuron type-dependent manner for processing pain and itch.
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http://dx.doi.org/10.1073/pnas.2118501119DOI Listing
August 2022

D-A type NIR-II Organic Molecules: Strategies for the Enhancement Fluorescence Brightness and Applications in NIR-II Fluorescence Imaging-Navigated Photothermal Therapy.

Adv Healthc Mater 2022 Aug 9:e2201158. Epub 2022 Aug 9.

State Key Laboratory of Bioelectronics, Jiangsu Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, South east University, Dingjiaqiao 87, Nanjing, Jiangsu, 210009, PR China.

NIR-II fluorescence imaging (NIR-II FI) and photothermal therapy (PTT) have received broad attentions in precise tumor diagnosis and effective treatment attributed to high-resolution and deep tissue imaging, negligible invasive, and high-efficiency treatment. Although many fluorescent molecules have been designed and conducted for NIR-II FI and PTT, it is still an enormous challenge for researchers to pioneer some rational design guidelines to improve fluorescence brightness. Organic D-A type molecules, including small molecules and conjugated polymers, can be designed and developed to improve fluorescence brightness due to its tunable and easy functionalized chemical structures, allowing molecules tailored photophysical properties. In this review, some approaches to the development and design strategies of D-A type small molecules and conjugated polymers for the enhancement of fluorescence brightness are systemically introduced. Meanwhile, some applications of PTT and PTT based combination therapy (such as PDT, chemotherapy, or gas therapy) assisted by NIR-II FI based single or multi-imaging technologies were classified and represented in detail as well. Finally, the current issues and challenges of NIR-II organic molecules in NIR-II FI-navigated PTT are summarized and discussed, which gives some guidelines for the future development direction of NIR-II organic molecules for NIR-II FI-navigated PTT. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/adhm.202201158DOI Listing
August 2022

Whole-lesion apparent diffusion coefficient (ADC) histogram as a quantitative biomarker to preoperatively differentiate stage IA endometrial carcinoma from benign endometrial lesions.

BMC Med Imaging 2022 Aug 8;22(1):139. Epub 2022 Aug 8.

Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

Background: To assess the value of whole-lesion apparent diffusion coefficient (ADC) histogram analysis in differentiating stage IA endometrial carcinoma (EC) from benign endometrial lesions (BELs) and characterizing histopathologic features of stage IA EC preoperatively.

Methods: One hundred and six BEL and 126 stage IA EC patients were retrospectively enrolled. Eighteen volumetric histogram parameters were extracted from the ADC map of each lesion. The Mann-Whitney U or Student's t-test was used to compare the differences between the two groups. Models based on clinical parameters and histogram features were established using multivariate logistic regression. Receiver operating characteristic (ROC) analysis and calibration curves were used to assess the models.

Results: Stage IA EC showed lower ADC, ADC, ADC, ADC, ADC, ADC, interquartile range, mean absolute deviation, robust mean absolute deviation (rMAD), root mean squared, energy, total energy, entropy, variance, and higher skewness, kurtosis and uniformity than BELs (all p < 0.05). ADC yielded the highest area under the ROC curve (AUC) of 0.928 (95% confidence interval [CI] 0.895-0.960; cut-off value = 1.161 × 10 mm/s) for differentiating stage IA EC from BELs. Moreover, multivariate analysis demonstrated that ADC-score (ADC + skewness + rMAD + total energy) was the only significant independent predictor (OR = 2.641, 95% CI 2.045-3.411; p < 0.001) for stage IA EC when considering clinical parameters. This ADC histogram model (ADC-score) achieved an AUC of 0.941 and a bias-corrected AUC of 0.937 after bootstrap resampling. The model performed well for both premenopausal (accuracy = 0.871) and postmenopausal (accuracy = 0.905) patients. Besides, ADC and ADC were significantly lower in Grade 3 than in Grade 1/2 stage IA EC (p = 0.022 and 0.047). At the same time, no correlation was found between ADC histogram parameters and the expression of Ki-67 in stage IA EC (all p > 0.05).

Conclusions: Whole-lesion ADC histogram analysis could serve as an imaging biomarker for differentiating stage IA EC from BELs and assisting in tumor grading of stage IA EC, thus facilitating personalized clinical management for premenopausal and postmenopausal patients.
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http://dx.doi.org/10.1186/s12880-022-00864-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9358891PMC
August 2022

DARPP32, a target of hyperactive mTORC1 in the retinal pigment epithelium.

Proc Natl Acad Sci U S A 2022 Aug 8;119(33):e2207489119. Epub 2022 Aug 8.

Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104.

The mechanistic target of rapamycin (mTOR) is assembled into signaling complexes of mTORC1 or mTORC2, and plays key roles in cell metabolism, stress response, and nutrient and growth factor sensing. Accumulating evidence from human and animal model studies has demonstrated a pathogenic role of hyperactive mTORC1 in age-related macular degeneration (AMD). The retinal pigment epithelium (RPE) is a primary injury site in AMD. In mouse models of RPE-specific deletion of Tuberous sclerosis 1 (), which encodes an upstream suppressor of mTORC1, the hyperactivated mTORC1 metabolically reprogrammed the RPE and led to the degeneration of the outer retina and choroid (CH). In the current study, we use single-cell RNA sequencing (scRNA-seq) to identify an RPE mTORC1 downstream protein, dopamine- and cyclic AMP-regulated phosphoprotein of molecular weight 32,000 (DARPP-32). DARPP-32 was not found in healthy RPE but localized to drusen and basal linear deposits in human AMD eyes. In animal models, overexpressing DARPP-32 by adeno-associated virus (AAV) led to abnormal RPE structure and function. The data indicate that DARPP-32 is a previously unidentified signaling protein subjected to mTORC1 regulation and may contribute to RPE degeneration in AMD.
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http://dx.doi.org/10.1073/pnas.2207489119DOI Listing
August 2022

Application of artificial intelligence to pancreatic adenocarcinoma.

Front Oncol 2022 22;12:960056. Epub 2022 Jul 22.

Department of General Surgery, Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, China.

Background And Objectives: Pancreatic cancer (PC) is one of the deadliest cancers worldwide although substantial advancement has been made in its comprehensive treatment. The development of artificial intelligence (AI) technology has allowed its clinical applications to expand remarkably in recent years. Diverse methods and algorithms are employed by AI to extrapolate new data from clinical records to aid in the treatment of PC. In this review, we will summarize AI's use in several aspects of PC diagnosis and therapy, as well as its limits and potential future research avenues.

Methods: We examine the most recent research on the use of AI in PC. The articles are categorized and examined according to the medical task of their algorithm. Two search engines, PubMed and Google Scholar, were used to screen the articles.

Results: Overall, 66 papers published in 2001 and after were selected. Of the four medical tasks (risk assessment, diagnosis, treatment, and prognosis prediction), diagnosis was the most frequently researched, and retrospective single-center studies were the most prevalent. We found that the different medical tasks and algorithms included in the reviewed studies caused the performance of their models to vary greatly. Deep learning algorithms, on the other hand, produced excellent results in all of the subdivisions studied.

Conclusions: AI is a promising tool for helping PC patients and may contribute to improved patient outcomes. The integration of humans and AI in clinical medicine is still in its infancy and requires the in-depth cooperation of multidisciplinary personnel.
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http://dx.doi.org/10.3389/fonc.2022.960056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353734PMC
July 2022

Intramuscular Inoculation of AS02-Adjuvanted Respiratory Syncytial Virus (RSV) F Subunit Vaccine Shows Better Efficiency and Safety Than Subcutaneous Inoculation in BALB/c Mice.

Front Immunol 2022 22;13:938598. Epub 2022 Jul 22.

National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, China.

We previously explored a panel of adjuvants formulated with pre-fusion RSV-F protein and found that AS02 may be a promising candidate adjuvant for developing RSV-F subunit vaccines with improved immunogenicity and desired immune response type. In this study, we performed a head-to-head comparison of the effect of intramuscular injection to that of subcutaneous injection on the immune response and protective efficacy of recombinant RSV-F subunit vaccine with or without adjuvants (Alhydrogel, squalene-based emulsion adjuvants MF59, AS03, and AS02) in BALB/c mice. After inoculations, antigen-specific antibodies, neutralizing antibodies, antibody subtypes, cytokines, and the persistence of immune response were evaluated. Moreover, challenge tests were also performed to illustrate the possible effect of inoculation routes and adjuvant on virus clearance and histochemistry changes in the lungs of mice. The results indicated that intramuscular inoculation is a more effective and antigen dose-sparing route to enhance the immune response, although subcutaneous inoculation induced faster and stronger IgG antibodies after the initial immunization. Furthermore, adjuvant, but not immunization route, is a more critical factor to affect the humoral/cellular immune response and the immune bias. In addition, adjuvant inoculated the intramuscular route is safer than that the subcutaneous route, especially for AS02. This study highlights the importance of the adjuvant and immunization routes in the design and clinical transformation of adjuvanted vaccines. Further investigation is needed to illustrate the mechanism underlying the above difference in both efficiency and safety.
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http://dx.doi.org/10.3389/fimmu.2022.938598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354885PMC
August 2022

Specnuezhenide suppresses diabetes-induced bone loss by inhibiting RANKL-induced osteoclastogenesis.

Acta Biochim Biophys Sin (Shanghai) 2022 Jul 25. Epub 2022 Jul 25.

Diabetes osteoporosis is a chronic complication of diabetes mellitus (DM) and is associated with osteoclast formation and enhanced bone resorption. Specnuezhenide (SPN) is an active compound with anti-inflammatory and immunomodulatory properties. However, the roles of SPN in diabetic osteoporosis remain unknown. In this study, primary bone marrow macrophages (BMMs) were pretreated with SPN and were stimulated with receptor activator of nuclear factor kappa B ligand (RANKL; to induce osteoclastogenesis. The number of osteoclasts was detected by tartrate-resistant acid phosphatase (TRAP) staining. The protein levels of cellular oncogene fos/nuclear factor of activated T cells c1 (c-Fos/NFATc1), nuclear factor kappa-B (NF-κB), and mitogen-activated protein kinases (MAPKs) were evaluated by western blot analysis. NF-κB luciferase assays were used to examine the role of SPN in NF-κB activation. The DM model group received a high-glucose, high-fat diet and was then intraperitoneally injected with streptozotocin (STZ). Micro-CT scanning, serum biochemical analysis, histological analysis were used to assess bone loss. We found that SPN suppressed RANKL-induced osteoclast formation and that SPN inhibited the expression of osteoclast-related genes and c-Fos/NFATc1. SPN inhibited RANKL-induced activation of NF-κB and MAPKs. In vivo experiments revealed that SPN suppressed diabetes-induced bone loss and the number of osteoclasts. Furthermore, SPN decreased the levels of bone turnover markers and increased the levels of runt-related transcription factor 2 (RUNX2), osteoprotegerin (OPG), calcium (Ca) and phosphorus (P). SPN also regulated diabetes-related markers. This study suggests that SPN suppresses diabetes-induced bone loss by inhibiting RANKL-induced osteoclastogenesis, and provides an experimental basis for the treatment of diabetic osteoporosis.
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http://dx.doi.org/10.3724/abbs.2022094DOI Listing
July 2022

Microbial diversity and adaptive strategies in the Mars-like Qaidam Basin, North Tibetan Plateau, China.

Environ Microbiol Rep 2022 Aug 4. Epub 2022 Aug 4.

Key Laboratory of Earth and Planetary Physics, Institute of Geology and Geophysics, Chinese Academy of Sciences, Beijing, China.

The Qaidam Basin on the northern Tibetan Plateau, China, is one of the driest deserts at high elevations, and it has been considered a representative Mars analogue site. Despite recent advances in the diversity of microbial communities in the Qaidam Basin, our understanding of their genomic information, functional potential and adaptive strategies remains very limited. Here, we conducted a combination of physicochemical and metagenomic analyses to investigate the taxonomic composition and adaptive strategies of microbial life in the regolith across the Qaidam Basin. 16S ribosomal RNA (rRNA) gene-based and metagenomic analyses both reveal that microbial communities in the Qaidam Basin are dominated by the bacterial phylum Actinobacteria. The low levels of moisture and organic carbon contents appear to have essential constraints on microbial biomass and diversity. A total of 50 high-quality metagenome-assembled genomes were reconstructed and analysed. Our results reveal the potential of microorganisms to use ambient trace gases to meet energy and carbon needs in this nutrient-limited desert. Furthermore, we find that DNA repair mechanisms and protein protection are likely essential for microbial life in response to stressors of hyperaridity, intense ultraviolet radiation and tremendous temperature fluctuations in this Mars analogue. These findings shed light on the diversity and survival strategies of microbial life inhabiting Mar-like environments, which provide implications for potential life on early Mars.
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http://dx.doi.org/10.1111/1758-2229.13111DOI Listing
August 2022

Evaluation of a Functional Single Nucleotide Polymorphism of the SARS-CoV-2 Receptor That Is Potentially Involved in Long COVID.

Front Genet 2022 18;13:931562. Epub 2022 Jul 18.

Center for Applied Bioinformatics, St. Jude Children's Research Hospital, Memphis, TN, United States.

Since the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, SARS-CoV-2 has led to a global coronavirus disease 2019 (COVID-19) pandemic. A better understanding of the SARS-CoV-2 receptor at the genetic level would help combat COVID-19, particularly for long COVID. We performed a genetic analysis of and searched for its common potential single nucleotide polymorphisms (SNPs) with minor allele frequency >0.05 in both European and Chinese populations that would contribute to gene expression variation. We thought that the variation of the expression would be an important biological feature that would strongly affect COVID-19 symptoms, such as "brain fog", which is highlighted by the fact that ACE2 acts as a major cellular receptor for SARS-CoV-2 attachment and is highly expressed in brain tissues. Based on the human GTEx gene expression database, we found rs2106809 exhibited a significant correlation with the expression among multiple brain and artery tissues. This expression correlation was replicated in an independent European brain eQTL database, Braineac. rs2106809*G also displays significantly higher frequency in Asian populations than in Europeans and displays a protective effect ( = 0.047) against COVID-19 hospitalization when comparing hospitalized COVID-19 cases with non-hospitalized COVID-19 or SARS-CoV-2 test-negative samples with European ancestry from the UK Biobank. Furthermore, we experimentally demonstrated that rs2106809*G could upregulate the transcriptional activity of . Therefore, integrative analysis and functional experiment strongly support that SNP rs2106809 is a functional brain eQTL and its potential involvement in long COVID, which warrants further investigation.
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http://dx.doi.org/10.3389/fgene.2022.931562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9340221PMC
July 2022

Strong yet ductile nanolamellar high-entropy alloys by additive manufacturing.

Nature 2022 08 3;608(7921):62-68. Epub 2022 Aug 3.

Department of Mechanical and Industrial Engineering, University of Massachusetts, Amherst, MA, USA.

Additive manufacturing produces net-shaped components layer by layer for engineering applications. The additive manufacture of metal alloys by laser powder bed fusion (L-PBF) involves large temperature gradients and rapid cooling, which enables microstructural refinement at the nanoscale to achieve high strength. However, high-strength nanostructured alloys produced by laser additive manufacturing often have limited ductility. Here we use L-PBF to print dual-phase nanolamellar high-entropy alloys (HEAs) of AlCoCrFeNi that exhibit a combination of a high yield strength of about 1.3 gigapascals and a large uniform elongation of about 14 per cent, which surpasses those of other state-of-the-art additively manufactured metal alloys. The high yield strength stems from the strong strengthening effects of the dual-phase structures that consist of alternating face-centred cubic and body-centred cubic nanolamellae; the body-centred cubic nanolamellae exhibit higher strengths and higher hardening rates than the face-centred cubic nanolamellae. The large tensile ductility arises owing to the high work-hardening capability of the as-printed hierarchical microstructures in the form of dual-phase nanolamellae embedded in microscale eutectic colonies, which have nearly random orientations to promote isotropic mechanical properties. The mechanistic insights into the deformation behaviour of additively manufactured HEAs have broad implications for the development of hierarchical, dual- and multi-phase, nanostructured alloys with exceptional mechanical properties.
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http://dx.doi.org/10.1038/s41586-022-04914-8DOI Listing
August 2022

The effects of repetitive transcranial magnetic stimulation on standing balance and walking in older adults with age-related neurological disorders: a systematic review and meta-analysis.

J Gerontol A Biol Sci Med Sci 2022 Aug 3. Epub 2022 Aug 3.

Hebrew SeniorLife Hinda and Arthur Marcus Institute for Aging Research, Harvard Medical School, Boston, MA, United States.

Background: Considerable evidence showed that repetitive transcranial magnetic stimulation (rTMS) can improve standing balance and walking performance in older adults with age-related neurological disorders. We here thus completed a systematic review and meta-analysis to quantitatively examine such benefits of rTMS.

Methods: A search strategy based on the PICOS principle was used to obtain the literature in four databases. The screening and assessments of quality and risk of bias in the included studies were independently completed by two researchers. Outcomes included scales related to standing balance, Timed Up and Go (TUG) time, and walking speed/time/distance.

Results: Twenty-three studies consisting of 532 participants were included, and the meta-analysis was completed on 21 of these studies. The study quality was good. Compared to control, rTMS induced both short-term (≤3 days after last intervention session) and long-term (≥1 month following last intervention session) significant improvements in balance scales (e.g., Berg Balance Scale), TUG time, and walking speed/time/distance (short-term: standardized mean difference [SMD]=0.26~0.34, 95% confidence interval [CI]=0.05~0.62; long-term: SMD=0.40~0.44, 95% CI=0.04~0.79) for both PD and stroke cohorts. Subgroup analyses suggested that greater than nine sessions of high-frequency rTMS targeting primary motor cortex with greater than 3000 pulses per week can maximize such benefits. Only few mild-to-moderate adverse events/side effects were reported, which were similar between rTMS and control group.

Conclusion: The results suggest that rTMS holds promise to improve balance and walking performance in older adults with age-related neurological disorders. Future studies with more rigorous design are needed to confirm the observations in this work.
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http://dx.doi.org/10.1093/gerona/glac158DOI Listing
August 2022

Correction: Chicken jejunal microbiota improves growth performance by mitigating intestinal inflammation.

Microbiome 2022 Aug 2;10(1):116. Epub 2022 Aug 2.

Department of Basic Veterinary Medicine, College of Animal Science and Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.

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http://dx.doi.org/10.1186/s40168-022-01330-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344750PMC
August 2022

Immune Escape Adaptive Mutations in Hemagglutinin Are Responsible for the Antigenic Drift of Eurasian Avian-Like H1N1 Swine Influenza Viruses.

J Virol 2022 Aug 2:e0097122. Epub 2022 Aug 2.

State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institutegrid.38587.31, Chinese Academy of Agricultural Sciences, Harbin, China.

The continuous antigenic variation of influenza A viruses remains a major hurdle for vaccine selection; however, the molecular determinants and mechanisms of antigenic change remain largely unknown. In this study, two escape mutants were generated by serial passages of the Eurasian avian-like H1N1 swine influenza virus (EA H1N1 SIV) A/swine/Henan/11/2005 (HeN11) in the presence of two neutralizing monoclonal antibodies (mAbs) against the hemagglutinin (HA) protein, which were designated HeN11-2B6-P5 and HeN11-4C7-P8, respectively. The HeN11-2B6-P5 mutant simultaneously harbored the N190D and I230M substitutions in HA, whereas HeN11-4C7-P8 harbored the M269R substitution in HA (H3 numbering). The effects of each of these substitutions on viral antigenicity were determined by measuring the neutralization and hemagglutination inhibition (HI) titers with mAbs and polyclonal sera raised against the representative viruses. The results indicate that residues 190 and 269 are key determinants of viral antigenic variation. In particular, the N190D mutation had the greatest antigenic impact, as determined by the HI assay. Further studies showed that both HeN11-2B6-P5 and HeN11-4C7-P8 maintained the receptor-binding specificity of the parent virus, although the single mutation N190D decreased the binding affinity for the human-type receptor. The replicative ability of HeN11-2B6-P5 was increased, whereas that of HeN11-4C7-P8 was decreased. These findings extend our understanding of the antigenic evolution of influenza viruses under immune pressure and provide insights into the functional effects of amino acid substitutions near the receptor-binding site and the interplay among receptor binding, viral replication, and antigenic drift. The antigenic changes that occur continually in the evolution of influenza A viruses remain a great challenge for the effective control of disease outbreaks. Here, we identified three amino acid substitutions (at positions 190, 230, and 269) in the HA of EA H1N1 SIVs that determine viral antigenicity and result in escape from neutralizing monoclonal antibodies. All three of these substitutions have emerged in nature. Of note, residues 190 and 230 have synergistic effects on receptor binding and antigenicity. Our findings provide a better understanding of the functional effects of amino acid substitutions in HA and their consequences for the antigenic drift of influenza viruses.
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http://dx.doi.org/10.1128/jvi.00971-22DOI Listing
August 2022

Quantification of SHR0302 in human plasma by UPLC-MS/MS and application to a pharmacokinetic study.

Biomed Chromatogr 2022 Aug 2:e5474. Epub 2022 Aug 2.

Department of Pharmacy, Xijing Hospital of the Fourth Military Medical University, Xi'an, China.

SHR0302, as a novel Janus kinase (JAK) inhibitor 1, is used for treatment of rheumatoid arthritis (RA) in humans. A novel and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed and validated for determining the concentration of SHR0302 in human plasma. A precipitation deproteinization method was used for plasma pretreatment with methanol. Detection was carried out on an Agilent 1,260 UPLC coupled with a Triple Quad 4000 mass spectrometer operated in positive multiple reaction monitoring mode, and the analytes were separated on a Synergi Polar-RP C (50 × 2.0 mm, 4 μm, Phenomenex) analytical column with gradient elution of 0.1% formic acid, and 2 mmol/l ammonium acetate in water and 0.1% formic acid and 2 mmol/l ammonium acetate in methanol, The selected ion transitions were m/z 415.2 → 258.2 and m/z 398.2 → 258.2 for SHR0302 and SHR143181 (internal standard), respectively. A full validation, including selectivity, linearity, carryover, precision, accuracy, recovery, matrix effect, dilution integrity and stability, was carried out in human plasma. It was successfully applied to a pharmacokinetic study in Chinese healthy subjects after oral administration of SHR0302 tablet.
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http://dx.doi.org/10.1002/bmc.5474DOI Listing
August 2022

Developing and evaluating an educational web-based tool for health professions education: the Flipped Classroom Navigator.

BMC Med Educ 2022 Aug 1;22(1):594. Epub 2022 Aug 1.

Centre for Medical and Health Sciences Education, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.

Background: Flipped classroom pedagogy is a blended learning approach applied in undergraduate health professions education. However, teachers and students may require training to effectively engage in flipped classroom pedagogy. Thus, this study aimed to design, develop, and evaluate a web-based tool for fostering flipped classroom pedagogy in undergraduate health professions education.

Methods: This is an educational design-based research with a descriptive evaluation component which was conducted in two steps: (i) design & development and (ii) evaluation of an educational website. An expert panel was formed to evaluate the website by using a website evaluation questionnaire (WEQ). Descriptive statistics were employed to calculate the experts' agreement level.

Results: An innovative website design was used to provide access to a range of digital devices. The development process occurred concurrently in two steps: (i) website development and (ii) learning content development. The educational website was branded as the Flipped Classroom Navigator (FCN). Based on WEQ scores, the FCN obtained a good level of agreement (≥ 80%) for its' ease of use, hyperlinks, structure, relevance, comprehension, completeness, and layout.

Conclusions: The FCN is an effective method for providing training to promote flipped classroom pedagogy in health professions education. The FCN achieved good evaluation scores and comments from experts. However, it is also necessary to obtain acceptance from the end-users, which could be the focus of future research. Nonetheless, the expert panel pinpointed areas for further development before introducing the FCN to end-users.
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http://dx.doi.org/10.1186/s12909-022-03647-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344763PMC
August 2022

Association between methylation and hypertension in Chinese adults.

Postgrad Med J 2022 Aug 1. Epub 2022 Aug 1.

Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases of Soochow University, Suzhou, Jiangsu, China

Background: Corin, a physical activator of atrial natriuretic peptide, has been associated with hypertension with unclear mechanisms. Here, we aimed to examine whether gene methylation was involved in the underlying molecular mechanisms.

Methods: DNA methylation levels of were measured by target bisulfite sequencing using genomic DNA isolated from peripheral blood mononuclear cells in 2498 participants in the Gusu cohort (discovery sample) and 1771 independent participants (replication sample). We constructed a mediation model with DNA methylation as the predictor, serum corin as the mediator, and hypertension as the outcome, adjusting for covariates. Multiple testing was controlled by false discovery rate (FDR) approach.

Results: Of the 9 CpGs assayed, hypermethylation at all CpGs were significantly associated with a lower level of blood pressure in the discovery sample and eight associations were also significant in the replication sample (all FDR-adjusted p<0.05). Serum corin mediated approximately 3.07% (p=0.004), 6.25% (p=0.002) and 10.11% (p=0.034) of the associations of hypermethylation at one CpG (Chr4:47840096) with systolic and diastolic blood pressure, and hypertension, respectively. All these mediations passed the causal inference test.

Conclusions: These results suggest that hypermethylation in the gene is associated with a lower odds of prevalent hypertension and may be involved in the role of corin in blood pressure regulation.
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http://dx.doi.org/10.1136/pmj-2022-141802DOI Listing
August 2022

Morphological changes in the digestive tract of the Chinese soft-shelled turtle () during embryonic development.

J Histotechnol 2022 Aug 1:1-11. Epub 2022 Aug 1.

College of Agriculture and Bioengineering, Heze University, Heze, Shandong, China.

The digestive tract development of the embryo is described through the observation of the embryonic morphology on hematoxylin and eosin stained tissue sections. During the first 9 days of embryonic development, the anterior intestine of the embryo divides into the oral cavity, pharyngeal cavity, esophagus, stomach, and small intestine, while the caudal intestine differentiates into the cloaca, the anterior and caudal tubes of the large intestine. Between days 10-24, the wall of the digestive tract forms a two-layer structure consisting of mucosa and submucosa. The endoderm evolves into epithelial tissue in each part of the digestive tract, the mesoderm goes from a dense cluster of cells to looser mesenchymal tissue then divides into loose connective tissue, mesothelium, and muscle tissue. There is no clear temporal boundary between development of mesenchymal tissue and the early loose connective tissue, which is a gradual process.
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http://dx.doi.org/10.1080/01478885.2022.2105490DOI Listing
August 2022

A review of recent progress in improving the bioavailability of nutraceutical-loaded emulsions after oral intake.

Compr Rev Food Sci Food Saf 2022 Aug 1. Epub 2022 Aug 1.

State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China.

Increasing awareness of the health benefits of specific constituents in fruits, vegetables, cereals, and other whole foods has sparked a broader interest in the potential health benefits of nutraceuticals. Many nutraceuticals are hydrophobic substances, which means they must be encapsulated in colloidal delivery systems. Oil-in-water emulsions are one of the most widely used delivery systems for improving the bioavailability and bioactivity of these nutraceuticals. The composition and structure of emulsions can be designed to improve the water dispersibility, physicochemical stability, and bioavailability of the encapsulated nutraceuticals. The nature of the emulsion used influences the interfacial area and properties of the nutraceutical-loaded oil droplets in the gastrointestinal tract, which influences their digestion, as well as the bioaccessibility, metabolism, and absorption of the nutraceuticals. In this article, we review recent in vitro and in vivo studies on the utilization of emulsions to improve the bioavailability of nutraceuticals. The findings from this review should facilitate the design of more efficacious nutraceutical-loaded emulsions with increased bioactivity.
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http://dx.doi.org/10.1111/1541-4337.13017DOI Listing
August 2022

Comparison of Outcomes of Haploidentical Peripheral Blood Stem Cell Transplantation Supported by Third-Party Cord Blood Versus Human Leukocyte Antigen-Matched Sibling Peripheral Blood Stem Cell Transplantation in Hematologic Malignancy Patients.

Front Oncol 2022 14;12:922120. Epub 2022 Jul 14.

Department of Hematology, Xiangya Hospital, Central South University, Changsha, China.

Recent studies have shown that haploidentical hematopoietic stem cell transplantation supported by third-party cord blood (haplo-cord-HSCT) results in rapid hematopoietic recovery, low incidences of graft-versus-host disease (GVHD), and relapse of hematologic malignancies. However, few reports on haploidentical peripheral blood stem cell transplantation supported by third-party cord blood (haplo-cord-PBSCT) have been published. To evaluate the outcomes of patients who underwent haplo-cord-PBSCT or human leukocyte antigen (HLA)-matched sibling donor peripheral blood stem cell transplantation (MSD-PBSCT), we retrospectively reviewed the clinical data of patients with hematologic malignancies who underwent haplo-cord-PBSCT (n = 93) or MSD-PBSCT (n = 72) in our hospital from March 2017 to December 2020. In the haplo-cord-PBSCT and MSD-PBSCT groups, the median time for neutrophil and platelet engraftment was 13 vs. 12 days ( = 0.07) and 16 vs. 13 days ( = 0.06), respectively. The 30-day cumulative incidences of neutrophil engraftment were 100.0% and 98.6% ( = 0.12). The 100-day cumulative incidences of platelet engraftment were 96.8% and 98.6% ( = 0.01). The 100-day cumulative incidences of grade II-IV and grade III-IV acute GVHD were 29.1% vs. 23.6% ( = 0.42) and 9.7% vs. 4.2% ( = 0.18). The cumulative incidences of total and moderate/severe chronic GVHD at 1 year were 26.5% vs. 17.4% and 8.1% vs. 4.5%, respectively, and at 3 years were 34.7% vs. 34.3% ( = 0.60) and 13.6% vs. 10.6% ( = 0.49), respectively. The cumulative incidences of relapse at 1 year were 9.3% and 7.2% and at 3 years were 17.0% and 17.0% ( = 0.98). Non-relapse mortality (NRM) at 1 year was 14.6% and 8.6% and at 3 years was 17.4% and 8.6% ( = 0.13) in two groups. The probabilities of overall survival (OS), disease-free survival (DFS), and GVHD-free/relapse-free survival (GRFS) at 1 year were 81.7% vs. 88.6%, 76.1% vs. 84.2%, and 71.7% vs. 79.7%, respectively, and at 3 years were 78.7% vs. 79.0%, 65.6% vs. 74.4%, and 55.5% vs. 63.6%, respectively, in the corresponding group, > 0.05. In conclusion, for patients with acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) and acute lymphoid leukemia (ALL), haplo-cord-PBSCT results in similar outcomes compared with MSD-PBSCT, and it may be a valid alternative transplantation method.
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http://dx.doi.org/10.3389/fonc.2022.922120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331161PMC
July 2022

The Role of The Tumor Microbiome in Tumor Development and Its Treatment.

Front Immunol 2022 15;13:935846. Epub 2022 Jul 15.

Department of Hematology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.

Commensal bacteria and other microorganisms that reside in the human body are closely associated with the development and treatment of cancers. Recently, tumor microbiome (TM) has been identified in a variety of cancers such as pancreatic, lung, and breast cancers. TM has different compositions in different tumors and has different effects on tumors. TM plays an important role in the formation of the tumor microenvironment, regulation of local immunity, and modification of tumor cell biology, and directly affects the efficacy of drug treatment for tumors. TM is expected to be a biomarker for tumors, and engineered tumor-targeting bacteria and anti-cancer microbial agents (GEN-001) have an important role in the treatment of tumors. This paper reviews the relevant studies on TM in recent years and describes its distribution in different tumors, its correlation with clinical features, its effect on local immunity, and the research directions of TM in tumor treatment.
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http://dx.doi.org/10.3389/fimmu.2022.935846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334697PMC
August 2022

Construction of Women's All-Around Speed Skating Event Performance Prediction Model and Competition Strategy Analysis Based on Machine Learning Algorithms.

Front Psychol 2022 12;13:915108. Epub 2022 Jul 12.

Harvard Medical School, Hebrew SeniorLife Hinda and Arthur Marcus Institute for Aging Research, Boston, MA, United States.

Introduction: Accurately predicting the competitive performance of elite athletes is an essential prerequisite for formulating competitive strategies. Women's all-around speed skating event consists of four individual subevents, and the competition system is complex and challenging to make accurate predictions on their performance.

Objective: The present study aims to explore the feasibility and effectiveness of machine learning algorithms for predicting the performance of women's all-around speed skating event and provide effective training and competition strategies.

Methods: The data, consisting of 16 seasons of world-class women's all-around speed skating competition results, used in the present study came from the International Skating Union (ISU). According to the competition rules, distinct features are filtered using lasso regression, and a 5,000 m race model and a medal model are built using a fivefold cross-validation method.

Results: The results showed that the support vector machine model was the most stable among the 5,000 m race and the medal models, with the highest AUC (0.86, 0.81, respectively). Furthermore, 3,000 m points are the main characteristic factors that decide whether an athlete can qualify for the final. The 11th lap of the 5,000 m, the second lap of the 500 m, and the fourth lap of the 1,500 m are the main characteristic factors that affect the athlete's ability to win medals.

Conclusion: Compared with logistic regression, random forest, K-nearest neighbor, naive Bayes, neural network, support vector machine is a more viable algorithm to establish the performance prediction model of women's all-around speed skating event; excellent performance in the 3,000 m event can facilitate athletes to advance to the final, and athletes with outstanding performance in the 500 m event are more likely competitive for medals.
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http://dx.doi.org/10.3389/fpsyg.2022.915108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326501PMC
July 2022

Does It Matter to Establish a Strategic Partnership for COVID-19 Prevention and Control? The Perspective of Multiple Distances in Emerging Economies.

Front Public Health 2022 14;10:894816. Epub 2022 Jul 14.

School of Economics and Management, Beijing University of Posts and Telecommunications, Beijing, China.

The rapid spread of the COVID-19 pandemic in early 2020 has impacted the politics, economy and society of countries around the world. The public health diplomacy system through which developed countries in Europe and America used to provide vertical one-way assistance to developing countries faces huge challenges. How emerging economies can cooperate to fight the pandemic on the basis of mutual trust and mutual benefit has become an urgent issue. In this paper, we examine the impact of political mutual trust on the effectiveness of pandemic prevention and control from the perspective of establishing strategic partnerships between emerging economies. Furthermore, taking into account the huge differences between emerging economies, this paper explores institutional distance, cultural distance, and geographical distance-the adjustment effect of the control effect. Studies have shown that the improvement of political mutual trust is conducive to the formation of a community of shared futures between countries and has a positive effect on curbing the spread of the pandemic. The increase of the three-dimensional distance of institutions, culture, and geography will weaken the effect of establishing strategic partners for pandemic prevention and control. This paper explores a new model of horizontal international cooperation among emerging economies, and provides a reference for emerging economies to deal with common globalization issues in the future.
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http://dx.doi.org/10.3389/fpubh.2022.894816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329684PMC
July 2022

Is the METS-IR Index a Potential New Biomarker for Kidney Stone Development?

Front Endocrinol (Lausanne) 2022 14;13:914812. Epub 2022 Jul 14.

Department of Urology, the First Affiliated Hospital of Anhui Medical University, Hefei City, China.

Objective: The purpose of this study was to examine whether the METS-IR index is associated with kidney stones in American adults.

Method: Participants from the National Health and Nutrition Examination Survey (NHANES) database from 2007-2018 were selected for logistic regression analysis, subgroup analyses, and the calculation of dose-response curves to assess the association between the METS-IR index and the incidence of kidney stones.

Result: This study enrolled 30,612 adults aged >20 years, 2901 of whom self-reported having had kidney stones in the past. And, after controlling for potential confounders, each unit increase in the METS-IR index was linked with a 1.23 percent rise in kidney stone incidence (OR= 1.0123, 95% CI: 1.0092 - 1.0155), with stratified analysis indicating that this was true in all subgroups. Between all groups, an elevated METS-IR index was related to kidney stone formation, and the dose-response curve revealed a positive non-linear connection between METS-IR index and kidney stone risk, with a threshold effect analysis revealing an inflection point value of 50.8314.

Conclusion: Higher METS-IR index is associated with the occurrence of kidney stones,and while no causative association can be shown, this is cause for concern.
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http://dx.doi.org/10.3389/fendo.2022.914812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329808PMC
July 2022

Aquaporins: Important players in the cardiovascular pathophysiology.

Pharmacol Res 2022 Jul 26;183:106363. Epub 2022 Jul 26.

Gansu University of traditional Chinese Medicine, LanZhou, China; Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and the Prevention and Treatment with Traditional Chinese Medicine Research in Gansu Colleges and Universities Gansu University of Chinese Medicine, Lanzhou, China; Key Laboratory of Dunhuang Medicine and Transformation at Provincial and Ministerial Level, Lanzhou, China. Electronic address:

Aquaporin is a membrane channel protein widely expressed in body tissues, which can control the input and output of water in cells. AQPs are differentially expressed in different cardiovascular tissues and participate in water transmembrane transport, cell migration, metabolism, inflammatory response, etc. The aberrant expression of AQPs highly correlates with the onset of ischemic heart disease, myocardial ischemia-reperfusion injury, heart failure, etc. Despite much attention to the regulatory role of AQPs in the cardiovascular system, the translation of AQPs into clinical application still faces many challenges, including clarification of the localization of AQPs in the cardiovascular system and mechanisms mediating cardiovascular pathophysiology, as well as the development of cardiovascular-specific AQPs modulators.Therefore, in this study, we comprehensively reviewed the critical roles of AQP family proteins in maintaining cardiovascular homeostasis and described the underlying mechanisms by which AQPs mediated the outcomes of cardiovascular diseases. Meanwhile, AQPs serve as important therapeutic targets, which provide a wide range of opportunities to investigate the mechanisms of cardiovascular diseases and the treatment of those diseases.
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http://dx.doi.org/10.1016/j.phrs.2022.106363DOI Listing
July 2022

Construction of a I-Labeled Specific Antibody for the Noninvasive Detection of Mesothelin-Overexpressing Tumors.

Mol Pharm 2022 Jul 29. Epub 2022 Jul 29.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital and Institute, Beijing 100142, China.

Mesothelin (MSLN) is a molecular biomarker of many types of solid tumors, such as mesothelioma, pancreatic cancer, and colon cancer. Owing to the significant difference in expression between cancer cells and normal cells, mesothelin has been widely used as a key target in cancer immunotherapy. In this study, we used iodine isotope (I)-labeled mesothelin antibodies to noninvasively detect MSLN expression in mice with LS174T colon cancer. The I-labeled MSLN antibody showed a high radiochemical purity (RCP, >99%) and specific activity (20.8-67.8 GBq/μmol) after purification and was stable in 5% HSA and PBS (>95% RCP at 8 days). Western blot analysis indicated that the LS174T cells showed a higher MSLN protein level than the HepG2 cells. The half maximal effective concentration (EC) values of the MSLN antibody and I-anti-MSLN were 34.77 ± 3.72 ng/mL and 32.60 ± 2.52 ng/mL ( = 0.63), respectively. The dissociation constant of I-anti-MSLN binding to MSLN protein was 16.0 nM. The radiotracer showed a significantly higher uptake in LS174T cells than in HepG2 tumor cells (1.56 ± 0.09 vs 0.81 ± 0.03, = 0.0016) 2 days postinjection. The LS174T mouse models showed extremely low organ uptake and high tumor uptake 96 h after the injection of I-anti-MSLN, and the T/M values were much higher than those of the other imaging groups (10.56 ± 1.20 for I-anti-MSLN in LS174T mice vs 3.27 ± 0.20 for I-anti-MSLN in HepG2 mice vs 3.53 ± 0.2 for I-IgG in LS174T mice). The immunochemical histology results showed that LS174T tumors were strongly positive (+++) for MSLN, while those in the HepG2 group showed slight expression (+). The dosimetry estimation study showed that the effective dose of I-anti-MSLN was 0.185 mSv/MBq, which is within the range of acceptable doses for further nuclear medicine translational research. Taken together, these results suggest that this radiotracer has the potential for detecting mesothelin-overexpressing tumors.
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http://dx.doi.org/10.1021/acs.molpharmaceut.2c00342DOI Listing
July 2022

Bidirectional Interface Protection of a Concentrated Electrolyte, Enabling High-Voltage and Long-Life Aqueous Zn Hybrid-Ion Batteries.

ACS Appl Mater Interfaces 2022 Aug 28;14(31):35864-35872. Epub 2022 Jul 28.

School of Advanced Materials, Peking University Shenzhen Graduate School, Shenzhen 518055, China.

Prussian blue analogues (PBAs) as a promising high-voltage cathode material for aqueous zinc-ion batteries (ZIBs) are usually subjected to an ephemeral lifespan and low Coulombic efficiency due to the irreversible phase change and high Zn insertion potential. Besides, Zn dendrites, H evolution reaction, and corrosion derived from a Zn anode interface remain huge challenges. Given this, a highly stable zinc hexacyanoferrate (KZnHCF) cathode together with a mixed concentrated electrolyte is prepared to realize a high-voltage and long-life aqueous ZIB, in which the mixed concentrated electrolyte consisting of 30 m KFSI + 1 m Zn(CFSO) possesses a unique Zn solvation sheath (Zn(CFSO)(FSI)(HO)) that can not only stabilize the cathode interface and improve the Coulombic efficiency but also fundamentally solve the Zn anode interface issues. As a result, the aqueous KZnHCF/Zn battery achieves an ultralong life over 3000 cycles without any capacity decay even under a high discharge voltage of 1.78 V (vs Zn/Zn). Such extraordinary performance represents significant progress in aqueous PBA-based ZIBs. This work shares guidance to improve the performance of aqueous ZIBs through optimizing the electrolyte in tuning the stable operation of the cathode and the zinc anode.
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http://dx.doi.org/10.1021/acsami.2c09993DOI Listing
August 2022

miR-4443/MMP2 suppresses the migration and invasion of trophoblasts through the HB-EGF/EGFR pathway in preeclampsia.

Cell Cycle 2022 Jul 28:1-16. Epub 2022 Jul 28.

International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Preeclampsia (PE) is a pregnancy-associated disease that may cause maternal and fetal morbidity and mortality. The dysregulation of microRNAs (miRNAs) and their potential functions has been an important direction for elucidating the mechanism of preeclampsia in recent years. The present study investigated whether miR-4443 was significantly increased in the placentas of severe preeclamptic patients, and the upregulation of miR-4443 inhibited the migration and invasion of HTR-8/SVneo cells according to transwell assays. Matrix metallopeptidase 2 (MMP2), which is involved in the degradation of extracellular matrix (ECM) components and harbors a miR-4443-binding site within its 3'-UTR as confirmed by a luciferase reporter assay, was identified to be directly inhibited by miR-4443. Moreover, siRNA targeting MMP2 imitated the effects of overexpressed miR-4443 on HTR-8/SVneo cell invasion and migration, whereas rescue experiments showed that MMP2 reversed this inhibitory function of miR-4443. Heparin-binding EGF-like growth factor (HB-EGF), as the downstream gene of MMP2, plays an important role in trophoblast invasion, and we confirmed that the expression of HB-EGF/EGFR pathway-related biomolecules was consistent with MMP2 influenced by upregulating and downregulating miR-4443 and that activated EGFR further transmitted intracellular downstream signaling via the MAPK pathway according to western blot assay. In conclusion, we demonstrated that miR-4443 suppresses the migration and invasion of trophoblasts, and its inhibitory effects are at least partially mediated by the suppression of MMP2. This inhibition might further affect the progression of preeclampsia through the HB-EGF/EGFR pathway, thus providing a new clue on the role of miR-4443 in the pathogenesis of preeclampsia.
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http://dx.doi.org/10.1080/15384101.2022.2103897DOI Listing
July 2022
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