Publications by authors named "Xin Yu"

1,713 Publications

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Dominant Negative Mutants of Human Immunodeficiency Virus Type 1 Viral Infectivity Factor (Vif) Disrupt Core-Binding Factor Beta-Vif Interaction.

J Virol 2022 Aug 11:e0055522. Epub 2022 Aug 11.

National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin Universitygrid.64924.3d, Changchun, Jilin Province, China.

Apolipoprotein B mRNA-editing catalytic polypeptide-like 3 family members (APOBEC3s) are host restriction factors that inhibit viral replication. Viral infectivity factor (Vif), a human immunodeficiency virus type 1 (HIV-1) accessory protein, mediates the degradation of APOBEC3s by forming the Vif-E3 complex, in which core-binding factor beta (CBFβ) is an essential molecular chaperone. Here, we screened nonfunctional Vif mutants with high affinity for CBFβ to inhibit HIV-1 in a dominant negative manner. We applied the yeast surface display technology to express Vif random mutant libraries, and mutants showing high CBFβ affinity were screened using flow cytometry. Most of the screened Vif mutants containing random mutations of different frequencies were able to rescue APOBEC3G (A3G). In the subsequent screening, three of the mutants restricted HIV-1, recovered G-to-A hypermutation, and rescued APOBEC3s. Among them, Vif-6M showed a cross-protection effect toward APOBEC3C, APOBEC3F, and African green monkey A3G. Stable expression of Vif-6M in T lymphocytes inhibited the viral replication in newly HIV-1-infected cells and the chronically infected cell line H9/HXB2. Furthermore, the expression of Vif-6M provided a survival advantage to T lymphocytes infected with HIV-1. These results suggest that dominant negative Vif mutants acting on the Vif-CBFβ target potently restrict HIV-1. Antiviral therapy cannot eliminate HIV and exhibits disadvantages such as drug resistance and toxicity. Therefore, novel strategies for inhibiting viral replication in patients with HIV are urgently needed. APOBEC3s in host cells are able to inhibit viral replication but are antagonized by HIV-1 Vif-mediated degradation. Therefore, we screened nonfunctional Vif mutants with high affinity for CBFβ to compete with the wild-type Vif (wtVif) as a potential strategy to assist with HIV-1 treatment. Most screened mutants rescued the expression of A3G in the presence of wtVif, especially Vif-6M, which could protect various APOBEC3s and improve the incorporation of A3G into HIV-1 particles. Transduction of Vif-6M into T lymphocytes inhibited the replication of the newly infected virus and the chronically infected virus. These data suggest that Vif mutants targeting the Vif-CBFβ interaction may be promising in the development of a new AIDS therapeutic strategy.
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http://dx.doi.org/10.1128/jvi.00555-22DOI Listing
August 2022

Clinical characteristics of 310 SARS-CoV-2 Omicron variant patients and comparison with Delta and Beta variant patients in China.

Virol Sin 2022 Aug 7. Epub 2022 Aug 7.

Department of Critical Care Medicine, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, China. Electronic address:

Although the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has spread, data on the clinical characteristics of infected patients are limited. In this study, the demographic, clinical characteristics, and laboratory data of 310 SARS-CoV-2 Omicron variant patients treated at Haihe Hospital of Tianjin were collected and analyzed. Information on these patients was compared to 96 patients with the Delta variant of concern (VOC) and 326 patients with the Beta VOC during the previous coronavirus disease 2019 (COVID-19) outbreak in Harbin. Of the 310 patients infected with the Omicron variant, the median age was 35 years. Most patients were clinically classified as mild (57.74%), and the most common symptoms were cough (48.71%), fever (39.35%), and sore throat (38.26%). The results for different vaccination groups in the Omicron group showed that the median of "SARS-CoV-2 specific IgG" after 2 or 3 doses of vaccination was higher than the unvaccinated group (all Ps < 0.05). Older age was associated with a higher proportion of moderate cases and lower asymptomatic and mild cases based on clinical classifications. Compared to the Delta and Beta groups, the median age of the Omicron group was younger. The total number of asymptomatic patients and mild patients in the Omicron virus group was higher than the Delta and Beta groups (60.97% vs. 54.17% vs. 47.55%). This study presented the clinical characteristics of the first group of patients infected with the Omicron variant in Tianjin, China, and compared their clinical features with patients infected by the Delta and Beta variants, which would increase our understanding of the characteristics of SARS-CoV-2 Omicron variant.
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http://dx.doi.org/10.1016/j.virs.2022.07.014DOI Listing
August 2022

Virioplankton assemblages from challenger deep, the deepest place in the oceans.

iScience 2022 Aug 27;25(8):104680. Epub 2022 Jun 27.

College of Marine Life Sciences, Institute of Evolution and Marine Biodiversity, Frontiers Science Center for Deep Ocean Multispheres and Earth System, Key Lab of Polar Oceanography and Global Ocean Change, Ocean University of China, Qingdao 266003, China.

Hadal ocean biosphere, that is, the deepest part of the world's oceans, harbors a unique microbial community, suggesting a potential uncovered co-occurring virioplankton assemblage. Herein, we reveal the unique virioplankton assemblages of the Challenger Deep, comprising 95,813 non-redundant viral contigs from the surface to the hadal zone. Almost all of the dominant viral contigs in the hadal zone were unclassified, potentially related to Alteromonadales and Oceanospirillales. 2,586 viral auxiliary metabolic genes from 132 different KEGG orthologous groups were mainly related to the carbon, nitrogen, sulfur, and arsenic metabolism. Lysogenic viral production and integrase genes were augmented in the hadal zone, suggesting the prevalence of viral lysogenic life strategy. Abundant rve genes in the hadal zone, which function as transposase in the caudoviruses, further suggest the prevalence of viral-mediated horizontal gene transfer. This study provides fundamental insights into the virioplankton assemblages of the hadal zone, reinforcing the necessity of incorporating virioplankton into the hadal biogeochemical cycles.
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http://dx.doi.org/10.1016/j.isci.2022.104680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356048PMC
August 2022

Oncolytic Impediment/Promotion Balance Disruption by Sonosensitizer-Free Nanoplatforms Unfreezes Autophagy-Induced Resistance to Sonocatalytic Therapy.

ACS Appl Mater Interfaces 2022 Aug 8. Epub 2022 Aug 8.

Central Laboratory, Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301 Yan-chang-zhong Road, Shanghai 200072, P. R. China.

Autophagy as a double-edged sword features an oncolytic impediment/promotion balance, which manipulates tumor progression. From this perspective, a sonosensitizer-free targeting oncolytic nanoplatform (SFTON) consisting of chloroquine (CQ) and porphyrin-structured metal centers (PMCS) was engineered to break this balance for enhancing antitumor activity. Porphyrin structure retention in a ZIF-8-derived hydrophobic carbon skeleton retained high stability and high sonocatalytic activity, and the hydrophobic carbon skeleton capable of adsorbing air provided cavitation nuclei for further elevating sonocatalytic activity. More significantly, the encapsulated CQ as the autophagy inhibitor reprogrammed autophagy, terminated the autophagy-induced self-protection or self-detoxification, and unfroze the resistances to reactive oxygen species (ROS) therapy associated with ROS accumulation and ROS activity. Systematic experiments reveal the action principles and validate that the induced apoptosis and blockaded autophagosome escalation into the autolysosome were two activated pathways to magnify the antitumor sonocatalytic therapy. Contributed by these actions, the SFTON-unlocked oncolytic impediment/promotion balance disruption strategy acquired considerable antitumor outcomes in vivo and in vitro against liver tumor progression, especially after combining with AS1411-mediated active targeting. This impediment/promotion balance disruption enabled by the SFTON can serve as a general method to elevate ROS-based antitumor activity.
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http://dx.doi.org/10.1021/acsami.2c09443DOI Listing
August 2022

Instability Mechanism of Osimertinib in Plasma and a Solving Strategy in the Pharmacokinetics Study.

Front Pharmacol 2022 22;13:928983. Epub 2022 Jul 22.

The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing, China.

Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and a star medication used to treat non-small-cell lung carcinomas (NSCLCs). It has caused broad public concern that osimertinib has relatively low stability in plasma. We explored why osimertinib and its primary metabolites AZ-5104 and AZ-7550 are unstable in rat plasma. Our results suggested that it is the main reason inducing their unstable phenomenon that the Michael addition reaction was putatively produced between the Michael acceptor of osimertinib and the cysteine in the plasma matrix. Consequently, we identified a method to stabilize osimertinib and its metabolite contents in plasma. The assay was observed to enhance the stability of osimertinib, AZ-5104, and AZ-7550 significantly. The validated method was subsequently applied to perform the pharmacokinetic study for osimertinib in rats with the newly established, elegant, and optimized ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) strategy. The assay was assessed for accuracy, precision, matrix effects, recovery, and stability. This study can help understand the pharmacological effects of osimertinib and promote a solution for the similar problem of other Michael acceptor-contained third-generation EGFR-TKI.
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http://dx.doi.org/10.3389/fphar.2022.928983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354582PMC
July 2022

The Structure and Function of Microbial Community in Rhizospheric Soil of American Ginseng (Panax quinquefolius L.) Changed with Planting Years.

Curr Microbiol 2022 Aug 8;79(9):281. Epub 2022 Aug 8.

School of Life Sciences, Ludong University, 186 Hongqi Road, Zhifu District, Yantai, 264025, Shandong, China.

The changes of microbial communities of rhizospheric soil in different ages are speculated to cause soil-borne diseases and replanting problem in American ginseng (Panax quinquefolius L.) cultivation. This study analyzed the physicochemical properties and microbial communities of rhizospheric soil during the planting of American ginseng in the Wendeng area of Weihai, China. The water content and organic matter content of American ginseng rhizospheric soil decreased year by year. A decline in the diversity of bacteria and fungi was observed in the rhizospheric soils planting American ginseng compared with the traditional crop wheat in the control group. During the later planting stage, the abundances of Proteobacteria, Actinobacteria, and Basidiomycota were lower, whereas that of Acidobacteria, Firmicutes, and Mucoromycota were higher. Through the correlation analysis between environmental factors and microbial community, it was found that the content of soil phosphorus was significantly positively correlated with the root rot pathogen Fusarium. The results of functional prediction showed that the decrease of secondary metabolite synthesis of rhizospheric soil bacteria and the increase of plant pathogenic fungi may be the important reasons for the increase of diseases in the later stage of American ginseng planting. This study revealed the evolution of rhizosphere microbial community and function in the process of American ginseng planting, which is valuable for planting management.
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http://dx.doi.org/10.1007/s00284-022-02941-2DOI Listing
August 2022

Graphdiyne reinforced multifunctional Cu/Ni bimetallic Phosphides-Graphdiyne hybrid nanostructure as high performance electrocatalyst for water splitting.

J Colloid Interface Sci 2022 Jul 28;628(Pt A):508-518. Epub 2022 Jul 28.

School of Chemistry and Chemical Engineering, Beijing Institute of Technology, No. 5, South Street, Zhongguancun, Haidian District, Beijing 100081, PR China. Electronic address:

Obtaining of non-noble metal catalyst with bifunctional effect for both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in water splitting is highly desired to get high purity hydrogen. Here in, we design and fabricate Cu/Ni bimetallic phosphides with Graphdiyne (GDY) to form hybrid nanomaterial CuNiPx-GDY on Ni foam for the first time. The synergistical effect between GDY and transition metal phosphides, and the atomic scale heterojunctions between CuP and NiP, effectively accelerate the catalytical process both in HER and OER, resulting in extraordinarily small overpotentials of 178 mV and 110 mV at 10 mA cm for OER and HER in CuNiPx-GDY(1:1) in 1 M KOH, respectively. Density functional theory results show that, compared with pure CuNiPx, the introduced GDY can considerably improve the activity of OER and generate different active sites for OER and HER in CuNiPx-GDY(1:1). Thus CuNiPx-GDY(1:1) exhibits good catalytical performance and stability as catalyst for overall water splitting. This study provides a new sight into the structure and catalytic properties of GDY and transition metal phosphides hybrid nanomaterial, and also offers a new way to obtain advanced materials with remarkable catalytic properties.
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http://dx.doi.org/10.1016/j.jcis.2022.07.150DOI Listing
July 2022

Effectiveness and safety of low-dose interferon alpha-2a treatment in Behçet's Syndrome with refractory vascular or neurological involvement: a case series.

Ther Adv Chronic Dis 2022 26;13:20406223221111285. Epub 2022 Jul 26.

Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dongcheng-qu, Beijing 100730, China.

Objective: The aim of this study was to evaluate the effectiveness and safety of low-dose interferon alpha-2a (IFNα2a) in Behçet's syndrome (BS) patients with refractory vascular/cardiac or neurological involvement.

Methods: In this retrospective cohort study, we consecutively included 25 BS patients with refractory vascular/cardiac ( = 16) or neurological involvement ( = 9) who received IFNα2a treatment in our center between June 2018 and September 2021. The low-dose IFNα2a (3 million IU, every other day) was used as an add-on treatment with the continuation of glucocorticoids (GCs) and immunosuppressants.

Results: In total, 25 patients (20 males, 5 females) with a mean age of 31.92 ± 9.25 years were included. IFNα2a was administered for BS patients with refractory vascular/cardiac involvement ( = 16) and neurological involvement ( = 9). Before the initiation of IFNα2a, patients had insufficient response or intolerance to conventional therapies. After a median follow-up of 23 [interquartile range (IQR), 11-30] months, all patients achieved clinical improvement. The Behçet's disease Current Activity Form (BDCAF) score improved significantly (5 0, median,  < 0.0001). BS Overall Damage Index (BODI) and vasculitis damage index (VDI) remain stable ( > 0.05). Decrease in erythrocyte sedimentation rate [ESR; 24 (IQR, 12-43.5) 5 (IQR, 2.75-10.5) mm/h,  = 0.0001] and C-reactive protein [CRP; 6.64 (IQR, 3.67-19.82) 1.24 (IQR, 0.24-3.12) mg/liter,  < 0.005] was achieved effectively. The median GCs dosage tapered from 26.25 (IQR, 11.88-41.25) to 10.00 (IQR, 7.50-10.63) mg/d,  < 0.0001. Immunosuppressants were also reduced in number ( < 0.005). No serious adverse events were observed during follow-up.

Conclusion: Our study suggests that low-dose IFNα2a, combined with GCs and immunosuppressants, is well-tolerated and effective for BS patients with refractory vascular/cardiac or neurological involvement and has a steroid- and immunosuppressant-sparing effect.
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http://dx.doi.org/10.1177/20406223221111285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9340357PMC
July 2022

Combining Immune-Related Genes For Delineating the Extracellular Matrix and Predicting Hormone Therapy and Neoadjuvant Chemotherapy Benefits In Breast Cancer.

Front Immunol 2022 14;13:888339. Epub 2022 Jul 14.

Department of Oncology, Harbin Medical University, Harbin, China.

Breast cancer (BC) is the most prevalent cancer in women worldwide. A systematic approach to BC treatment, comprising adjuvant and neoadjuvant chemotherapy (NAC), as well as hormone therapy, forms the foundation of the disease's therapeutic strategy. The extracellular matrix (ECM) is a dynamic network that exerts a robust biological effect on the tumor microenvironment (TME), and it is highly regulated by several immunological components, such as chemokines and cytokines. It has been established that the ECM promotes the development of an immunosuppressive TME. Therefore, while analyzing the ECM of BC, immune-related genes must be considered. In this study, we used bioinformatic approaches to identify the most valuable ECM-related immune genes. We used weighted gene co-expression network analysis to identify the immune-related genes that potentially regulate the ECM and then combined them with the original ECM-related gene set for further analysis. Least absolute shrinkage and selection operator (LASSO) regression and SurvivalRandomForest were used to narrow our ECM-related gene list and establish an ECM index (ECMI) to better delineate the ECM signature. We stratified BC patients into ECMI high and low groups and evaluated their clinical, biological, and genomic characteristics. We found that the ECMI is highly correlated with long-term BC survival. In terms of the biological process, this index is positively associated with the cell cycle, DNA damage repair, and homologous recombination but negatively with processes involved in angiogenesis and epithelial-mesenchymal transition. Furthermore, the tumor mutational burden, copy number variation, and DNA methylation levels were found to be related to the ECMI. In the Metabric cohort, we demonstrated that hormone therapy is more effective in patients with a low ECMI. Additionally, differentially expressed genes from the ECM-related gene list were extracted from patients with a pathologic complete response (pCR) to NAC and with residual disease (RD) to construct a neural network model for predicting the chance of achieving pCR individually. Finally, we performed qRT-PCR to validate our findings and demonstrate the important role of the gene OGN in predicting the pCR rate. In conclusion, delineation of the ECM signature with immune-related genes is anticipated to aid in the prediction of the prognosis of patients with BC and the benefits of hormone therapy and NAC in BC patients.
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http://dx.doi.org/10.3389/fimmu.2022.888339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331652PMC
July 2022

Dopamine agonist withdrawal syndrome associated factors: A retrospective chart review.

Clin Park Relat Disord 2022 16;7:100153. Epub 2022 Jul 16.

Neurological Institute, Cleveland Clinic, Center for Neurological Restoration | Cleveland Clinic, 9500 Euclid Ave, Mail Code U2, Cleveland, OH 44195, United States.

Dopamine agonist withdrawal syndrome (DAWS) has been introduced to describe the constellation of symptoms resulting from reduction or suspension of dopamine agonist medications. In patients with Parkinson's disease (PD) the impact of DAWS can be significant in terms of distress and disability. Unfortunately, no standard treatment exists other than reintroduce the dopamine agonist even in the presence of adverse effects. Therefore, identification of vulnerable patients would be beneficial. Previous studies have linked DAWS with impulse control disorder behavior (ICD), higher dopamine agonist doses, and milder motor impairment in PD patients. We conducted a retrospective chart review of PD patients treated with dopamine agonist. A total of 313 charts from January 2011 to December 2013 were reviewed, showing 126 patients who were discontinued from dopamine agonist. Twenty-one patients (16.8 %) fulfilled the diagnostic criteria for DAWS. Factors associated with the occurrence of DAWS were: (1) dose of dopamine agonist ≥150 mg expressed in levodopa equivalents daily dose (LEDD) (p = 0.018), (2) impulse control disorder as an adverse effect to dopamine agonist (p = 0.002), and (3) prior deep brain stimulation (DBS) (p = 0.049). The probability of developing DAWS in the presence of all 3 identified factors was 92 %; presence of 2 factors raised the probability up to 70 %; the presence of one factor increased the probability up to 30 %. In the absence of these 3 factors the probability of developing DAWS was 3 %. Prospective studies are warranted to confirm these findings.
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http://dx.doi.org/10.1016/j.prdoa.2022.100153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9335375PMC
July 2022

Distribution and clinical significance of circulating CD8CD28 regulatory T cells in the peripheral blood of patients with pulmonary tuberculosis.

BMC Pulm Med 2022 Jul 30;22(1):291. Epub 2022 Jul 30.

Department of Clinical Laboratory, The Fifth People's Hospital of Suzhou, 10, Guanqian Road, Suzhou, 215000, Jiangsu, People's Republic of China.

Background: Regulatory T cells (Treg cells) in the peripheral blood of patients with pulmonary tuberculosis (PTB) may be closely related to the progression of PTB. In this study, the distribution characteristics and clinical importance of CD8CD28 Treg cells in patients with tuberculosis were systematically analyzed, and the role and importance of CD8CD28 Treg cells in influencing the immune response and progression of tuberculosis were discussed, which will provide immunological indices and reference values for the clinical diagnosis of tuberculosis.

Methods: Flow cytometry, sputum smears and computed tomography imaging were used to analyze the distribution characteristics of CD8CD28 Treg cells in the peripheral blood of patients with PTB and the correlation between CD8CD28Treg cells and clinical and immune indices.

Results: The percentages of CD4CD25 and CD8CD28 Treg cells in the peripheral blood of patients with PTB were significantly higher than those in the healthy control (HC) group. Further analysis showed that the percentage of CD4CD25Treg cells in the Stage II group was significantly higher than that in the HC group. The percentages of CD4CD25 and CD8CD28 Treg cells increased significantly in patients in the Stage II group. The proportion of CD8CD28 Treg cells was directly proportional to the degree of positivity in sputum smears, while CD4CD25Treg cells did not exhibit this trend. The correlations between the percentage of CD4CD25 and CD8CD28 Treg cells and the percentage of lymphocyte subsets were examined. The percentage of CD8CD28 Treg cells was negatively correlated with the percentage of CD4T cells and positively correlated with the CD8T cell percentage in the HC and PTB groups. The percentage of CD4 + CD25Treg cells was positively correlated with the percentage of CD4T cells only in the PTB group.

Conclusions: This study was the first to show that the proportion of CD8CD28 Treg cells in the peripheral blood of patients with PTB was significantly increased, and the increase in CD8CD28 Treg cells was related to the progression of PTB, which may affect the proportion of immune cell subsets by inhibiting the immune response, resulting in the progression of PTB.
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http://dx.doi.org/10.1186/s12890-022-02088-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338636PMC
July 2022

Awake Mouse fMRI and Pupillary Recordings in the Ultra-High Magnetic Field.

Front Neurosci 2022 6;16:886709. Epub 2022 Jul 6.

Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA, United States.

Awake rodent fMRI is becoming a promising non-invasive brain imaging module when investigating large-scale brain function given behavioral tasks. Previous studies have either applied sedatives during scanning or pre-treatment of anesthetics, e.g., isoflurane, to reduce the motion of animals, which could confound the brain function of "awake" states in rodents. Here, we have established a long training awake mouse fMRI-pupillometry paradigm/setup without the initial use of anesthesia. To validate the awake mouse fMRI platform, evoked BOLD-fMRI was performed to identify brain activation in the visual cortex, dorsal lateral geniculate nuclei, and superior colliculus. Furthermore, pupil signal fluctuation was investigated during scanning, showing a less dilated pupil after 5-8 weeks of intermittent training. Thus, using the awake mouse fMRI with real-time pupillometry provides a longitudinal functional mapping tool to study fully conscious mice.
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http://dx.doi.org/10.3389/fnins.2022.886709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318598PMC
July 2022

Stereoretentive Regio- and Enantioselective Allylation of Isoxazolinones by a Planar Chiral Palladacycle Catalyst.

Angew Chem Int Ed Engl 2022 Jul 28. Epub 2022 Jul 28.

Universität Stuttgart, Institut für Organische Chemie, Pfaffenwaldring 55, Raum 06.301, 70569, Stuttgart, GERMANY.

The catalytic allylic substitution is one of the most important tools in asymmetric synthesis to form C-C bonds in an enantioselective way. While high efficiency was previously accomplished in terms of enantio- and regiocontrol using different catalyst types, a strong general limitation is a very pronounced preference for the formation of allylic substitution products with ( E )-configured C=C double bonds. Herein, we report that with a planar chiral palladacycle catalyst a diastereospecific reaction outcome is achieved using isoxazolinones and allylic imidates as substrates, thus maintaining the C=C double bond geometry of the allylic substrates in the highly enantioenriched products. DFT calculations show that the reactions proceed via an S N 2 mechanism and not via π-allyl Pd complexes. Crucial for the high control is the stabilization of the allylic fragment in the S N 2 transition state by π-interactions with the phenyl substituents of the pentaphenylferrocenyl catalyst core.
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http://dx.doi.org/10.1002/anie.202210145DOI Listing
July 2022

Deficient Caveolin-1 Synthesis in Adipocytes Stimulates Systemic Insulin-independent Glucose Uptake via Extracellular Vesicles.

Diabetes 2022 Jul 26. Epub 2022 Jul 26.

Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.

Caveolin-1 (cav1) is an important structural and signaling component of plasma membrane invaginations called caveolae and is abundant in adipocytes. As previously reported, adipocyte-specific ablation of the cav1 gene (ad-cav1KO mouse) does not result in elimination of the protein, as cav1 protein traffics to adipocytes from neighboring endothelial cells. However, this mouse is a functional knockout as adipocyte caveolar structures are depleted. Compared to controls, ad-cav1KO mice on a high-fat diet (HFD) display improved whole-body glucose clearance despite complete loss of glucose-stimulated insulin secretion, blunted insulin-stimulated AKT activation in metabolic tissues and partial lipodystrophy. The cause is increased insulin-independent glucose uptake by white adipose tissue (AT) and reduced hepatic gluconeogenesis. Furthermore, high fat fed ad-cav1KO mice display significant AT inflammation, fibrosis, mitochondrial dysfunction, and dysregulated lipid metabolism. The glucose clearance phenotype of the ad-cav1KO mice is at least partially mediated by AT small extracellular vesicles (AT-sEVs). Injection of control mice with AT-sEVs from ad-cav1KO mice phenocopies ad-cav1KO characteristics. Interestingly, AT-sEVs from ad-cav1KO mice propagate the phenotype of the AT to the liver. These data indicate that adipocyte cav1 is essential for healthy adaptation of the AT to overnutrition and prevents aberrant propagation of negative phenotypes to other organs by EVs.
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http://dx.doi.org/10.2337/db22-0035DOI Listing
July 2022

Deciphering Prognostic Value of and Its Correlation With Immune Infiltration in Lung Adenocarcinoma.

Front Oncol 2022 8;12:877878. Epub 2022 Jul 8.

Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, School of Medicine, Tongji University, Shanghai, China.

Background: Lung adenocarcinoma (LUAD) is the most common type of lung cancer, accounting for around 40%. Despite achievements in the treatment approach, the prognosis is still dismal, with overall survival of fewer than five years. Thus, novel prognostic biomarkers are needed to predict the clinical outcomes of individual patients better. has a high mutation rate in the LUAD, which encodes a large abundant protein of striated muscle. However, the value of in prognosis and the immune environment are poorly understood.

Methods: We investigated the clinicopathological characteristics, transcriptional and protein level, prognostic value, biological function, and its relationship with immune infiltration of gene in LUAD patients through bioinformatics analysis.

Results: expression was significantly lower in LUAD than that in normal lung tissue. Lower expression was associated with worse survival. Besides, is highly expressed in alveolar type 2 cells which were surmised as the origin of LUAD.

Conclusion: Our findings indicated the potential prognostic value of and its role as a biomarker for determining the immune infiltration levels in patients with LUAD.
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http://dx.doi.org/10.3389/fonc.2022.877878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304871PMC
July 2022

Identification of UCP1 and UCP2 as Potential Prognostic Markers in Breast Cancer: A Study Based on Immunohistochemical Analysis and Bioinformatics.

Front Cell Dev Biol 2022 7;10:891731. Epub 2022 Jul 7.

Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, China.

Uncoupling protein 1 (UCP1) and UCP2 are associated with tumor metabolism and immunity. However, the prognostic value and molecular mechanisms underlying their action in breast cancer (BC) remain unclear. In TCGA-BRCA cohort, we investigated the expression characteristics of UCP mRNAs, analyzed their prognostic value by Kaplan-Meier survival analysis, their potential molecular functions by gene set enrichment analysis, and their relationship with immune infiltrating cell types using TIMER and CIBERSORT, along with the assessment of their association with mutational profiles. Kaplan-Meier survival analysis was performed for UCPs in our cohort and their association with BC thermogenesis was assessed by thermal tomography. High expression of UCP1 and UCP2 were positive prognostic markers for BC. UCP1 was associated with the impaired glucose metabolism, while UCP2 with enhanced anti-tumor immunity. High expressions of UCP1 and UCP2 were associated with CDH1 mutations. High UCP1 expression was associated with a high rate of thermogenesis in BC. These results implied a key role of UCP1 and UCP2 in prognosis, metabolism, and immune infiltration in BC. Further investigation of the relevant molecular mechanisms may provide new strategies for BC treatment.
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http://dx.doi.org/10.3389/fcell.2022.891731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300932PMC
July 2022

Heterogenous Subtypes of Late-Life Depression and Their Cognitive Patterns: A Latent Class Analysis.

Front Psychiatry 2022 6;13:917111. Epub 2022 Jul 6.

Clinical Research Division, Dementia Care and Research Center, Peking University Institute of Mental Health (Sixth Hospital), Beijing, China.

Background: Late-life depression (LLD), characterized by cognitive deficits, is considered heterogeneous across individuals. Previous studies have identified subtypes with diverse symptom profiles, but their cognitive patterns are unknown. This study aimed to investigate the subtypes of LLD and the cognitive profile of each group.

Methods: In total, 109 depressed older adults were enrolled. We performed latent class analysis using Geriatric Depression Scale items as indicators to generate latent classes. We compared the sociodemographic and clinical characteristics with cognitive functions between groups and conducted regression analysis to investigate the association between class membership and variables with significant differences.

Results: Two classes were identified: the "pessimistic" group was characterized by pessimistic thoughts and the "worried" group with a relatively high prevalence of worry symptoms. The two groups did not differ in sociodemographic characteristics. The "pessimistic" group showed a higher rate of past history of depression and lower age of onset. The "worried" group had more physical comorbidities and a higher rate of past history of anxiety. The "pessimistic" group was more impaired in general cognitive function, executive function, information processing speed, and attention. Lower general and executive functions were associated with the membership in the "pessimistic" group.

Conclusions: Subjects with pessimistic symptoms and subjects with a propensity to worry may form two distinct subtypes of late-life depression with different cognitive profiles. Further, the cognitive evaluation of subjects with pessimistic symptoms is of utmost importance.
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http://dx.doi.org/10.3389/fpsyt.2022.917111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9298648PMC
July 2022

Dietary regulation in health and disease.

Signal Transduct Target Ther 2022 07 23;7(1):252. Epub 2022 Jul 23.

Tongji University Cancer Center, Shanghai Tenth People's Hospital of Tongji University, School of Medicine, Tongji University, Shanghai, 200092, China.

Nutriments have been deemed to impact all physiopathologic processes. Recent evidences in molecular medicine and clinical trials have demonstrated that adequate nutrition treatments are the golden criterion for extending healthspan and delaying ageing in various species such as yeast, drosophila, rodent, primate and human. It emerges to develop the precision-nutrition therapeutics to slow age-related biological processes and treat diverse diseases. However, the nutritive advantages frequently diversify among individuals as well as organs and tissues, which brings challenges in this field. In this review, we summarize the different forms of dietary interventions extensively prescribed for healthspan improvement and disease treatment in pre-clinical or clinical. We discuss the nutrient-mediated mechanisms including metabolic regulators, nutritive metabolism pathways, epigenetic mechanisms and circadian clocks. Comparably, we describe diet-responsive effectors by which dietary interventions influence the endocrinic, immunological, microbial and neural states responsible for improving health and preventing multiple diseases in humans. Furthermore, we expatiate diverse patterns of dietotheroapies, including different fasting, calorie-restricted diet, ketogenic diet, high-fibre diet, plants-based diet, protein restriction diet or diet with specific reduction in amino acids or microelements, potentially affecting the health and morbid states. Altogether, we emphasize the profound nutritional therapy, and highlight the crosstalk among explored mechanisms and critical factors to develop individualized therapeutic approaches and predictors.
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http://dx.doi.org/10.1038/s41392-022-01104-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308782PMC
July 2022

LncRNA H19 deficiency protects against the structural damage of glomerular endothelium in diabetic nephropathy via Akt/eNOS pathway.

Arch Physiol Biochem 2022 Jul 22:1-10. Epub 2022 Jul 22.

College of Pharmacy, Xinxiang Medical University, Xinxiang, China.

This study aimed to investigate the functions of lncRNA H19 on glomerular endothelial structural damage of diabetic nephropathy (DN). Rats were fed a high sugar and fat high feed die, and intraperitoneally administrated with streptozotocin (30 mg/kg) to induce DN model. Meanwile, rat glomerular endothelial cells (rGEnCs) were treated with high a level of glucose (HG, 30 mM glucose)to induce structural damage. Our results showed that H19 level was drastically increased in diabetic glomeruli and high-glucose (HG)-stimulated rat glomerular endothelial cells (rGEnCs). Deficiency of H19 ameliorated microalbumin, creatinine, BUN, and histopathological alterations in diabetic rats. In addition, H19 deficiency significantly attenuated the damage of endothelial structure by upregulating the expression of junction proteins ZO-1 and Occludin, glycolcalyx protein Syndecan-1, and endothelial activation marker sVCAM-1 and sICAM-1 in diabetic rats. The results also showed that H19-siRNA alleviated glycocalyx shedding, tight junctions damage, and endothelial activation in HG-stimulated rGEnCs. Moreover, H19 deficiency significantly enhanced the expression of p-Akt and p-eNOS and NO concentration and . Pre-treatment with Akt inhibitor LY294002 abrogated these favourable effects mediated by H19 deficiency. These results indicate that H19 deficiency could mitigate the structural damage of glomerular endothelium in DN via activating Akt/eNOS pathway.
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http://dx.doi.org/10.1080/13813455.2022.2102655DOI Listing
July 2022

Novel Dark Current Reduction Strategy via Deep Bulk Traps for High-Performance Solution-Processed Organic Photodetectors.

ACS Appl Mater Interfaces 2022 Aug 21;14(30):34891-34900. Epub 2022 Jul 21.

School of Optoelectronic Science and Engineering, University of Electronic Science and Technology of China (UESTC), Chengdu 610054, China.

The performance improvement of the organic photodetectors (OPDs) focuses on suppressing the dark current density () to improve the specific detectivity. In this work, a dark current reduction strategy relying on constructing limited deep traps in the active layer to suppress charge injection rate was newly proposed. And an optimization method has been successfully demonstrated on the solution-processed OPDs accordingly. Compared with the expressed by the OPD with the shallow trap system, the device with deep bulk traps exhibits a dramatically reduced dark current while ensuring high responsivity. At a bias of -2 V, the optimized photodiode with a down to 1.4 × 10 mA cm and a maximum responsivity of 0.42 A W @620 nm was realized, leading to a maximum detectivity calculated from shot noise of 6.23 × 10 Jones. This value is 49-fold higher than that of the original OPD with the same structure. The effects of deep traps inside the semiconductor film on injected carriers and photogenerated carriers are well explained by the relative positions of the initial hopping levels. A better understanding of charge transport regimes in OPD helps to open new approaches for constructing high-performance OPD toward practical applications.
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http://dx.doi.org/10.1021/acsami.2c04981DOI Listing
August 2022

The Chinese Brief Cognitive Test: Normative Data Stratified by Gender, Age and Education.

Front Psychiatry 2022 4;13:933642. Epub 2022 Jul 4.

Peking University Institute of Mental Health (Sixth Hospital), Beijing, China.

The aim of this study was to develop a brief version of cognitive assessment test for evaluating the efficacy of treatments targeting cognitive impairments in Chinese schizophrenia patients, to examine its reliability, and establish normative data. Stratified according to age, gender, and educational level, healthy adult subjects were recruited from fifteen institutions in seven administrative regions of China and 723 valid samples were obtained, of which 50 were retested. Generalized Linear Models were conducted to analyze the effects of age, sex, and education. There was no significant difference between genders, while significant effects were demonstrated respectively among age and education on the normative data of C-BCT. The Cronbach α of C-BCT is 0.75, and the test-retest reliability (ICC) ranged from 0.62 to 0.76. Normative data of C-BCT were generated by gender, age and education, and the effects of these demographic factors were analyzed. It revealed good internal consistency and test-retest reliability of C-BCT.
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http://dx.doi.org/10.3389/fpsyt.2022.933642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9289100PMC
July 2022

A Review of Intraocular Pressure (IOP) and Axial Myopia.

J Ophthalmol 2022 9;2022:5626479. Epub 2022 Jul 9.

Department of Ophthalmology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.

The pathogenesis of myopia is driven by genetic and environmental risk factors. Accommodation not only alters the curvature and shape of the lens but also involves contraction of the ciliary and extraocular muscles, which influences intraocular pressure (IOP). Scleral matrix remodeling has been shown to contribute to the biomechanical susceptibility of the sclera to accommodation-induced IOP fluctuations, resulting in reduced scleral thickness, axial length (AL) elongation, and axial myopia. The rise in IOP can increase the burden of scleral stretching and cause axial lengthening. Although the accommodation and IOP hypotheses were proposed long ago, they have not been validated. This review provides a brief and updated overview on studies investigating the potential role of accommodation and IOP in myopia progression.
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http://dx.doi.org/10.1155/2022/5626479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9288324PMC
July 2022

The protocol for assessing olfactory working memory capacity in mice.

Brain Behav 2022 Jul 18:e2703. Epub 2022 Jul 18.

Peking University Institute of Mental Health (Sixth Hospital), Beijing, China.

Background: Working memory capacity (WMC) is the ability to maintain information over a few seconds. Although it has been extensively studied in healthy subjects and neuropsychiatric patients, few tasks have been developed to measure such changes in rodents. Many procedures have been used to measure WM in rodents, including the radial arm maze, the WM version of the Morris swimming task, and various delayed matching and nonmatching-to-sample tasks. It should be noted, however, that the memory components assessed in these procedures do not include memory capacity.

Methods: We developed an olfactory working memory capacity (OWMC) paradigm to assess the WMC of 3-month-old 5×FAD mice, a mouse model of Alzheimer's disease. The task is divided into five phases: context adaptation, digging training, rule learning for nonmatching to a single sample odor (NMSS), rule learning for nonmatching to multiple sample odors (NMMS), and capacity testing.

Results: In the NMSS rule-learning phase, there was no difference between wild-type (WT) mice and 5×FAD mice in the performance correct rate, correct option rate, and correct rejection rate. The WT mice and 5×FAD mice showed similar memory capacity in the NMMS rule-learning phase. After capacity test, we found that the WMC was significantly diminished in 5×FAD mice. As the memory load increased, 5×FAD mice also made significantly more errors than WT mice.

Conclusion: The OWMC task, based on a nonmatch-to-sample rule, is a sensitive and robust behavioral assay that we validated as a reliable method for measuring WMC and exploring different components of memory in mice.
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http://dx.doi.org/10.1002/brb3.2703DOI Listing
July 2022

SHF Acts as a Novel Tumor Suppressor in Glioblastoma Multiforme by Disrupting STAT3 Dimerization.

Adv Sci (Weinh) 2022 Jul 17:e2200169. Epub 2022 Jul 17.

Department of Laboratory Medicine, Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, 214023, China.

Sustained activation of signal transducer and activator of transcription 3 (STAT3) is a critical contributor in tumorigenesis and chemoresistance, thus making it an attractive cancer therapeutic target. Here, SH2 domain-containing adapter protein F (SHF) is identified as a tumor suppressor in glioblastoma Multiforme (GBM) and its negative regulation of STAT3 activity is characterized. Mechanically, SHF selectively binds and inhibits acetylated STAT3 dimerization without affecting STAT3 phosphorylation or acetylation. Additionally, by blocking STAT3-DNMT1 (DNA Methyltransferase 1) interaction, SHF relieves methylation of tumor suppressor genes. The SH2 domain is documented to be essential for SHF's actions on STAT3, and almost entirely replaces the functions of SHF on STAT3 independently. Moreover, the peptide C16 a peptide derived from the STAT3-binding sites of SHF inhibits STAT3 dimerization and STAT3/DNMT1 interaction, and achieves remarkable growth inhibition in GBM cells in vitro and in vivo. These findings strongly identify targeting of the SHF/STAT3 interaction as a promising strategy for developing an optimal STAT3 inhibitor and provide early evidence of the potential clinical efficacy of STAT3 inhibitors such as C16 in GBM.
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http://dx.doi.org/10.1002/advs.202200169DOI Listing
July 2022

Extracellular vesicles derived from adipose-derived stem cells facilitate frostbite wound healing by regulating SOCS3 expression.

Curr Stem Cell Res Ther 2022 Jul 15. Epub 2022 Jul 15.

Department of General Surgery, Jilin University Second Hospital, Changchun, China.

Background: Though adipose-derived stem cells (ADSCs) have potential applications for the repair and regeneration of damaged tissues, limited studies have defined the function of ADSCs on dermal fibroblasts. Our RNA-seq sequencing identified differentially expressed SOCS3 in frostbite injury.

Objective: In the current study, we aim to examine the hypothesis that extracellular vesicles derived from adipose-derived mesenchymal stem cells (ADSCs-EVs) may modulate SOCS3/TGF-β1 signaling in wound healing of frostbite injury.

Methods: sh-SOCS3 and sh-TGF-β1 were introduced to explore the biological role of SOCS3 in frostbite injury, by detecting on the proliferation and migration of human skin fibroblast (HSF) cells and the wound healing in mice. Furthermore, the extracted ADSCs-EVs were interfered with HSF cells in vitro or injected into frostbitten mouse model in vivo.

Results: Upregulation of SOCS3 occurred in the skin tissues of frostbitten mice. Compared to sh-NC, the wound healing rate of sh-SOCS3 presented higher on the day 7(31.34±4.35 vs 41.83±3.74, p < 0.05) and day 14 (63.42±6.01 vs 88.99±5.12, p < 0.05) after injury. Silencing SOCS3 can promote frostbite wound healing. Moreover, SOCS3 downregulated TGF-β1 to suppress the proliferation and migration of HSF cells, thus impeding skin wound healing. Additionally, ADSCs-EVs could enhance the proliferation and migration of HSF cells according to the results of CCK-8 assay (p < 0.05), scratch test(17.82±4.25 vs 49.78±2.54, p < 0.05) and Transwell assay(42.33±6.81 vs 91.33±7.02, p < 0.05), and regulate the expression of SOCS3/TGF-β1. The role of ADSCs-EVs in frostbite wound healing was also confirmed in vivoADSCs-EVs could promote frostbite wound healing by downregulating the expression of SOCS3 and upregulating the expression of TGF-β1 and collagen Conclusions: Collectively, ADSCs-EVs inhibit SOCS3 and facilitate the expression of TGF-β1, which promotes the proliferation and migration of HSF cells and subsequently enhances wound healing of frostbite injury.
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http://dx.doi.org/10.2174/1574888X17666220715094504DOI Listing
July 2022

Accurate 3-DoF Camera Geo-Localization via Ground-to-Satellite Image Matching.

IEEE Trans Pattern Anal Mach Intell 2022 Jul 11;PP. Epub 2022 Jul 11.

We address the problem of ground-to-satellite image geo-localization, that is, estimating the camera latitude, longitude and orientation (azimuth angle) by matching a query image captured at the ground level against a large-scale database with geotagged satellite images. Our prior arts treat the above task as pure image retrieval by selecting the most similar satellite reference image matching the ground-level query image. However, such an approach often produces coarse location estimates because the geotag of the retrieved satellite image only corresponds to the image center while the ground camera can be located at any point within the image. To further consolidate our prior research finding, we present a novel geometry-aware geo-localization method. Our new method is able to achieve the fine-grained location of a query image, up to pixel size precision of the satellite image, once its coarse location and orientation have been determined. Moreover, we propose a new geometry-aware image retrieval pipeline to improve the coarse localization accuracy. Apart from a polar transform in our conference work, this new pipeline also maps satellite image pixels to the ground-level plane in the ground-view via a geometry-constrained projective transform to emphasize informative regions, such as road structures, for cross-view geo-localization. Extensive quantitative and qualitative experiments demonstrate the effectiveness of our newly proposed framework. We also significantly improve the performance of coarse localization results compared to the state-of-the-art in terms of location recalls.
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http://dx.doi.org/10.1109/TPAMI.2022.3189702DOI Listing
July 2022

PM2.5 Synergizes With to Suppress Alveolar Macrophage Function in Mice Through the mTOR Pathway.

Front Pharmacol 2022 21;13:924242. Epub 2022 Jun 21.

School of Life Sciences, Ludong University, Yantai, China.

High concentrations of PM2.5 in enclosed broiler houses cause respiratory disorders in humans and animals. () is an opportunistic pathogen that can induce severe respiratory disease in animals under stress or with abnormal immune functions. Alveolar macrophages are lung-resident immune cells that play important roles in lung host defence and immune balance. In this study, the mechanism by which PM2.5 synergizes with . to damage alveolar macrophage function and induce inflammation was investigated. The results will provide a theoretical basis for improving the poultry breeding environment and preventing the recurrence of infection with . . Alveolar macrophages were stimulated by PM2.5 collected in an enclosed broiler house and . Phagocytosis was determined by the neutral red test. The apoptosis rate and cytoskeleton changes were observed by flow cytometry assays and laser scanning confocal microscopy. Protein levels related to autophagy and the mTOR pathway were detected by Western blotting. The results indicated that PM2.5 in combination with could decrease phagocytosis, inhibit autophagy, increase apoptosis, and destroy the cytoskeleton in alveolar macrophages. In addition, alveolar macrophages had significantly increased expression of mTOR pathway-related proteins in response to the synergistic stimulation of PM2.5 and . The above results confirmed that PM2.5 in poultry houses synergized with to impede alveolar macrophage function and caused more severe respiratory system injuries through a process closely related to the activation of the mTOR signalling pathway.
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http://dx.doi.org/10.3389/fphar.2022.924242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9253536PMC
June 2022

The Monocyte-to-Lymphocyte Ratio Predicts Acute Kidney Injury After Acute Hemorrhagic Stroke.

Front Neurol 2022 20;13:904249. Epub 2022 Jun 20.

Department of Nephrology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.

Objectives: Acute kidney injury (AKI) is a serious complication of acute hemorrhagic stroke (AHS). Early detection and early treatment are crucial for patients with AKI. We conducted a study to analyze the role of the monocyte-to-lymphocyte ratio (MLR) in predicting the development of AKI after AHS.

Methods: This retrospective observational study enrolled all subjects with AHS who attended the neurosurgical intensive care unit (NSICU) at the First Affiliated University of South China between 2018 and 2021. Patient demographics, laboratory data, treatment details, and clinical outcomes were recorded.

Results: Of the 771 enrolled patients, 180 (23.3%) patients developed AKI. Compared to patients without AKI, those with AKI had a higher MLR and the neutrophil-lymphocyte ratio (NLR) at admission ( < 0.001). The MLR and the NLR at admission were associated with an increased AKI risk, with odds ratios (ORs) of 8.27 (95% CI: 4.23, 16.17, < 0.001) and 1.17 (95% CI: 1.12, 1.22, < 0.001), respectively. The receiver operating characteristic curve (ROC) analysis was conducted to analyze the ability of the MLR and NLR to predict AKI, and the areas under the curve (AUCs) of the MLR and the NLR were 0.73 (95% CI: 0.69, 0.77, < 0.001) and 0.67 (95% CI: 0.62, 0.72, < 0.001), with optimal cutoff values of 0.5556 and 11.65, respectively. The MLR and the NLR at admission were associated with an increased in-hospital mortality risk, with ORs of 3.13 (95% CI: 1.08, 9.04) and 1.07 (95% CI: 1.00, 1.14), respectively. The AUCs of the MLR and the NLR for predicting in-hospital mortality were 0.62 (95% CI: 0.54, 0.71, = 0.004) and 0.52 (95% CI: 0.43, 0.62, = 0.568), respectively. The optimal cutoff value for the MLR was 0.7059, with a sensitivity of 51% and a specificity of 73.3%.

Conclusions: MLR and NLR measurements in patients with AHS at admission could be valuable tools for identifying patients at high risk of early AKI. The MLR was positively associated with in-hospital mortality and the NLR showed a weak ability for the prediction of in-hospital mortality.
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http://dx.doi.org/10.3389/fneur.2022.904249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251466PMC
June 2022

Development of Carcinoembryonic Antigen Rapid Detection System Based on Platinum Microelectrode.

Front Chem 2022 20;10:899276. Epub 2022 Jun 20.

School of Basic Medicine, Binzhou Medical University, Yantai, China.

Rapid and highly sensitive detection of carcinoembryonic antigen (CEA) in blood could effectively improve the diagnostic sensitivity of colorectal cancer. In this work, a platinum microelectrode (PtμE) modified with gold nanoparticles was developed as a microsensor for the detection of CEA. As the recognition element, a CEA aptamer modified with sulfhydryl could be conjugated onto the surface of the PtμEs/Au. The quantitative analysis of the concentration of CEA [CEA] by the prepared PtμEs/Au aptasensor was carried out through square wave voltammetry. Under the optimized conditions, the PtμEs/Au aptasensor exhibits a linear response toward [CEA] in the range of 1.0 × 10-1.0 × 10 g/ml (S = 5.5 nA/dec, = 0.999), and the detection limit is 7.7 × 10 g/ml. The PtμEs/Au aptasensor also has good selectivity against other types of proteins existing in blood. The availability of the developed assay toward [CEA] in blood samples was investigated, and the results agreed well with those obtained through electrochemiluminescence provided by the hospital, and the volume of the blood sample for detection is only 20 μl. Herein, the proposed detection system could be used for the quantitative analysis of CEA in blood, with the advantages of high sensitivity, short time, and low cost. Moreover, the PtμEs/Au aptasensor has a potential application in clinical diagnosis.
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http://dx.doi.org/10.3389/fchem.2022.899276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9252266PMC
June 2022

Anterior cingulate glutamate levels associate with functional activation and connectivity during sensory integration in schizophrenia: a multimodal H-MRS and fMRI study.

Psychol Med 2022 Jul 6:1-11. Epub 2022 Jul 6.

Neuropsychology and Applied Cognitive Neuroscience Laboratory, CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.

Background: Glutamatergic dysfunction has been implicated in sensory integration deficits in schizophrenia, yet how glutamatergic function contributes to behavioural impairments and neural activities of sensory integration remains unknown.

Methods: Fifty schizophrenia patients and 43 healthy controls completed behavioural assessments for sensory integration and underwent magnetic resonance spectroscopy (MRS) for measuring the anterior cingulate cortex (ACC) glutamate levels. The correlation between glutamate levels and behavioural sensory integration deficits was examined in each group. A subsample of 20 pairs of patients and controls further completed an audiovisual sensory integration functional magnetic resonance imaging (fMRI) task. Blood Oxygenation Level Dependent (BOLD) activation and task-dependent functional connectivity (FC) were assessed based on fMRI data. Full factorial analyses were performed to examine the Group-by-Glutamate Level interaction effects on fMRI measurements (group differences in correlation between glutamate levels and fMRI measurements) and the correlation between glutamate levels and fMRI measurements within each group.

Results: We found that schizophrenia patients exhibited impaired sensory integration which was positively correlated with ACC glutamate levels. Multimodal analyses showed significantly Group-by-Glutamate Level interaction effects on BOLD activation as well as task-dependent FC in a 'cortico-subcortical-cortical' network (including medial frontal gyrus, precuneus, ACC, middle cingulate gyrus, thalamus and caudate) with positive correlations in patients and negative in controls.

Conclusions: Our findings indicate that ACC glutamate influences neural activities in a large-scale network during sensory integration, but the effects have opposite directionality between schizophrenia patients and healthy people. This implicates the crucial role of glutamatergic system in sensory integration processing in schizophrenia.
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http://dx.doi.org/10.1017/S0033291722001817DOI Listing
July 2022
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