Publications by authors named "Jin Wei"

1,099 Publications

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Strategies to Screen Anti-AQP4 Antibodies from Yeast Surface Display Libraries.

Antibodies (Basel) 2022 Jun 5;11(2). Epub 2022 Jun 5.

Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS 66044, USA.

A rapid and effective method to identify disease-specific antibodies from clinical patients is important for understanding autoimmune diseases and for the development of effective disease therapies. In neuromyelitis optica (NMO), the identification of antibodies targeting the aquaporin-4 (AQP4) membrane protein traditionally involves the labor-intensive and time-consuming process of single B-cell sorting, followed by antibody cloning, expression, purification, and analysis for anti-AQP4 activity. To accelerate patient-specific antibody discovery, we compared two unique approaches for screening anti-AQP4 antibodies from yeast antibody surface display libraries. Our first approach, cell-based biopanning, has strong advantages for its cell-based display of native membrane-bound AQP4 antigens and is inexpensive and simple to perform. Our second approach, FACS screening using solubilized AQP4 antigens, permits real-time population analysis and precision sorting for specific antibody binding parameters. We found that both cell-based biopanning and FACS screening were effective for the enrichment of AQP4-binding clones. These screening techniques will enable library-scale functional interrogation of large natively paired antibody libraries for comprehensive analysis of anti-AQP4 antibodies in clinical samples and for robust therapeutic discovery campaigns.
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http://dx.doi.org/10.3390/antib11020039DOI Listing
June 2022

Effects of resilience on impulsivity, cognition and depression during protracted withdrawal among Chinese male methamphetamine users.

BMC Psychiatry 2022 Jun 21;22(1):414. Epub 2022 Jun 21.

School of Mental Health, Wenzhou Medical University, Chashan Higher Education Park, Ouhai District, Wenzhou, 325000, China.

Background: Methamphetamine (METH) dependence is a complex and dynamic public health problem. Long-term abuse of METH can increase numerous risks of mental and physical problems. Currently, the methods to reduce METH dependence and improve the withdrawal symptoms are limited and ineffective. Resilience is seen as a multidimensional and dynamic capability to recover or bounce back from stressful events and is also generally considered as a protective factor against mental dysfunction.

Methods: One hundred thirty-four males with METH dependence were consecutively recruited from Huanglong Compulsory Isolated Detoxification Center between 2019 and 2021, of whom 112 were into the group. The Connor-Davidson Resilience Scale (CD-RISC), Self-rating depression scale (SDS), Self-rating anxiety scale (SAS), Barratt Impulsiveness Scale-11(BIS-11), and the Repeatable Battery for the Assessment of Neuropsychological Status (Rbans) were used to evaluate resilience, depression, anxiety, impulsivity, and cognition respectively.

Results: The results mainly indicated that high resilience group showed lower SDS, SAS and BIS-11 scores than low resilience group (all p < 0.05). Besides, the total scores of Rbans were higher in high resilience groups than low resilience group (both p < 0.05). Moreover, linear regression results showed that resilience may be influenced by the scores of SDS and SAS.

Conclusions: Resilience is negatively correlated with impulsivity and depression. Besides, it is also positively associated with cognitive function. Drug users with higher resilience may have a strong ability to mobilize psychological resources to create a good psychological environment, which may have a positive effect on the relief or improvement of symptoms.
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http://dx.doi.org/10.1186/s12888-022-04041-8DOI Listing
June 2022

Aberrant stability of brain functional architecture in cirrhotic patients with minimal hepatic encephalopathy.

Brain Imaging Behav 2022 Jun 21. Epub 2022 Jun 21.

Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China.

To investigate the stability changes of brain functional architecture and the relationship between stability change and cognitive impairment in cirrhotic patients. Fifty-one cirrhotic patients (21 with minimal hepatic encephalopathy (MHE) and 30 without MHE (NHE)) and 29 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging and neurocognitive assessment using the Psychometric Hepatic Encephalopathy Score (PHES). Voxel-wise functional connectivity density (FCD) was calculated as the sum of connectivity strength between one voxel and others within the entire brain. The sliding window correlation approach was subsequently utilized to calculate the FCD dynamics over time. Functional stability (FS) is measured as the concordance of dynamic FCD. From HCs to the NHE and MHE groups, a stepwise reduction of FS was found in the right supramarginal gyrus (RSMG), right middle cingulate cortex, left superior frontal gyrus, and bilateral posterior cingulate cortex (BPCC), whereas a progressive increment of FS was observed in the left middle occipital gyrus (LMOG) and right temporal pole (RTP). The mean FS values in RSMG/LMOG/RTP (r = 0.470 and P = 0.001; r = -0.458 and P = 0.001; and r = -0.384 and P = 0.005, respectively) showed a correlation with PHES in cirrhotic patients. The FS index in RSMG/LMOG/BPCC/RTP showed moderate discrimination potential between the NHE and MHE groups. Changes in FS may be linked to neuropathological bias of cognitive impairment in cirrhotic patients and could serve as potential biomarkers for MHE diagnosis and monitoring the progression of hepatic encephalopathy.
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http://dx.doi.org/10.1007/s11682-022-00696-9DOI Listing
June 2022

Water quality assessment of east Tiaoxi River, China, based on a comprehensive water quality index model and Monte-Carlo simulation.

Sci Rep 2022 Jun 16;12(1):10042. Epub 2022 Jun 16.

Zhejiang Provincial Key Laboratory of Solid Waste Treatment and Recycling, School of Environmental Science and Engineering, Zhejiang Gongshang University, Hangzhou, 310018, China.

The comprehensive water quality index (CWQI) reflects the comprehensive pollution status of rivers through mathematical statistics of several water quality indicators. Using computational mathematical simulations, high-confidence CWQI predictions can be obtained based on limited water quality monitoring samples. At present, most of the CWQI reported in the literature are based on conventional indicators such as nitrogen and phosphorus levels, and do not include the petroleum hydrocarbons levels. This article takes a typical river in eastern China as an example, based on the 1-year monitoring at 20 sampling sets, a CWQI containing five factors, TN, NH-N, TP, ∑n-Alks, and ∑PAHs was established, and further predicted by a Monte-Carlo model. The predicted CWQI for each monitoring section is above 0.7, indicating that most of the monitoring sections are moderately polluted, and some sections are seriously polluted. The Spearman rank correlation coefficient analysis results show that TN, ∑PAHs, and ∑n-Alks are the main factors influencing the water quality, especially the petroleum hydrocarbons have a significant impact on the middle and lower reaches due to shipping. In the future, more attention should be paid to petroleum hydrocarbon organic pollutants in the water quality evaluation of similar rivers.
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http://dx.doi.org/10.1038/s41598-022-14293-9DOI Listing
June 2022

Nestin Regulates Keap1-Nrf2-HO-1-Mediated Antioxidant Responses during Stress and Malignant Hematopoiesis.

Authors:
Chunjuan Lu Jin Wei

Biomed Res Int 2022 28;2022:1706585. Epub 2022 May 28.

Department of Nutrition, Heilongjiang Provincial Hospital, Harbin, Heilongjiang 150036, China.

Objective: To investigate the role of nestin in regulating Keap1-nuclear factor erythroid-2-related factor 2 (Nrf2)-heme oxygenase-1-(HO-1-) mediated antioxidant responses in stress and malignant hematopoiesis.

Methods: The mRNA of peripheral blood mononuclear cells was extracted from 20 leukemia patients and 20 healthy people who were hospitalized in the Hematology Department of our hospital from September 2020 to December 2021, and the mRNA levels of nestin, Keap1, Nrf2, and HO-1 were detected by real-time- (RT-) PCR.

Results: Compared with healthy controls, the mRNA of nestin, Keap1, Nrf2, and HO-1 in peripheral blood mononuclear cells of leukemia patients was significantly upregulated.

Conclusion: The occurrence and development of leukemia are closely related to nestin regulating Keap1-Nrf2-Ho-1 signal pathway. . This study determined the effect of nestin on the biological behavior of leukemia cells and its possible mechanism and confirmed that nestin may be a marker of tumor and tumor blood vessels.
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http://dx.doi.org/10.1155/2022/1706585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9167119PMC
June 2022

SIRT2-KLF4 Interactions are Critical for Myeloma Survival and Migration.

Authors:
Chunjuan Lu Jin Wei

Comput Intell Neurosci 2022 27;2022:7356477. Epub 2022 May 27.

Department of Nutrition, Heilongjiang Provincial Hospital, Harbin, Heilongjiang 150036, China.

Objective: To investigate the roles and possible mechanisms of SIRT2 and KLF4 in the development and progression of myeloma.

Methods: Rt-PCR was used to detect SIRT2 in myeloma samples from patients and myeloma cells, the expression level of KLF4 in myeloma cells, and the effect of downregulation of SIRT2 expression on KLF4 expression level. MTT assay and wound-healing assay were used to observe the proliferation and migration of U266cells transient transfected with Sirt2 inhibitors.

Results: SIRT2 is highly expressed in myeloma, but KLF4 was down. Downregulation of SIRT2 expression stimulated the expression level of KLF4. Reduced SIRT2 activity results in the release of KLF4 expression, which inhibits the proliferation and migration of myeloma cells.

Conclusion: SIRT2-KLF4 combination plays an important role in the occurrence and development of myeloma.
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http://dx.doi.org/10.1155/2022/7356477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9166995PMC
June 2022

Clinical Data Analysis for Treatment of Adult Inguinal Hernia by TAPP or TEP.

Front Surg 2022 20;9:900843. Epub 2022 May 20.

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

Background: Transabdominal preperitoneal (TAPP) repair and totally extraperitoneal (TEP) repair are the primary surgical methods for the treatment of adult inguinal hernia, but it remains necessary to consider which one to choose in clinical practice. Our study seeks to compare the efficacy of laparoscopic TAPP and laparoscopic TEP in the treatment of adult inguinal hernia and to explore which surgical method is a better choice.

Methods: A retrospective analysis of 686 adult patients with inguinal hernia admitted to our hospital from the period January 2016 to December 2020 was conducted. According to different surgical methods, they were divided into two groups: a TAPP group ( = 361) and a TEP group ( = 325). These two groups of patients were statistically analyzed, and the operation time, postoperative pain, postoperative hospital stay length, postoperative complications, and recurrence rate were compared between them.

Results: There were no significant differences in postoperative hospital stay, complications, and the recurrence rate between the two groups (> 0.05). The duration of operation in the TEP group was significantly shorter than that in the TAPP group, and the difference was statistically significant (< 0.001); in terms of postoperative pain, the TEP group fared better than the TAPP group, and the difference was statistically significant (< 0.001).

Conclusion: TAPP and TEP are safe and effective surgical methods in the treatment of adult inguinal hernia. However, compared with TAPP, TEP can significantly shorten the operative time, reduce intraoperative trauma, and limit postoperative pain in the treatment of adult inguinal hernia. Furthermore, it does not increase the rate of complications or recurrence, so it is worth popularizing.
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http://dx.doi.org/10.3389/fsurg.2022.900843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9163490PMC
May 2022

An unusual cause of protuberant lesion of gastric body.

Asian J Surg 2022 May 26. Epub 2022 May 26.

Department of Gastroenterology, Suzhou Ninth People's Hospital, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2022.05.083DOI Listing
May 2022

Quantitative proteomics reveals the antibiotics adaptation mechanism of Aeromonas hydrophila under kanamycin stress.

J Proteomics 2022 Jul 24;264:104621. Epub 2022 May 24.

National Engineering Research Center of JUNCAO Technology, Fujian Agriculture and Forestry University, Fuzhou 350002, China. Electronic address:

Aeromonas hydrophila is a widespread opportunistic pathogen of aquatic fishes in freshwater habitats. The current emergence of antimicrobial-resistant A. hydrophila has been reported in the world while the bacterial antibiotics adaptive mechanism remains poorly explored. In this study, using quantitative proteomics technology, the behavior of A. hydrophila was investigated by comparing the differentially expression proteins between with and without kanamycin (KAN) treatment. A total of 374 altered proteins including 184 increasing and 190 proteins decreasing abundances were quantified when responding to KAN stress. The bioinformatics analysis showed that stress related proteins were hub proteins that significantly increased to reduce the pressure from the misreading of mRNA caused by KAN. Moreover, several metallic pathways, such as oxidative phosphorylation and TCA cycle pathways may affect KAN resistance. Finally, eight selected genes were deleted and their antibiotics susceptibilities to kanamycin were valued, respectively. Results showed that OmpA II family protein A0KI26, and two-component system protein AtoC may involve in the KAN resistance in this study. In general, our results provide an insight into the behaviors of bacterial responding to KAN stress, and demonstrate the intrinsic antibiotics adaptive mechanism of A. hydrophila. BIOLOGICAL SIGNIFICANCE: In this study, the differentially expressed proteins (DEPs) of A. hydrophila strain between with and without kanamycin (KAN) were compared by using a data-independent acquisition (DIA) - based quantitative proteomics method. Bioinformatics analysis showed that stress - related proteins are hub proteins that significantly increased under KAN stress. Moreover, several metallic pathways, such as oxidative phosphorylation and citrate cycle (TCA cycle) pathways, can affect KAN resistance. Finally, our antibiotics susceptibility assay showed that the protein A0KI26 of the OmpA II family, and the AtoC of the two-component system may involve in KAN resistance in this study. These results provide insights into the antibiotics adaptation mechanism of A. hydrophila when responding to KAN stress.
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http://dx.doi.org/10.1016/j.jprot.2022.104621DOI Listing
July 2022

The impact of blastomere loss on pregnancy and neonatal outcomes of vitrified-warmed Day3 embryos in single embryo transfer cycles.

J Ovarian Res 2022 May 18;15(1):62. Epub 2022 May 18.

Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.

Background: Blastomere loss is a common phenomenon that occurs following cryopreservation. To date, studies have drawn conflicting conclusions regarding the impact of blastomere loss on pregnancy outcomes. Besides, limited information is available concerning the neonatal safety of embryos with blastomere loss. In the present study, we aimed to investigate the impact of blastomere loss on pregnancy and neonatal outcomes of vitrified/warmed Day3 cleavage-stage embryos in single embryo transfer cycles.

Methods: This retrospective cohort study included all vitrified/warmed D3 cleavage-stage single frozen-thawed embryo transfer (FET) cycles between April 2015 and February 2021. We compared pregnancy and subsequent neonatal outcomes between the intact embryos group and the blastomere loss group in single FET cycles.

Results: A total of 6287 single FET cycles were included in the study, in which 5873 cycles were classified into the intact embryo group and 414 cycles were classified into the blastomere loss group. The outcomes of the blastomere loss group were significantly inferior to those of the intact embryo group, in terms of implantation/biochemical pregnancy/clinical pregnancy/ongoing pregnancy rate and live birth rate per embryo transfer cycle/per clinical pregnancy. Further binary logistic regression confirmed that blastomere loss was negatively associated with live birth. Moreover, the blastomere loss group presented with an elevated early miscarriage rate. The neonatal conditions were broadly similar between the two groups. Additionally, multiple binary logistic regression analysis demonstrated that primary infertility and intracytoplasmic sperm injection (ICSI) were common influencing factors of blastomere loss (aOR 1.447, 95% CI 1.038-2.019, P = 0.029; aOR: 1.388, 95% CI: 1.044-51.846, P = 0.024).

Conclusions: The transfer of vitrified/warmed D3 embryos with blastomere loss is related to impaired embryo developmental potentials and reduced probabilities of conception. Moreover, even if the embryos with blastomere loss have implanted and reached clinical pregnancies, they present with a lower possibility of developing to live birth owing to a higher early miscarriage rate. However, once the embryos with blastomere loss result in a live birth, no adverse neonatal outcomes are observed. Primary infertility and ICSI were found to be risk factors for blastomere loss.
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http://dx.doi.org/10.1186/s13048-022-00997-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9116052PMC
May 2022

NSrp70 suppresses metastasis in triple-negative breast cancer by modulating Numb/TβR1/EMT axis.

Oncogene 2022 06 14;41(25):3409-3422. Epub 2022 May 14.

Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.

Alternative splicing of mRNA precursors allows cancer cells to create different protein isoforms that promote growth and survival. Compared to normal cells, cancer cells frequently exhibit a higher diversity of their transcriptomes. A comprehensive understanding of splicing regulation is required to correct the splicing alterations for the future precision oncology. A quantitative proteomic screen was performed to identify the regulators associated the metastasis in triple-negative breast cancer. Multiple in vitro and in vivo functional analyses were used to study the effects of NSrp70 on breast cancer metastasis. Next, transcriptomic sequencing (RNA-seq) and alternative splicing bioinformatics analysis was applied to screen the potential targets of NSrp70. Moreover, in vitro splicing assays, RNA pull-down, and RNA immunoprecipitation assay were used to confirm the specific binding between NSrp70 and downstream target genes. Furthermore, the prognostic value of NSrp70 was analyzed in a cohort of patients by performing IHC. We uncovered NSrp70 as a novel suppressor of breast cancer metastasis. We discovered that NSrp70 inhibited the skipped exon alternative splicing of NUMB, promoted the degradation of transforming growth factor receptor 1 through lysosome pathway, and regulated TGFβ/SMAD-mediated epithelial-mesenchymal transition phenotype in breast cancer cells. Furthermore, high NSrp70 expression correlated with a better prognosis in breast cancer patients. Our findings revealed that splicing regulator NSrp70 serves as a metastasis suppressor.
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http://dx.doi.org/10.1038/s41388-022-02349-zDOI Listing
June 2022

The Network Pharmacology Study of Dahuang Fuzi Decoction for Treating Incomplete Intestinal Obstruction.

Biomed Res Int 2022 28;2022:2775434. Epub 2022 Apr 28.

Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610075, China.

Objective: To explore the mechanism of Dahuang Fuzi decoction in the treatment of incomplete intestinal obstruction (IIO) based on network pharmacology and molecular docking.

Methods: The chemical components of Rhubarb, Aconite, and Asarum were searched by the Traditional Chinese Medicine Systems Pharmacology database, where the possible active components were screened by oral bioavailability and drug likeness as filtering indicators. The relevant targets in the Swiss Target Prediction database were obtained according to the structure of the chemical components confirmed by the PubChem database. Disease targets of IIO were collected using GeneCards and OMIM databases. We obtained the cross-target using VENNY to capture the common targets. PPI analysis was performed on the intersection genes combined with Cytoscape 3.7.2. Gene Ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out by David database. The core targets and active ingredients were molecularly docked through AutoDock Vina software to predict the detailed molecular mechanism of Dahuang Fuzi decoction for treating IIO.

Results: There are 45 active components in Dahuang Fuzi decoction, with 709 corresponding targets, 538 IIO targets, and 97 common targets, among which kaempferol, deltoin, and eupatin are the main active ingredients. 10 core targets were obtained by protein-protein interaction network analysis. Through GO enrichment analysis, it was found that Dahuang Fuzi decoction may be involved in biological processes such as signal transduction, anti-apoptosis, promotion of gene expression, regulation of cell proliferation, and differentiation. Besides, KEGG pathway analysis revealed that it mainly relates to PI3K-AKT signal pathway and HIF-1 signal pathway, etc. Molecular docking results showed that the active ingredients of Dahuang Fuzi decoction possess a good binding activity with the core targets.

Conclusion: Dahuang Fuzi decoction may act on target genes such as TNF, IL6, AKT1, VEGFA, SRC, EGFR, and STAT3 through active ingredients such as kaempferol, deltoin, and eupatin to regulate signaling pathways such as PI3K-AKT and HIF-1 and reduce the expression of various inflammatory factors such as TNF-, IL-6, iNOS, and COX-2 to play a role in the treatment of IIO.
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http://dx.doi.org/10.1155/2022/2775434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9071898PMC
May 2022

Illuminated border: Spatiotemporal analysis of COVID-19 pressure in the Sino-Burma border from the perspective of nighttime light.

Int J Appl Earth Obs Geoinf 2022 May 26;109:102774. Epub 2022 Apr 26.

School of Earth Sciences, Yunnan University, Kunming 650500, China.

The emergence of mutant strains such as Omicron has increased the uncertainty of COVID-19, and all countries have taken strict measures to prevent the spread of the disease. The spread of the disease between countries is of particular concern. However, most COVID-19 research focuses mainly on the country or community, and there is less research on the border areas between two countries. In this study, we analyzed changes in the total nighttime light intensity (TNLI) and total nighttime lit area (TNLA) along the Sino-Burma border and used the data to construct an epidemic pressure input index (PII) model in reference to the Shen potential model. The results show that, as the epidemic became more severe, TNLI on both sides of the border at the Ruili border port increased, while that in areas far from the port decreased. At the same time, increases and decreases in TNLA occurred in areas far from the port, and PII can indicate the areas where imported cases are likely to occur. Along the Sino-Burma border, the PII model showed low PII in the north and south and high PII in the central region. The areas between Dehong and Lincang, especially the Ruili, Wanding, Nansan, and Qingshuihe border ports, had high PII. The results of this study offer a reference for public health officials and decision makers when determining resource allocation and the implementation of stricter quarantine rules. With updated epidemic statistics, PII can be recalculated to support timely monitoring of COVID-19 in border areas.
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http://dx.doi.org/10.1016/j.jag.2022.102774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9040464PMC
May 2022

Total Cerebral Small Vessel Disease Score and Cerebral Bleeding Risk in Patients With Acute Stroke Treated With Intravenous Thrombolysis.

Front Aging Neurosci 2022 11;14:790262. Epub 2022 Apr 11.

Department of Neurology, Stroke Research Center, Fujian Medical University Union Hospital, Fuzhou, China.

Objective: The aim of this study was to investigate the association of total cerebral small vessel disease (cSVD) score with the risk of intracerebral hemorrhage (ICH) in patients with acute ischemic stroke who received intravenous thrombolysis (IVT) using recombinant tissue-plasminogen activator (rt-PA).

Methods: We retrospectively reviewed clinical data from two stroke registries of patients with acute ischemic stroke treated with IVT. We assessed the baseline magnetic resonance (MR) visible cSVD markers and total cSVD score (ranging from 0 to 4) between patients with and without ICH after IVT. Logistic regression analysis was used to determine the association of total cSVD score with the risk of ICH after IVT, adjusted for cofounders selected by least absolute shrinkage and selection operator (LASSO). We additionally performed an -value analysis to fully explain away a specific exposure-outcome association. Receiver operating characteristic (ROC) curve analysis was used to quantify the predictive potential of the total cSVD score for any ICH after IVT.

Results: Among 271 eligible patients, 55 (20.3%) patients experienced any ICH, 16 (5.9%) patients experienced a symptomatic ICH (sICH), and 5 (1.85%) patients had remote intracranial parenchymal hemorrhage (rPH). Logistic regression analysis showed that the risk of any ICH increased with increasing cSVD score [per unit increase, adjusted odds ratio (OR) 2.03, 95% CI 1.22-3.41, = 0.007]. Sensitivity analyses using -value revealed that it would need moderately robust unobserved confounding to render the exposure-outcome (cSVD-any ICH) association null. ROC analysis showed that compared with the National Institutes of Health Stroke Scale (NIHSS) score alone, a combination of cSVD and NIHSS score had a larger area under the curve for any ICH (0.811, 95% CI 0.756-0.866 vs. 0.784, 95% CI 0.723-0.846, = 0.0004).

Conclusion: The total cSVD score is associated with an increased risk of any ICH after IVT and improves prediction for any ICH compared with NIHSS alone.
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http://dx.doi.org/10.3389/fnagi.2022.790262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9037754PMC
April 2022

Blood Neutrophil-to-Lymphocyte Ratio as a Predictor of Cerebral Small-Vessel Disease.

Med Sci Monit 2022 Apr 26;28:e935516. Epub 2022 Apr 26.

Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland).

BACKGROUND In recent studies, neutrophil-to-lymphocyte ratio (NLR) was reported to be a good predictor of acute ischemic stroke (AIS), but its role in cerebral small-vessel disease (CSVD) is still controversial. We aimed to explore the value of NLR to identify CSVD. MATERIAL AND METHODS We enrolled 466 CSVD patients and 413 controls. The total burden score of CSVD was calculated according to MRI results, and imaging subgroups were divided according to MRI. The 90-day outcome was evaluated using the modified Rankin scale (mRS). NIHSS score, mRS, clinical information, biochemical parameters, and NLR were recorded, and we analyzed the relationship between NLR and CSVD. RESULTS NLR was a risk factor for CSVD (OR 1.58, 95%CI 1.015~1.322; P=0.029). NLR was positively correlated with CSVD (r=0.259; P=0.001). The AUC was 0.774, with a cut-off value of 1.89 (95% CI 0.742~0.806), P=0.000. NLR was significantly different among the different total burden score groups of CSVD (P=0.009). NLRs were significant different among enlarged perivascular space (EPVS) groups (P=0.017), periventricular white matter high signal (PWMHS) groups (P=0.028), and deep white matter high signal (DWMHS) groups (P=0.004), but no significant difference was found among cerebral microbleeds (CMBs) groups (P=0.118). NLR was correlated with short-term outcome of CSVD (P=0.000). The AUC was 0.732 (95% CI 0.684~0.779), with a cut-off value of 2.413 for predicting a poor CSVD prognosis. CONCLUSIONS NLR has potential diagnostic value for CSVD, and it can predict the short-term outcome of CSVD. Therefore, NLR may be a useful biomarker to predict CSVD and its outcome.
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http://dx.doi.org/10.12659/MSM.935516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9057675PMC
April 2022

Pulmonary embolism and bradycardia in a NSCLC patient treated with crizotinib for a rare mutation.

J Oncol Pharm Pract 2022 Apr 24:10781552221091595. Epub 2022 Apr 24.

Department of Cardiovascular Medicine, 66281Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.

Introduction: Lung cancer is a major global health problem because of its high incidence and mortality. Targeted therapies have transformed treatment of driver-mutated metastatic non-small cell lung cancer (NSCLC). Nevertheless, recent studies demonstrated that cardiovascular disease (CVD) was the second leading cause of mortality in cancer survivors now, management of patients' cardiovascular health during the course of anticancer therapy has become a great challenge faced by the oncologists. Anticancer related cardiovascular (CV) complications are not limited to traditional chemotherapy, but are also increasingly recognized in targeted therapy.

Case Report: We present a case of pulmonary embolism (PE) and bradycardia in a 91-year-old NSCLC patient treated with crizotinib for a rare MET Y1003S mutation. To our knowledge, this is the second report to show antitumor response of crizotinib in lung cancer patients with such a rare mutation. However, the patient complained chest tightness and shortness of breath after a month of standard dose crizotinib therapy. Non-invasive examination revealed new onset bradycardia and PE.

Management & Outcome: Such clinical manifestations were associated with targeted therapy-related CV toxicity, on which the emerging discipline cardio-oncology focused, and a multidisciplinary investigation and treatment was conducted.

Discussion: This case highlights the CV adverse events of novel therapies and the current challenges to be tackled in cardio-oncology.
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http://dx.doi.org/10.1177/10781552221091595DOI Listing
April 2022

Dual-comb photothermal spectroscopy.

Nat Commun 2022 Apr 21;13(1):2181. Epub 2022 Apr 21.

Department of Mechanical and Automation Engineering, and Shenzhen Research Institute, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, China.

Dual-comb spectroscopy (DCS) has revolutionized optical spectroscopy by providing broadband spectral measurements with unprecedented resolution and fast response. Photothermal spectroscopy (PTS) with a pump-probe configuration offers a highly sensitive gas sensing method, which is normally performed using a single-wavelength pump laser. The merging of PTS with DCS may enable a spectroscopic method by taking advantage of both technologies, which has never been studied yet. Here, we report dual-comb photothermal spectroscopy (DC-PTS) by passing dual combs and a probe laser through a gas-filled anti-resonant hollow-core fiber, where the generated multi-heterodyne modulation of the refractive index is sensitively detected by an in-line interferometer. As an example, we have measured photothermal spectra of acetylene over 1 THz, showing a good agreement with the spectral database. Our proposed DC-PTS provides opportunities for broadband gas sensing with super-fine resolution and high sensitivity, as well as with a small sample volume and compact configuration.
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http://dx.doi.org/10.1038/s41467-022-29865-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023540PMC
April 2022

Pharmacist-led standardization of total parenteral nutrition improves postoperative nutritional status in colorectal cancer patients.

Ann Transl Med 2022 Mar;10(6):339

Department of Pharmacy, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China.

Background: Total parenteral nutrition (TPN) is an essential treatment for patients who undergo abdominal surgery. Due to the gap of knowledge background between clinicians and pharmacists, the participation of the latter may improve TPN standardization. However, the impact on clinical outcome is unknown. In this study, we evaluated the impact of appropriacy and efficacy of TPN prescription, after a pharmacist-led TPN standardization program introduced.

Methods: A pharmacist-led TPN standardization program was introduced in the Zhejiang Cancer Hospital and the clinical outcomes were assessed. The TPN standardization program includes a pre-established standard multidisciplinary evaluation standard, a computerized TPN management system and regular evaluations of TPN prescription performed by pharmacists. Any concerns were identified and improved via discussed with doctors. To evaluate the effect of pharmacists' intervention in nutritional status and postoperative complications, an observational before-and-after cohort study was performed. All patients admitted in hospital with colorectal cancer (CRC) and receiving abdominal surgery in June 2019 (pre-intervention cohort) and June 2020 (post-intervention cohort) were retrospectively analyzed. Nutritional status of patients was evaluated using the levels of postoperative serum albumin, prealbumin, total protein, and their decrease extent. Surgical or TPN-related complications and recovery time were collated as the clinical outcomes.

Results: There were no significant differences in the basic clinical information of the two cohorts, suggesting that the two groups are comparable. The average postoperative prealbumin levels were elevated in 2020 compared to 2019 (192.3±5.5 mg/L for 2019 and 229.5±4.8 mg/L for 2020, P<0.001). In addition, the post-intervention cohort showed a lower postoperative infection rate (11.6% 18.2%), shorter duration of infection (9.4±1.4 7.7±1.0 days), lower incidence of postoperative albumin decrease (25.2% 76.7%), prealbumin decrease (71.5% 78.9%), and total protein decrease (25.2% 72.2%), and lower incidence of TPN-related hypoglycemia (5.4% 15.3%).

Conclusions: Pharmacist-led TPN standardization improved the postoperative clinical outcomes in patients with colorectal cancer (CRC).
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http://dx.doi.org/10.21037/atm-22-1172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9011228PMC
March 2022

Generation of a human induced pluripotent stem cell (iPSC) line from skin fibroblasts of a patient carrying an E363Q mutation in PSEN1 gene.

Stem Cell Res 2022 05 28;61:102769. Epub 2022 Mar 28.

State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China; Neuroscience Center, Chinese Academy of Medical Sciences, Beijing 100005, China. Electronic address:

Alzheimer's disease (AD) is a common neurodegenerative disease characterized by cognitive decline even leading to incapacity, which prevalence estimates that about 5% of AD cases are caused by mutations in genes such as Presenilin-1 (PSEN1). Here we report the generation and characterization of an iPSC line derived from a patient carrying an E363Q mutation in PSEN1 gene. The iPSC line we generated presented a typical morphology, normal karyotype, free from Sendai viral vectors and exogenous factors, expressed endogenous pluripotency marker genes and proteins, which could form embryoid bodies in vitro and form teratoma in vivo as well, demonstrating its pluripotency.
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http://dx.doi.org/10.1016/j.scr.2022.102769DOI Listing
May 2022

Density Functional Investigation on α-MoO (100): Amines Adsorption and Surface Chemistry.

ACS Sens 2022 Apr 8;7(4):1213-1221. Epub 2022 Apr 8.

Institute of Microscale Optoelectronics, Collaborative Innovation Centre for Optoelectronic Science & Technology, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen Key Laboratory of Micro-Nano Photonic Information Technology, Guangdong Laboratory of Artificial Intelligence and Digital Economy (SZ), Shenzhen University, Shenzhen 518060, China.

The (100) surface of α-MoO should possess overwhelmingly more exposed Mo atoms than the (010), and the exposed Mo has been extensively considered as an active site for amine adsorption. However, α-MoO (100) has drawn little attention concerning the amine sensing mechanism. In this research, adsorption of ammonia (NH), monomethylamine (MMA), dimethylamine (DMA), and trimethylamine (TMA) is systematically investigated by density functional theory (DFT). All four of these molecules have high affinity to α-MoO (100) through interaction between the N and the exposed Mo, and the affinity is mainly influenced by both the characteristics of the molecules and the geometric environment of the surface active site. Adsorption and dissociation of water and oxygen molecule on stoichiometric and defective α-MoO (100) surfaces are then simulated to fully understand the surface chemistry of α-MoO (100) in practical conditions. At low temperature, α-MoO (100) must be covered with a large number of water molecules; the water can desorb or dissociate into hydroxyl groups at high temperature. Oxygen vacancy (V) can be generated through the annealing process during sensor device fabrication; V must be filled with an O molecule, which can further interact with adsorbed water nearby to form hydroxyl groups. According to this research, α-MoO (100) must be the active surface for amine sensing and its surface chemistry is well understood. In the near future, further reaction and interaction will be simulated at α-MoO (100), and much more attention should be paid to α-MoO (100) not only theoretically but also experimentally.
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http://dx.doi.org/10.1021/acssensors.2c00352DOI Listing
April 2022

Nuclear Tkt promotes ischemic heart failure via the cleaved Parp1/Aif axis.

Basic Res Cardiol 2022 04 5;117(1):18. Epub 2022 Apr 5.

Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200023, People's Republic of China.

Transketolase (Tkt), an enzyme in pentose phosphate pathway, has been reported to regulate genome instability and cell survival in cancers. Yet, the role of Tkt after myocardial ischemic injury remains to be elucidated. Label-free proteomics revealed dramatic elevation of Tkt in murine hearts after myocardial infarction (MI). Lentivirus-mediated Tkt knockdown ameliorated cardiomyocyte apoptosis and preserved the systolic function after myocardial ischemic injury. In contrast, Tkt overexpression led to the opposite effects. Inducible conditional cardiomyocyte Tkt-knockout mice were generated, and cardiomyocyte-expressed Tkt was found to play an intrinsic role in the ischemic heart failure of these model mice. Furthermore, through luciferase assay and chromatin immunoprecipitation, Tkt was shown to be a direct target of transcription factor Krüppel-like factor 5 (Klf5). In cardiomyocytes under ischemic stress, Tkt redistributed into the nucleus. By binding with the full-length poly(ADP-ribose) polymerase 1 (Parp1), facilitating its cleavage, and activating apoptosis inducible factor (Aif) subsequently, nuclear Tkt demonstrated its non-metabolic functions. Overall, our study confirmed that elevated nuclear Tkt plays a noncanonical role in promoting cardiomyocyte apoptosis via the cleaved Parp1/Aif pathway, leading to the deterioration of cardiac dysfunction.
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http://dx.doi.org/10.1007/s00395-022-00925-8DOI Listing
April 2022

Exercise training improves cardiac function and regulates myocardial mitophagy differently in ischaemic and pressure-overload heart failure mice.

Exp Physiol 2022 Jun 19;107(6):562-574. Epub 2022 Apr 19.

Department of Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, China.

New Findings: What is the central question of this study? What are the cardioprotective effects of different aerobic exercises on chronic heart failure with different aetiologies, and is mitophagy involved? What is the main finding and its importance? Moderate-intensity continuous training may be the 'optimum' modality for improving cardiac structure and function in ischaemic heart failure, while both moderate-intensity continuous training and high-intensity interval training were suitable for pressure-overload heart failure. Various mitophagy pathways, especially parkin-dependent pathways, participated in the protective effects of exercise on heart failure.

Abstract: The cardioprotective effects of different aerobic exercises on chronic heart failure with different aetiologies and whether mitophagy is involved remain elusive. In the current research, left anterior descending ligation and transverse aortic constriction surgeries were used to establish mouse models of heart failure, followed by 8 weeks of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT). The results showed that for ischaemic heart failure MICT significantly improved ejection fraction (P < 0.05) and fractional shortening (P < 0.05), mitigated left ventricular end-systolic dimension (P < 0.01), decreased brain natriuretic peptide (P < 0.0001) and mitigated fibrosis (P < 0.0001), while HIIT only decreased brain natriuretic peptide (P < 0.0001) and fibrosis (P < 0.0001). For pressure-overload heart failure, both MICT and HIIT significantly increased ejection fraction (P < 0.0001) and fractional shortening (MICT: P < 0.001, HIIT: P < 0.0001), and reduced left ventricular end-diastolic and end-systolic dimensions, brain natriuretic peptide (P < 0.0001), and fibrosis (MICT: P < 0.01, HIIT: P < 0.0001); HIIT was even better in reducing brain natriuretic peptide. Myocardial autophagy and mitophagy were compromised in heart failure, and the exercises improved myocardial autophagic flux and mitophagy inconsistently in heart failure with different aetiologies. Significant correlations were found between multiple mitophagy pathways and the cardioprotection of the exercises. Collectively, MICT may be the 'optimum' modality for ischaemic heart failure, while both MICT and HIIT (especially HIIT) were suitable for pressure-overload heart failure. Exercises differently improved myocardial autophagy/mitophagy, and multiple mitophagy-related pathways were closely implicated in cardioprotection of exercises for chronic heart failure.
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http://dx.doi.org/10.1113/EP090374DOI Listing
June 2022

Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617.

Nat Commun 2022 03 28;13(1):1638. Epub 2022 Mar 28.

Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.

COVID-19 pathogen SARS-CoV-2 has infected hundreds of millions and caused over 5 million deaths to date. Although multiple vaccines are available, breakthrough infections occur especially by emerging variants. Effective therapeutic options such as monoclonal antibodies (mAbs) are still critical. Here, we report the development, cryo-EM structures, and functional analyses of mAbs that potently neutralize SARS-CoV-2 variants of concern. By high-throughput single cell sequencing of B cells from spike receptor binding domain (RBD) immunized animals, we identify two highly potent SARS-CoV-2 neutralizing mAb clones that have single-digit nanomolar affinity and low-picomolar avidity, and generate a bispecific antibody. Lead antibodies show strong inhibitory activity against historical SARS-CoV-2 and several emerging variants of concern. We solve several cryo-EM structures at ~3 Å resolution of these neutralizing antibodies in complex with prefusion spike trimer ectodomain, and reveal distinct epitopes, binding patterns, and conformations. The lead clones also show potent efficacy in vivo against authentic SARS-CoV-2 in both prophylactic and therapeutic settings. We also generate and characterize a humanized antibody to facilitate translation and drug development. The humanized clone also has strong potency against both the original virus and the B.1.617.2 Delta variant. These mAbs expand the repertoire of therapeutics against SARS-CoV-2 and emerging variants.
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http://dx.doi.org/10.1038/s41467-022-29288-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8960874PMC
March 2022

Identification of Preoperative Serum Metabolites Associated With Postoperative Opioid Consumption in Gastric Cancer Patients by Extreme Phenotype Sampling.

Pain Physician 2022 03;25(2):E385-E396

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Anesthesiology, Peking University Cancer Hospital & Institute, Beijing, China.

Background: Postoperative pain increases patients' risk and opioids remain the main analgesics to relieve it. However, improper use of opioids causes many side effects and identification of suitable preoperative biomarkers that predict postoperative opioid consumption may aid clinicians in improving analgesic strategies for patients. The activity of metabolites modulates multiple phenotypes and can function as biomarkers for disease prediction and diagnosis.

Objectives: In this study, we explore whether preoperative serum metabolites are associated with postoperative opioid consumption in gastric cancer patients by extreme phenotype sampling.

Study Design: This was a case-control, observational study.

Setting: This study was conducted at Beijing Cancer Hospital.

Methods: One hundred and sixty-nine gastric cancer patients participated in this study. After exclusion of 51 patients, postoperative pain intensity and opioid consumption data of 118 patients were collected. Patients were sorted by gender and classified into 2 groups based on opioid consumption during the 24h postoperative period. Patients in the sufentanil high consumption (SHC) group and patients in the sufentanil low consumption (SLC) group were ranked in the top or bottom 30% of sufentanil consumption, respectively. Untargeted metabolomic analysis of preoperative serum samples from both groups was performed by ultra-performance liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) and orthogonal partial least square discriminant analysis. Allele frequencies of DAO rs10156191 and MAOB rs1799836 SNPs in both groups were detected by Sanger sequencing.

Results: Thirty-five metabolites in preoperative serum were significantly different between the SLC and SHC groups. Hydrogen phosphate had the highest area under the curve in a ROC analysis (0.98), suggesting that it may serve as a predictive biomarker for postoperative opioid consumption. Differential metabolites unique to the male and female subgroups were also identified. Histidine metabolism was the most altered pathway between the SLC and SHC groups. There were no significant differences in the allele frequencies of 2 SNPs associated with histamine degradation; however, 2 metabolites of histamine degradation, imidazole-4-acetaldehyde, and methylimidazole acetaldehyde, showed different trends in the 2 groups.

Limitations: Our study was restricted to gastric cancer patients with strict exclusion criteria, which may limit the generalizability to other groups.

Conclusion: Preoperative serum metabolites were associated with postoperative opioid consumption. Different efficiencies of histamine degradation may be one cause of the variable sensitivity of patients to acute pain and warrants further study.
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March 2022

Severe pre-operative sinus bradycardia improved by mediastinal lymph node dissection.

BMC Surg 2022 Mar 22;22(1):107. Epub 2022 Mar 22.

Department of Anesthesiology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, 100142, China.

Background: We report a case of bradycardia improved by surgical resection of the paratracheal lymph nodes, which has rarely been reported in the literature.

Case Presentation: A 41-year-old male patient with pre-operative sinus bradycardia was diagnosed with right upper lobe adenocarcinoma. He planned to undergo VATS right upper lobectomy and mediastinal lymph node dissection. Consultation indicated that there was no need to place a temporary pacemaker. Severe sinus bradycardia occurred during induction of anesthesia and heart rate (HR) fell significantly from 52 to 28 bpm. There was no response to atropine. Isoproterenol was administered continuously for two hours at 0.01 µg per kg per minute to keep the patient's HR around 50 bpm. During the operation, it was noted that the right upper mediastinal lymph nodes (group R2 and R4) were calcified and very close to the vagus nerve. After resection of the lymph nodes, the patient's HR returned to 60-68 bpm without isoproterenol. There were no post-operative complications and the patient was discharged on the 5th post-operative day. The pathological findings indicated invasive adenocarcinoma with no lymph node metastases. One month after surgery, 24-h Holter monitoring revealed sinus rhythm without bradycardia. Six months after surgery no sinus bradycardia has occurred thus far.

Conclusions: Patients with persistent sinus bradycardia pre-operation caused by vagus nerve compression deserve attention. Guidelines on placement of temporary pacemakers and intraoperative anesthesia management may be improved by additional clinical experience.
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http://dx.doi.org/10.1186/s12893-022-01547-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8939192PMC
March 2022

FGF4, A New Potential Regulator in Gestational Diabetes Mellitus.

Front Pharmacol 2022 4;13:827617. Epub 2022 Mar 4.

Department of Infectious Diseases & Zhejiang Provincial Key laboratory of Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Gestational diabetes mellitus (GDM) is associated with adverse maternal and neonatal outcomes, however the underlying mechanisms remain elusive. The aim of this study was to find efficient regulator of FGFs in response to the pathogenesis of GDM and explore the role of the FGFs in GDM. We performed a systematic screening of placental FGFs in GDM patients and further in two different GDM mouse models to investigate their expression changes. Significant changed FGF4 was selected, engineered, purified, and used to treat GDM mice in order to examine whether it can regulate the adverse metabolic phenotypes of the diabetic mice and protect their fetus. We found FGF4 expression was elevated in GDM patients and its level was positively correlated to blood glucose, indicating a physiological relevance of FGF4 with respect to the development of GDM. Recombinant FGF4 (rFGF4) treatment could effectively normalize the adverse metabolic phenotypes in high fat diet induced GDM mice but not in STZ induced GDM mice. However, rFGF4 was highly effective in reduce of neural tube defects (NTDs) of embryos in both the two GDM models. Mechanistically, rFGF4 treatment inhibits pro-inflammatory signaling cascades and neuroepithelial cell apoptosis of both GDM models, which was independent of glucose regulation. Our study provides novel insight into the important roles of placental FGF4 and suggests that it may serve as a promising diagnostic factor and therapeutic target for GDM.
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http://dx.doi.org/10.3389/fphar.2022.827617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8934430PMC
March 2022

Polymeric coating lubricates nanocontainers to escape macrophage uptake for bioreceptor recognition.

Bioact Mater 2022 Aug 4;14:120-133. Epub 2022 Jan 4.

State Key Laboratory of Tribology, Department of Mechanical Engineering, Tsinghua University, Beijing, 100084, China.

Accurate drug delivery to the lesion has been deliberated for several decades, but one important phenomenon is usually neglected that the immune system can prevent smooth transportation of nanomedicine. Although injection would reduce first-pass effect, macrophages in the blood can still recognize and phagocytose nanomedicine. Here we show that a lubricated nanocontainer, which is prepared based on polyelectrolytes and mesoporous silica nanoparticles, can accurately target muscarinic bioreceptor while escaping from the identification of macrophages. Through and studies, this nanocontainer, combining both immune escape and bioreceptor targeting, has greatly improved the drug bioavailability. Additionally, this nanocontainer shows good biocompatibility, and the targeted heart tissues and other important metabolic organs, such as liver and kidney, keep physiological structures and functions without the detection of side effects. Furthermore, the mechanism of immune escape for the developed nanocontainer has been investigated by lubrication test and molecular simulation. We anticipate that our study will establish a new perspective on the achievement of immune escape-based targeted drug delivery, which can provide a fundamental approach for the design of related biomaterials.
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http://dx.doi.org/10.1016/j.bioactmat.2021.12.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8892157PMC
August 2022

Induction of Apoptosis by Metabolites of Rhei Radix et Rhizoma (Da Huang): A Review of the Potential Mechanism in Hepatocellular Carcinoma.

Front Pharmacol 2022 2;13:806175. Epub 2022 Mar 2.

Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Liver cancer is a global disease with a high mortality rate and limited treatment options. Alternations in apoptosis of tumor cells and immune cells have become an important method for detailing the underlying mechanisms of hepatocellular carcinoma (HCC). Bcl-2 family, Caspase family, Fas and other apoptosis-related proteins have also become antagonistic targets of HCC. Da Huang (Rhei Radix et Rhizoma, RR), a traditional Chinese herb, has recently demonstrated antitumor behaviors. Multiple active metabolites of RR, including emodin, rhein, physcion, aloe-emodin, gallic acid, and resveratrol, can successfully induce apoptosis and inhibit HCC. However, the underlying mechanisms of these metabolites inhibiting the occurrence and development of HCC by inducing apoptosis is complicated owing to the multi-target and multi-pathway characteristics of traditional Chinese herbs. Accordingly, this article reviews the pathways of apoptosis, the relationship between HCC and apoptosis, the role and mechanism of apoptosis induced by mitochondrial endoplasmic reticulum pathway and death receptor pathway in HCC and the mechanism of six RR metabolites inhibiting HCC by inducing apoptosis.
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http://dx.doi.org/10.3389/fphar.2022.806175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8924367PMC
March 2022

Formononetin attenuates Aβ-induced adhesion molecules in HBMECs via Nrf2 activation.

Brain Res Bull 2022 06 15;183:162-171. Epub 2022 Mar 15.

Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei, PR China. Electronic address:

Brain vascular inflammation plays a crucial role in the pathogenesis of Alzheimer's disease (AD). As a central pathogenic factor in AD, the extracellular buildup of amyloid-β (Aβ) induces brain microvascular endothelial cells activation, impairs endothelial structure and function. Formononetin (FMN) has been reported to protect against Alzheimer's disease (AD) and attenuates vascular inflammation in atherosclerosis. However, its involvement in regulating vascular inflammation of AD has not been investigated. In the study, we found that FMN significantly attenuates Aβ-induced expression of adhesion molecules, including intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the human brain microvascular endothelial cells (HBMECs), suggesting that FMN inhibits Aβ-induced brain endothelial cells inflammatory response. Moreover, we observed that FMN attenuates Aβ-induced translocation of NFκB (p65) into the nucleus of HBMECs, and found that FMN treatment induces Nrf2 expression and attenuates Nrf2-Keap1 association in a dose-dependent manner in HBMECs. Furthermore, we demonstrated that Nrf2 silencing significantly attenuates FMN-reduced NFκB (p65) activation and nuclear translocation. Lastly, our results showed that FMN treatment attenuates Aβ-induced adhesion of THP-1 cell to endothelial cell monolayer. Collectively, these findings suggest that FMN attenuates Aβ-induced activation in human brain microvascular endothelial cells, which at least in part was mediated through Nrf2 pathways.
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http://dx.doi.org/10.1016/j.brainresbull.2022.03.009DOI Listing
June 2022

Multi-constraint Gerchberg-Saxton iteration algorithms for linearizing IM/DD transmission systems.

Opt Express 2022 Mar;30(6):10019-10031

Chromatic dispersion-enhanced signal-signal beating interference (SSBI) considerably affects the performance of intensity-modulation and direct-detection (IM/DD) fiber transmission systems. For recovering optical fields from received double sideband signals after propagating through IM/DD transmission systems, Gerchberg-Saxton (G-S) iterative algorithms are promising, which, however, suffers slow convergence speeds and local optimization problems. In this paper, we propose a multi-constraint iterative algorithm (MCIA) to extend the Gerchberg-Saxton-based linearized detection. The proposed technique can accelerate the convergence speed and realize nonlinear-equalization-free detection. Based on the data-aided iterative algorithm (DIA) and the decision-directed data-aided iterative algorithm (DD-DIA), the proposed technique reuses redundant bits from channel coding to not only correct decision errors but also enforce the constraints on the task function to further accelerate the whole optical field retrieval processing. Simulation results show that, compared with the DD-DIA, the MCIA reduces the received optical power (ROP) by about 1.5-dB for a 100-Gb/s over 50-km SSMF PAM-4 signal transmission at the symbol error rate (SER) of 2×10. For a 100-Gb/s over 400-km SSMF transmission system, just 30 MCIA iterations is needed, which is 30% reduction in iteration count compared with the DD-DIA. For further increased transmission capacities, the MCIA can improve the SER by two orders of magnitude compared with the conventional IA. To validate the effectiveness of the MCIA, we also conduct experiments to transmit 92-Gb/s PAM-4 signals over 50-km IM/DD fibre systems. We find that the MCIA has a 1-dB ROP improvement compared with the DD-DIA. Compared with Volterra nonlinear equalization, the BERs of the MCIA with a simple linear equalizer are reduced by more than one order of magnitude with only 52 MCIA iterations.
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http://dx.doi.org/10.1364/OE.448826DOI Listing
March 2022
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