Publications by authors named "Hang Wang"

459 Publications

The covalent Coordination-driven [email protected](Ti)-SH heterojunction with boosting photocatalytic CO reduction and dye degradation performance.

J Colloid Interface Sci 2021 Aug 28;606(Pt 2):1745-1757. Epub 2021 Aug 28.

School of Materials Science and Engineering, Shanghai Institute of Technology, Shanghai 201418, China. Electronic address:

Herein, the optional and controllable growth of BiS onto NH-MIL-125 via covalent conjunction strategy was reported. The experimental results demonstrate that the obtained heterojunction exhibits boosting photocatalytic reduction CO and organic dye degradation. The [email protected] displays the highest yield of 12.46 μmol gh of CO, >13 times that of pure NH-MIL-125. Meanwhile, the reaction kinetic of [email protected] in the degradation of methylene blue is uppermost, which is 160 times than that of the commercial P25. The enhancement of photocatalytic performance could be ascribed to the covalent coordination-driven intimate interfacial interaction in n-scheme heterojunction. Meanwhile, the plausible mechanism was also investigated by UV-vis diffuse reflectance (UV-vis), photoluminescence (PL), electrochemical photocurrent, electron spin resonance (ESR) and electrochemical impedance spectroscopy (EIS).
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http://dx.doi.org/10.1016/j.jcis.2021.08.135DOI Listing
August 2021

Exosomal Noncoding RNAs in Hepatobiliary Cancer: A Rising Star.

Mol Cancer Ther 2021 Aug 10. Epub 2021 Aug 10.

Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Hepatobiliary cancers are a heterogeneous group of malignancies with a dismal prognosis. Despite intensive research efforts focused on these tumors, methods for early diagnosis and effective targeted therapies are still lacking. Exosomes, released by most cells, exist in all kinds of body fluids and play an important role in cell-to-cell communication. They are small membranous vesicles containing biological molecules, such as noncoding RNAs (ncRNA), which are not translated into proteins, but they exert effects on the regulation of gene transcription and translation. There is growing evidence for the essential roles of ncRNAs in exosomes in both physiologic and pathologic conditions of hepatobiliary cancers. They have been identified as sensitive diagnostic biomarkers as well as potential therapeutic targets. The present review discusses recent findings in the cross-talk between hepatobiliary cancers cells and the surrounding cells of the microenvironment and discuss their potential clinical usage.
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http://dx.doi.org/10.1158/1535-7163.MCT-21-0363DOI Listing
August 2021

The preoperative prognostic value of the radiomics nomogram based on CT combined with machine learning in patients with intrahepatic cholangiocarcinoma.

World J Surg Oncol 2021 Aug 1;19(1):45. Epub 2021 Aug 1.

Department of Biotherapy, West China Hospital and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu, 610041, People's Republic of China.

Background: Intrahepatic cholangiocarcinoma is an aggressive liver carcinoma with increasing incidence and mortality. A good auxiliary prognostic prediction tool is desperately needed for the development of treatment strategies. The purpose of this study was to explore the prognostic value of the radiomics nomogram based on enhanced CT in intrahepatic cholangiocarcinoma.

Methods: In this retrospective study, 101 patients with pathological confirmation of intrahepatic cholangiocarcinoma were recruited. A radiomics nomogram was developed by radiomics score and independent clinical risk factors selecting from multivariate Cox regression. All patients were stratified as high risk and low risk by a nomogram. Model performance and clinical usefulness were assessed by calibration curve, ROC curve, and survival curve.

Results: A total of 101patients (mean age, 58.2 years old; range 36-79 years old) were included in the study. The 1-year, 3-year, and 5-year overall survival rates were 49.5%, 26.6%, and 14.4%, respectively, with a median survival time of 12.2 months in the whole set. The least absolute shrinkage and selection operator (LASSO) method selected 3 features. Multivariate Cox analysis found three independent prognostic factors. The radiomics nomogram showed a significant prognosis value with overall survival. There was a significant difference in the 1-year and 3-year survival rates of stratified high-risk and low-risk patients in the whole set (30.4% vs. 56.4% and 13.0% vs. 30.6%, respectively, p = 0.018).

Conclusions: This radiomics nomogram has potential application value in the preoperative prognostic prediction of intrahepatic cholangiocarcinoma and may facilitate in clinical decision-making.
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http://dx.doi.org/10.1186/s12957-021-02162-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327418PMC
August 2021

Meta-analysis of cryoballoon ablation versus antiarrhythmic drugs as initial therapy for symptomatic atrial fibrillation.

Clin Cardiol 2021 Jul 29. Epub 2021 Jul 29.

Department of Pharmacy, First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

Background: The optimal first-line approach for patients with symptomatic atrial fibrillation (AF) remains unclear. We compared the efficacy and safety of cryoballoon ablation (CBA) and antiarrhythmic drugs (AADs) in the initial management of symptomatic AF.

Hypothesis: CBA is superior to AAD as initial therapy for symptomatic AF.

Methods: We searched the EMBASE, PubMed, and Cochrane Library databases for randomized controlled trials (RCTs) that compared CBA with AAD as first-line treatment for AF from the date of database establishment until March 18, 2021. The risk ratio (RR) with a 95% confidence interval (CI) was used as a measure of treatment effect.

Results: Three RCTs that enrolled 724 patients in total were included in this meta-analysis. Majority of the patients were relatively young and had paroxysmal AF. CBA was associated with a significant reduction in the recurrence of atrial arrhythmia compared with AAD therapy, with low heterogeneity (RR, 0.59; 95% CI, 0.49-0.71; p < .00001; I  = 0%). There was a significant difference in the rate of symptomatic atrial arrhythmia recurrence (RR, 0.44; 95% CI, 0.29-0.65; p < .0001; I  = 0%); however, the rate of serious adverse events was similar between the two treatment groups (RR: 1.18; 95% CI: 0.71-1.97, p = .53; I  = 0%). Transient phrenic nerve palsy occurred in four patients after the CBA procedure.

Conclusion: The current meta-analysis suggests that CBA is more effective than AAD as initial therapy in patients with symptomatic paroxysmal AF. Serious iatrogenic adverse events are uncommon in CBAs.
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http://dx.doi.org/10.1002/clc.23695DOI Listing
July 2021

Genome Size Estimation and Full-Length Transcriptome of : Genetic Background of a Drought-Adapted Grasshopper.

Front Genet 2021 12;12:678625. Epub 2021 Jul 12.

College of Life Sciences, Shaanxi Normal University, Xi'an, China.

Fieber, 1852 (Orthoptera: Acrididae), is a grasshopper genus comprising approximately 170 species, all of which prefer dry environments such as deserts, steppes, and stony benchlands. In this study, we aimed to examine the adaptation of grasshopper species to arid environments. The genome size of was estimated using flow cytometry, and the first high-quality full-length transcriptome of this species was produced. The genome size of is approximately 12.8 Gb. Based on 146.98 Gb of PacBio sequencing data, 221.47 Mb full-length transcripts were assembled. Among these, 88,693 non-redundant isoforms were identified with an N50 value of 2,726 bp, which was markedly longer than previous grasshopper transcriptome assemblies. In total, 48,502 protein-coding sequences were identified, and 37,569 were annotated using public gene function databases. Moreover, 36,488 simple tandem repeats, 12,765 long non-coding RNAs, and 414 transcription factors were identified. According to gene functions, 61 cytochrome P450 (CYP450) and 66 heat shock protein (HSP) genes, which may be associated with drought adaptation of , were identified. We compared the transcriptomes of and two other grasshopper species which were less tolerant to drought, namely and . We observed the expression of CYP450 and HSP genes in were higher. We produced the first full-length transcriptome of a species that has an ultra-large genome. The assembly characteristics were better than those of all known grasshopper transcriptomes. This full-length transcriptome may thus be used to understand the genetic background and evolution of grasshoppers.
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http://dx.doi.org/10.3389/fgene.2021.678625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313316PMC
July 2021

No Detection of Pseudocapsule of Tumor-Parenchyma Interface on Multidetector Computed Tomography (MDCT) Images: Clinical Significance and Histological Reflections in Renal Cell Carcinoma.

Cancer Manag Res 2021 6;13:5403-5411. Epub 2021 Jul 6.

Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China.

Objective: Pseudocapsule (PS) of tumor-parenchyma interface (TPI) can be detected by MDCT (ctPS) in renal cell carcinoma (RCC) with exceptions. We aim to study the prognostic implications and histological reflections of no detection of ctPS in RCC.

Patients And Methods: A total of 210 RCC patients who had MDCT examination and received nephrectomy in our institution were included in the analysis. Absence or presence of ctPS was recognized, and its associations with overall survival (OS) and progression-free survival (PFS), pathological PS (pPS) and vasculature were studied.

Results: A total of 172 (81.9%) patients were recognized to have a ctPS and 38 (18.1%) had no detection of it. They had comparable histology, stage, grade, and necrosis. Patients without a ctPS had significantly shortened overall survival (OS, p = 0.001) and progression-free survival (PFS, p <0.001), the significance of which persisted in multivariable analysis (OS, HR 3.104, p = 0.003; PFS, HR 3.313, p = 0.001). Nearly all tumors (34/38, 89.4%) without a ctPS actually had a pPS being detected and incompleteness of pPS was also irrelevant (p = 0.739). Compared with ctPS presence, those without a ctPS had significantly thinned pPS (0.36 vs 0.43 mm, p = 0.005). In clear-cell histology, those without a ctPS also contained increased vascular density and cross-sectional area of vessels with long diameter ≥200 um in the pPS layer (p = 0.005 and 0.011) and increased vascular density in the 500 um layer outside pPS (p = 0.017).

Conclusion: Absence of ctPS on MDCT significantly increases the risk of adverse clinical outcome in RCC. It is the reflection of a thinner pPS and enriched vasculature of TPI rather than absence of pPS itself.
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http://dx.doi.org/10.2147/CMAR.S315379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275039PMC
July 2021

[Urine metabolomics analysis based on ultra performance liquid chromatography-high resolution mass spectrometry combined with osmolality calibration sample concentration variability].

Se Pu 2021 Apr;39(4):391-398

School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.

Urine is an important source of biomolecular information for metabolomic studies. However, the acquisition of high-quality metabolomic datasets or reliable biomarkers from urine is difficult owing to the large variations in the concentrations of endogenous metabolites in the biofluid, which are caused by diverse factors such as water consumption, drugs, and diseases. Thus, normalization or calibration is essential in urine metabolomics for eliminating such deviations. The urine osmolality (), which is a direct measure of the total urinary solute concentration and is not affected by circadian rhythms, diet, gender, and age, is often considered the gold standard for estimation of the urine concentration. In this study, a pre-data acquisition calibration strategy based on osmolality was investigated for its feasibility to overcome sample concentration variability. Before data acquisition, the product of the osmolality×injection volume of all samples was set to be equivalent through the uses of a customized injection volume or dilution. After ultra performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) analysis of the sample, the raw dataset was normalized to the total ion abundance or total useful MS signals (MSTUS) to achieve further calibration. The osmolality of each urine sample was determined with a freezing-point depression osmometer. For the instrumental analysis, a Vanquish UPLC system coupled to a Q-Exactive Plus HRMS device was used for metabolite analysis and accurate mass measurement. Full-scan mass spectra were acquired in the range of 60-900, and the MS/MS experiments were conducted in "Top5" data-dependent mode. A Waters UPLC column (100 mm×2.1 mm, 1.8 μm) was used for chromatography separation. The raw data were imported into Progenesis QI software for peak picking, alignment, deconvolution, and normalization. SIMCA-P software was used for the principal component analysis (PCA) and orthogonal partial least-squares discrimination analysis (OPLS-DA). This strategy was first applied to sequentially diluted urine samples, where three frequently used normalization methods were compared. In the identical injection volume experiment, the points were scattered and showed relevant distribution according to the dilution multiple in the plot of PCA scores. There was little improvement after normalization to either the total ion abundance or MSTUS. In the customized injection volume experiment, the urine samples derived from the same source showed ideal clustering. With total ion abundance and MSTUS normalization, the dataset was further improved in the PCA model fitting and prediction. As a result, there were more peaks with a peak area RSD of <30%, which indicated better parallelism. The diluted urine solutions had higher Spearman's coefficient values with their sample source than those without calibration, which suggested less intra-group differences. The strategy was further validated using data from a metabolomic study of children with congenital hydronephrosis and healthy controls. As a concentration estimator, osmolality showed better linear correlation with the mass signal and was less influenced by physiological or pathological factors, thus obtaining broader application and more accurate results than creatinine. The concentration variability was effectively eliminated after customized dilution calibration and showed a more obvious clustering effect in the PCA score plot. The OPLS-DA-based statistical model used to identify discriminate metabolites was improved, with less chance of overfitting. In conclusion, the calibration strategy based on osmolality combined with total ion abundance or MSTUS normalization significantly overcame the problem of urine concentration variability, eliminated intra-group differences, and possessed better parallelism, thus giving better clustering effects in PCA or OPLS-DA and higher reliability of the statistical model. The results of this study provide guidance and a reference for future metabolomic studies on urine.
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http://dx.doi.org/10.3724/SP.J.1123.2020.06018DOI Listing
April 2021

Treatment of Acute Pain in Adults With Sickle Cell Disease in an Infusion Center Versus the Emergency Department : A Multicenter Prospective Cohort Study.

Ann Intern Med 2021 Jul 6. Epub 2021 Jul 6.

Oncology Biostatistics and Bioinformatics, Johns Hopkins University, Baltimore, Maryland (R.V.).

Background: Patients with sickle cell disease (SCD) have vaso-occlusive crises (VOCs). Infusion centers (ICs) are alternatives to emergency department (ED) care and may improve patient outcomes.

Objective: To assess whether care in ICs or EDs leads to better outcomes for the treatment of uncomplicated VOCs.

Design: Prospective cohort. (ClinicalTrials.gov: NCT02411396).

Setting: 4 U.S. sites, with recruitment between April 2015 and December 2016.

Participants: Adults with SCD living within 60 miles of a study site.

Measurements: Participants were followed for 18 months after enrollment. Outcomes of interest were time to first dose of parenteral pain medication, whether pain reassessment was completed within 30 minutes after the first dose, and patient disposition on discharge from the acute care visit. Treatment effects for ICs versus EDs were estimated using a time-varying propensity score adjustment.

Results: Researchers enrolled 483 participants; the 269 who had acute care visits on weekdays are included in this report. With inverse probability of treatment-weighted adjustment, the mean time to first dose was 62 minutes in ICs and 132 minutes in EDs; the difference was 70 minutes (95% CI, 54 to 98 minutes; E-value, 2.8). The probability of pain reassessment within 30 minutes of the first dose of parenteral pain medication was 3.8 times greater (CI, 2.63 to 5.64 times greater; E-value, 4.7) in the IC than the ED. The probability that a participant's visit would end in admission to the hospital was smaller by a factor of 4 (0.25 [CI, 0.18 to 0.33]) with treatment in an IC versus an ED.

Limitation: The study was restricted to participants with uncomplicated VOCs.

Conclusion: In adults with SCD having a VOC, treatment in an IC is associated with substantially better outcomes than treatment in an ED.

Primary Funding Source: Patient-Centered Outcomes Research Institute.
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http://dx.doi.org/10.7326/M20-7171DOI Listing
July 2021

Discovery of a Fluorogenic Probe for In Situ Pyruvate Kinase M2 Isoform (PKM2) Labeling through Chemoselective SAr with a Binding Site Lysine Residue.

Anal Chem 2021 07 5;93(28):9669-9676. Epub 2021 Jul 5.

State Key Laboratory of Fine Chemicals, Zhang Dayu School of Chemistry, Dalian University of Technology, Dalian, Liaoning 116024, China.

The key challenge of developing reaction-based turn-on probes is to establish latent electrophilic fluorophores exhibiting high reactivity only upon binding to a specific protein(s). Herein, we identified such a fluorophore, 6-arylthioether-substituted 3-cyano-1-oxo-1-phenalene-2-carboxylate, which chemoselectively labels binding site Cys or Lys residues. Based on this fluorophore, we developed the first reaction-based turn-on pyruvate kinase M2 isoform (PKM2) fluorescent probe , which selectively labels PKM2 with the binding site Lys305. The latent electrophilic reactivity of the fluorophore endows the probe with precise detection of the expression of PKM2 in situ by means of both in-gel fluorescence imaging at the proteome level and real-time no-wash cell imaging approaches, which has the potential to be applied in cancer diagnoses.
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http://dx.doi.org/10.1021/acs.analchem.1c00208DOI Listing
July 2021

Real-time assessment of global and regional lung ventilation in the anti-gravity straining maneuver using electrical impedance tomography.

Comput Biol Med 2021 08 21;135:104592. Epub 2021 Jun 21.

Department of Biomedical Engineering, Fourth Military Medical University, Xi'an, China; Institute of Technical Medicine, Furtwangen University, Villingen-Schwenningen, Germany. Electronic address:

Objective: Anti-gravity straining maneuver (AGSM) helps to reduce the occurrence of gravity-induced visual disturbances and loss of consciousness. An objective assessment of the AGSM is still missing during ground training. This study evaluated the feasibility of using electrical impedance tomography (EIT) to assess the performance of AGSM.

Methods: Eight undergraduates and eight teachers majoring in aerospace medicine were included in the study. An experienced professor from the department of aerospace medicine reviewed the key points of AGSM with each subject. EIT measurement was performed during AGSM. The global and regional ventilation were used to investigate the characteristics of AGSM. The professor and the subjects rated the performance of AGSM according to the maneuver requirements of AGSM (maximum 16 points) before and after reviewing the ventilations from EIT.

Results: For global ventilation, the relative depth of gas exchange and duration of exhalation of the teachers were larger than those of the students (p < 0.01), and stability of the teachers was better as well (p < 0.001). No difference in the duration of gas exchange and leakage during exhalation between the teachers and the students was found. For regional ventilation, the teachers had significantly increased ventral ventilation during AGSM implementation (p < 0.001) whereas students did otherwise. Additionally, the differences of rating scores with and without EIT were also significant. Significant reductions were found in rating scores with EIT assessed by the professor (4.5 ± 2.0, p < 0.001) and by the students themselves (3.9 ± 2.2, p < 0.001). The scores were systematically higher when the students rated themselves compared with the professor's rating (p < 0.001 for both with and without EIT).

Conclusion: These findings demonstrated that EIT could objectively characterize the maneuver details of AGSM, which might provide a potential tool for real-time assessment of AGSM quality in an objective manner.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104592DOI Listing
August 2021

[Effects of plant community and soil properties on soil bacterial community in Bitahai Wetland, Southwest China].

Ying Yong Sheng Tai Xue Bao 2021 Jun;32(6):2199-2208

Faculty of Wetland, Southwest Forestry University, Kunming 650224, China.

Soil microorganism was the engine of the migration and transformation of biological elements in the soil-plant system of wetland ecosystems. Exploring the relationship between plant community, soil properties, and spatial structure with soil microorganisms is the key to maintain the health and stability of wetlands. In order to examine the effects of plant community, soil properties, and spatial structure on the bacterial community in wetlands, we used two-way indicator species analysis (TWINSPAN) to classify plant communities from 35 samples collected in Bitahai Wetland. We measured microbial community composition at the surface soil of the samples using high-throughput sequencing technology, and analyzed the relationship among plant community, soil pro-perties and spatial structure with bacterial community. The results showed that plant communities could classified into three different types by TWINSPAN. The physiognomy and structure of plant communities in same community type were relatively consistent. We found that quantitative classification had good applicability in vegetation classification of plateau wetland ecosystem. Acidobacteriota (21.0%), Chloroflexi (15.5%), Proteobacteria (15.3%) and Bacteroidetes (10.1%) had higher population densities (≥10%) in Bitahai Wetland. Analysis of similarities (ANOSIM) showed that different plant community types differed significantly in bacterial community composition, suggesting that plant communities could affect bacterial community. Cano-nical correspondence analysis (CCA) results showed that plant diversity, soil water content (SWC), pH, iron (Fe) and spatial structure were the dominated factors that significantly affecting bacterial community. The variance partitioning analysis (VPA) results showed that bacterial community was affected by single environment factors and their interactions. Our results highlighted that bacterial community is shaped by plant community, soil properties and spatial structure, with their effects being indivisible.
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http://dx.doi.org/10.13287/j.1001-9332.202106.039DOI Listing
June 2021

Apigenin inhibits the growth of colorectal cancer through down-regulation of E2F1/3 by miRNA-215-5p.

Phytomedicine 2021 Aug 24;89:153603. Epub 2021 May 24.

West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China. Electronic address:

Background: Apigenin (API) is a naturally occurring plant-derived flavone, which is abundantly present in common fruits and vegetables, and shows little or no toxicity of daily diet. The treatment of colorectal cancer is limited by high recurrence rate and multidrug resistance.

Purpose: The purpose of this study was to explore the potential therapeutic effect and possible mechanisms of API on colorectal cancer cells.

Methods: Cell proliferation and apoptosis of human colon cancer cell line HCT116 was assessed after API treatment. A comprehensive transcriptome profile of API-treated HCT116 cells was acquired by high-throughput sequencing. The regulation of miRNA215-5p and E2F1/3 were identified by bioinformatics analyses. An inhibitor of miRNA215-5p, inhibitor 215, was applied to confirm the role of this microRNA played in the anti-cancer effect of API. Luciferase reporter gene assay was performed to identify targeting relationship between miRNA215-5p and E2F1/3.

Result: API significantly promoted cell apoptosis and anti-proliferation of HCT116 cells in a dose-dependent manner. Bioinformatics analyses identified several altered miRNAs among which the expression of miRNA-215-5p showed markedly increased. Meanwhile, the expression of E2F1 and E2F3 was decreased by API, which was associated with miRNA215-5p. Luciferase reporter gene assay showed miRNA-215-5p could directly bind to 3' UTR of E2F1/3. Inhibition of miRNA-215-5p significantly inhibited apoptosis and cell cycle arrest at G0/G1 phase induced by API.

Conclusions: The result of this study confirmed the anti-cancer effect of API on human colorectal cancer cells and investigated the underlying mechanism by a comprehensive transcriptome profile of API-treated cells.
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http://dx.doi.org/10.1016/j.phymed.2021.153603DOI Listing
August 2021

Galactosylation of rhamnogalacturonan-II for cell wall pectin biosynthesis is critical for root apoplastic iron reallocation in Arabidopsis.

Mol Plant 2021 Jun 23. Epub 2021 Jun 23.

National Key Laboratory of Plant Molecular Genetics, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200032, China; University of Chinese Academy of Sciences, Beijing 100049, China; School of Life Science and Technology, Shanghai Tech University, Shanghai 201210, China. Electronic address:

Apoplastic iron (Fe) in roots represents an essential Fe storage pool. Reallocation of apoplastic Fe is of great importance to plants experiencing Fe deprivation, but how this reallocation process is regulated remains elusive, likely because of the highly complex cell wall structure and the limited knowledge about cell wall biosynthesis and modulation. Here, we present genetic and biochemical evidence to demonstrate that the Cdi-mediated galactosylation of rhamnogalacturonan-II (RG-II) is required for apoplastic Fe reallocation. Cdi is expressed in roots and up-regulated in response to Fe deficiency. It encodes a putative glycosyltransferase localized to the Golgi apparatus. Biochemical and mass spectrometry assays showed that Cdi catalyzes the transfer of GDP-L-galactose to the terminus of side chain A on RG-II. Disruption of Cdi essentially decreased RG-II dimerization and hence disrupted cell wall formation, as well as the reallocation of apoplastic Fe from roots to shoots. Further transcriptomic, Fourier transform infrared spectroscopy, and Fe desorption kinetic analyses coincidently suggested that Cdi mediates apoplastic Fe reallocation through extensive modulation of cell wall components and consequently the Fe adsorption capacity of the cell wall. Our study provides direct evidence demonstrating a link between cell wall biosynthesis and apoplastic Fe reallocation, thus indicating that the structure of the cell wall is important for efficient usage of the cell wall Fe pool.
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http://dx.doi.org/10.1016/j.molp.2021.06.016DOI Listing
June 2021

Correction to: CDK4/6 inhibition blocks cancer metastasis through a USP51-ZEB1-dependent deubiquitination mechanism.

Signal Transduct Target Ther 2020 Jun 19;5(1):103. Epub 2020 Jun 19.

Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Medical College of Nankai University, Tianjin, 300071, China.

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http://dx.doi.org/10.1038/s41392-020-00212-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305231PMC
June 2020

Effects of macrophage regulation on fat grafting survival: Improvement, mechanisms, and potential application-A review.

J Cosmet Dermatol 2021 Jun 15. Epub 2021 Jun 15.

State Key Laboratory of Oral Diseases, Department of Cosmetic and Plastic Surgery, Oral and Maxillofacial Surgery, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Background: Autologous fat grafting has become a popular tool in plastic surgery to solve soft tissue defects and achieve skin rejuvenation, but the volume loss after transplantation remains a disturbing problem. In recent years, some new strategies have improved the outcome to some extent, but the fat graft retention is still far from ideal, so there remains a wide development prospect in this field. Macrophages are closely related to the local microenvironment and tissue regeneration, and their role in fat grafting has been increasingly highlighted.

Aims: This article was aimed to review the efficacy, possible mechanisms, and potential application of macrophage regulation on fat grafting, as well as concerns and future perspectives of this filed.

Methods: A retrospective review of the published data was conducted.

Results: Most studies indicated that up-regulating M2 macrophages during fat grafting would improve fat retention via promoting neovascularization. M2 macrophages could secrete several pro-angiogenic factors, accelerate extracellular matrix (ECM) remodeling, and directly function on endothelial cells to encourage vascular expansion. In addition, macrophages could influence the proliferation, apoptosis, and adipogenic differentiation of preadipocytes.

Conclusions: During autologous fat grafting, appropriately regulating macrophages may become a promising method to increase fat retention. Nevertheless, the M2 macrophage polarizing agents, treatment opportunity, and contraindications require further discussion. We hope our work could promote more in-depth studies in this field, and we are looking forward to a standard procedure for the macrophage therapy in clinical practice.
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http://dx.doi.org/10.1111/jocd.14295DOI Listing
June 2021

Physicochemical properties, digestibility and anti-osteoporosis effect of yak bone powder with different particle sizes.

Food Res Int 2021 07 11;145:110401. Epub 2021 May 11.

Key Laboratory of Agro-Products Processing, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China. Electronic address:

As a kind of promising resource, animal bone has been widely processed into functional foods. However, there is little research about the effect of particle size on the physicochemical properties and digestibility of yak bone powder (YBP), as well as its anti-osteoporosis activity. In this study, the YBP with median particle sizes (MPS) ranging from 19.68 to 128.37 μm were prepared, and their digestibility and anti-osteoporosis activity were investigated. The results showed that smaller MPS significantly increased water holding capacity and protein solubility without changing composition. The MPS reduction greatly promoted protein digestion, producing more peptides<3 kDa and free amino acids while decreased Ca and P release during gastrointestinal digestion. The in vivo results revealed the positive effect of YBP on ovariectomy-induced osteoporosis in rats. The bone mineral density of ovariectomized (OVX) rats was obviously improved by regulating bone turnover markers (B-ALP, OCN, S-CTX, ES and TRAP), thus potentially shedding light on osteoporosis remission. However, different MPS exhibited a weak effect on osteoporosis in OVX rats. Therefore, YBP could be produced in relatively large particle size without sacrificing food sensory quality, the processing time of which could also be shortened for higher productivity and lower cost.
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http://dx.doi.org/10.1016/j.foodres.2021.110401DOI Listing
July 2021

Association between PM and specific circulatory system diseases in China.

Sci Rep 2021 Jun 9;11(1):12129. Epub 2021 Jun 9.

Key Laboratory of Semi-Arid Climate Change, College of Atmospheric Sciences, Ministry of Education, Lanzhou University, Lanzhou, 730000, China.

Particulate matter (PM) has been proved to be a risk factor for the development of circulatory system diseases (CSDs) around the world. In this study, we collected daily air pollutants, emergency room (ER) visits for CSDs, and meteorological data from 2009 to 2012 in Beijing, China. After controlling for the long-term trend and eliminating the influence of confounding factors, the generalized additive model (GAM) was used to evaluate the short-term effects of PM on CSDs and cause-specific diseases. The results showed that for every 10 μg/m increase in PM, the largest effect estimates in ER visits of total CSDs, arrhythmia, cerebrovascular diseases, high blood pressure, ischemic heart disease and other related diseases were 0.14% (95% CI: 0.06-0.23%), 0.37% (95% CI: - 0.23 to 0.97%), 0.20% (95% CI: 0.00-0.40%), 0.15% (95% CI: 0.02-0.27%), 0.18% (95% CI: 0.02-0.35%) and 0.35% (95% CI: - 0.04 to 0.79%), respectively. When NO or SO was added into the model, the effect estimates of PM were mostly attenuated, while in those models with PM added, the effect estimates of PM were mostly increased. Stratified analysis indicated that PM had a greater effect on males and the elderly.
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http://dx.doi.org/10.1038/s41598-021-91637-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190074PMC
June 2021

An illustrated key to the species of Latreille (Hymenoptera, Gasteruptiidae) from Palaearctic China, with description of four new species.

Zookeys 2021 19;1038:1-103. Epub 2021 May 19.

Shaanxi Key Laboratory for Animal Conservation / Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China Northwest University Xi'an China.

Four new species of the genus Latreille, 1797 (Hymenoptera: Evanioidea: Gasteruptiidae: Gasteruptiinae) are described from China. Three are from Shaanxi (NW China; Tan & van Achterberg, , Tan & van Achterberg, , and Tan & van Achterberg, ) and one from S China and Ningxia ( Tan & van Achterberg, ). Eleven species are newly recorded for Shaanxi ( Kieffer, 1912, Pasteels, 1958, Pasteels, 1958, Enderlein, 1913, Zhao, van Achterberg & Xu, 2012, (Tournier, 1877), (Thomson, 1883), Enderlein, 1913, Kieffer, 1911, (Thomson, 1883) and Kieffer, 1911). The newly-recorded species and the new species are keyed and illustrated. Two new synonyms are proposed: Enderlein, 1913, with Cameron, 1888, and Kieffer, 1911, with (Tournier, 1877),
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http://dx.doi.org/10.3897/zookeys.1038.64978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154885PMC
May 2021

CO doping of organic interlayers for perovskite solar cells.

Nature 2021 06 2;594(7861):51-56. Epub 2021 Jun 2.

Department of Chemical and Biomolecular Engineering, New York University Tandon School of Engineering, New York, NY, USA.

In perovskite solar cells, doped organic semiconductors are often used as charge-extraction interlayers situated between the photoactive layer and the electrodes. The π-conjugated small molecule 2,2',7,7'-tetrakis[N,N-di(4-methoxyphenyl)amino]-9,9-spirobifluorene (spiro-OMeTAD) is the most frequently used semiconductor in the hole-conducting layer, and its electrical properties considerably affect the charge collection efficiencies of the solar cell. To enhance the electrical conductivity of spiro-OMeTAD, lithium bis(trifluoromethane)sulfonimide (LiTFSI) is typically used in a doping process, which is conventionally initiated by exposing spiro-OMeTAD:LiTFSI blend films to air and light for several hours. This process, in which oxygen acts as the p-type dopant, is time-intensive and largely depends on ambient conditions, and thus hinders the commercialization of perovskite solar cells. Here we report a fast and reproducible doping method that involves bubbling a spiro-OMeTAD:LiTFSI solution with CO under ultraviolet light. CO obtains electrons from photoexcited spiro-OMeTAD, rapidly promoting its p-type doping and resulting in the precipitation of carbonates. The CO-treated interlayer exhibits approximately 100 times higher conductivity than a pristine film while realizing stable, high-efficiency perovskite solar cells without any post-treatments. We also show that this method can be used to dope π-conjugated polymers.
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http://dx.doi.org/10.1038/s41586-021-03518-yDOI Listing
June 2021

Fish Oil, Se Yeast, and Micronutrient-Enriched Nutrition as Adjuvant Treatment during Target Therapy in a Murine Model of Lung Cancer.

Mar Drugs 2021 May 4;19(5). Epub 2021 May 4.

Department of Food Science, Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung 202, Taiwan.

Despite the effectiveness of primary treatment modalities for cancer, the side effects of treatments, medication resistance, and the deterioration of cachexia after disease progression lead to poor prognosis. A supportive treatment modality to overcome these limitations would be considered a major breakthrough. Here, we used two different target drugs to demonstrate whether a nutraceutical formula (fish oil, Se yeast, and micronutrient-enriched nutrition; NuF) can interfere with cancer cachexia and improve drug efficacy. After Lewis lung cancer (LLC) tumor injection, the C57BL/6 mice were orally administered targeted therapy drugs Iressa and Sutent alone or combined with NuF for 27 days. Sutent administration effectively inhibited tumor size but increased the number of lung metastases in the long term. Sutent combined with NuF had no significant difference in tumor weight and metastasis compare with Sutent alone. However, NuF slightly attenuated metastases number in lung may via mesenchymal marker N-cadherin suppression. NuF otherwise increased epithelial-like marker E-cadherin expression and induce NO-mediated intrinsic apoptotic pathway in tumor cells, thereby strengthening the ability of the targeted therapy drug Iressa for inhibiting tumor progression. Our results demonstrate that NuF can promote the anticancer effect of lung cancer to targeted therapy, especially in Iressa, by inhibiting HIF-1α and epithelial-mesenchymal transition (EMT) and inducing the apoptosis of lung cancer cells. Furthermore, NuF attenuates cancer-related cachectic symptoms by inhibiting systemic oxidative stress.
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http://dx.doi.org/10.3390/md19050262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147838PMC
May 2021

Exploring the relationship between the dielectric properties and viability of human normal hepatic tissues from 10 Hz to 100 MHz based on grey relational analysis and BP neural network.

Comput Biol Med 2021 07 15;134:104494. Epub 2021 May 15.

School of Biomedical Engineering, Air Force Medical University, Xi'an, China. Electronic address:

Liver is an important parenchyma organ, and its tissue viability plays an important role in liver transplantation and liver ischemic injury assessment. Dielectric property is a useful biophysical feature that provides insights into the structure and composition of biological tissues. This work aims to establish the relationship between the dielectric properties and viability of human normal hepatic tissues and explore the possibility of evaluating tissue viability by using dielectric properties. First, data on dielectric properties and tissue viability (including cell morphology and enzyme indicators) were collected from human liver tissues at 0.25-24 h after isolation. Grey relational analysis was conducted to select dielectric property and tissue viability indices that were highly correlated with prolonged ex vivo time as the inputs and outputs, respectively, of back-propagation (BP) neural network analysis. Finally, a BP neural network was developed with the Levenberg-Marquardt algorithm to explore the possibility of using dielectric properties as the basis for tissue viability evaluation. Results showed that the mean relative error for prediction was 2.40%, indicating that the model showed potential in forecasting liver tissue viability by applying dielectric properties.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104494DOI Listing
July 2021

Small-molecule inhibitor targeting the Hsp70-Bim protein-protein interaction in CML cells overcomes BCR-ABL-independent TKI resistance.

Leukemia 2021 May 18. Epub 2021 May 18.

State Key Laboratory of Fine Chemicals, Zhang Dayu School of Chemistry, Dalian University of Technology, Dalian, Liaoning, China.

Herein, we screened a novel inhibitor of the Hsp70-Bim protein-protein interaction (PPI), S1g-2, from a Bcl-2 inhibitor library; this compound specifically disrupted the Hsp70-Bim PPI by direct binding to an unknown site adjacent to that of an allosteric Hsp70 inhibitor MKT-077, showing binding affinity in sub-μM concentration range. S1g-2 exhibited overall 5-10-fold higher apoptosis-inducing activity in CML cells, primary CML blasts, and BCR-ABL-transformed BaF3 cells than other cancer cells, normal lymphocytes, and BaF3 cells, illustrating Hsp70-Bim PPI driven by BCR-ABL protects CML through oncoclient proteins that enriched in three pathways: eIF2 signaling, the regulation of eIF4E and p70S6K signaling, and the mTOR signaling pathways. Moreover, S1g-2 progressively enhanced lethality along with the increase in BCR-ABL-independent TKI resistance in the K562 cell lines and is more effective in primary samples from BCR-ABL-independent TKI-resistant patients than those from TKI-sensitive patients. By comparing the underlying mechanisms of S1g-2, MKT-077, and an ATP-competitive Hsp70 inhibitor VER-155008, the Hsp70-Bim PPI was identified to be a CML-specific target to protect from TKIs through the above three oncogenic signaling pathways. The in vivo activity against CML and low toxicity endows S1g-2 a first-in-class promising drug candidate for both TKI-sensitive and resistant CML.
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http://dx.doi.org/10.1038/s41375-021-01283-5DOI Listing
May 2021

Topographic Anatomy of the Zygomatico-Orbital Artery: Implications for Improving the Safety of Temporal Augmentation.

Plast Reconstr Surg 2021 Jul;148(1):19e-27e

From the State Key Laboratory of Oral Diseases, National State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, and Department of Cosmetic and Plastic Surgery, Oral and Maxillofacial Surgery, West China Hospital of Stomatology, the Department of Radiology, West China Hospital, and the Department of Human Anatomy, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University.

Background: Anatomical knowledge of the zygomatico-orbital artery and its most relevant clinical applications is essential for ensuring the safety of filler injection into the temporal region. The purpose of this study was to provide the precise position, detailed course, and relationship with surrounding structures of the zygomatico-orbital artery.

Methods: Fifty-eight patients who underwent head contrast-enhanced three-dimensional computed tomography and 10 fresh frozen cadavers were investigated.

Results: The zygomatico-orbital artery was identified in 93 percent of the samples in this work. Ninety-four percent of the zygomatico-orbital arteries derived directly from the superficial temporal artery, and the remaining arteries started from the frontal branch of the superficial temporal artery. According to the origin of the zygomatico-orbital artery, it was classified into type I and type II. Type I arteries were then classified into three subtypes. The trunk of the zygomatico-orbital artery was located between the deep temporal fascia and the superficial temporal fascia. Deep branches of the zygomatico-orbital artery pierced the superficial layer of the deep temporal fascia. The zygomatico-orbital artery originated from 11.3 mm in front of the midpoint of the apex of the tragus, and most of its trunks were located less than 20.0 mm above the zygomatic arch. The mean diameter of the zygomatico-orbital artery was 1.2 ± 0.2 mm. There were extensive anastomoses between the zygomatico-orbital artery and various periorbital arteries at the lateral orbital rim.

Conclusion: The precise anatomical knowledge of the zygomatico-orbital artery described in this study could be helpful for cosmetic physicians for improving the safety of temporal augmentation.
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http://dx.doi.org/10.1097/PRS.0000000000008100DOI Listing
July 2021

Deep convolution stack for waveform in underwater acoustic target recognition.

Sci Rep 2021 May 5;11(1):9614. Epub 2021 May 5.

Guangzhou Key Laboratory of Multilingual Intelligent Processing, Guangdong University of Foreign Studies, Guangzhou, 510006, China.

In underwater acoustic target recognition, deep learning methods have been proved to be effective on recognizing original signal waveform. Previous methods often utilize large convolutional kernels to extract features at the beginning of neural networks. It leads to a lack of depth and structural imbalance of networks. The power of nonlinear transformation brought by deep network has not been fully utilized. Deep convolution stack is a kind of network frame with flexible and balanced structure and it has not been explored well in underwater acoustic target recognition, even though such frame has been proven to be effective in other deep learning fields. In this paper, a multiscale residual unit (MSRU) is proposed to construct deep convolution stack network. Based on MSRU, a multiscale residual deep neural network (MSRDN) is presented to classify underwater acoustic target. Dataset acquired in a real-world scenario is used to verify the proposed unit and model. By adding MSRU into Generative Adversarial Networks, the validity of MSRU is proved. Finally, MSRDN achieves the best recognition accuracy of 83.15%, improved by 6.99% from the structure related networks which take the original signal waveform as input and 4.48% from the networks which take the time-frequency representation as input.
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http://dx.doi.org/10.1038/s41598-021-88799-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099869PMC
May 2021

Effects of extreme temperature on respiratory diseases in Lanzhou, a temperate climate city of China.

Environ Sci Pollut Res Int 2021 Sep 1;28(35):49278-49288. Epub 2021 May 1.

College of Atmospheric Sciences, Key Laboratory of Semi-Arid Climate Change, Ministry of Education, Lanzhou University, Lanzhou, 730000, China.

Under the global climate warming, extreme weather events occur more and more frequently. Epidemiological studies have proved that extreme temperature is strongly correlated with respiratory diseases. We evaluated extreme-temperature effect on respiratory emergency room (ER) visits for 5 years in Lanzhou, a northwest temperate climate city of China from January 1st, 2013, to August 31st, 2017. We built a distributed lag non-linear model (DLNM) to evaluate the lag effect up to 30 days. Results showed the relative risk (RR) of respiratory disease always reached the maximum at lag 0 day and decreased to 1.0 at lag 5 days. Extremely low temperature showed the lag effect of 22 days and the maximum RR was 1.415 (95% CI 1.295-1.546) at lag 0 day. Extremely high temperature showed the lag effect of 7 days and the maximum RR was 1.091 (95% CI 1.069-1.114) at lag 0 day. The elders (age > 65 years) were at the greatest risk to extreme temperatures and the response were very acute. Children (age ≤ 15 years) were at the lowest risk but the lag effect lasted the longest lag days than other subgroups. Males showed longer-term lag effect and higher RR than females. Our study indicated that the extremely low temperature has a significantly greater effect on respiratory diseases than extremely high temperature.
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http://dx.doi.org/10.1007/s11356-021-14169-xDOI Listing
September 2021

A novel Hsp70 inhibitor specifically targeting the cancer-related Hsp70-Bim protein-protein interaction.

Eur J Med Chem 2021 Aug 14;220:113452. Epub 2021 Apr 14.

State Key Laboratory of Fine Chemicals, Zhang Dayu School of Chemistry, Dalian University of Technology, Dalian, Liaoning, 116024, China. Electronic address:

Targeting cancer-related Hsp70-Bim protein-protein interactions (PPIs) offers a new strategy for the design of Hsp70 inhibitors. Herein, we discovered a novel Hsp70 inhibitor, S1g-6, based on the established BH3 mimetics. S1g-6 exhibited sub-μM binding affinity toward Hsp70 and selectively disrupted Hsp70-Bim PPI. The target specificity of S1g-6in situ was validated by affinity-based protein profiling, co-immunoprecipitation, and cell-based shRNA assays. S1g-6 specifically antagonized the ATPase activity of Hsp70 upon recruiting Bim and showed selective apoptosis induction in some cancer cell lines over normal ones through suppression of some oncogenic clients of Hsp70, representing a new class of antitumor candidates. Hsp70-Bim PPI exhibited cancer-dependent role as a potential anti-cancer target.
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http://dx.doi.org/10.1016/j.ejmech.2021.113452DOI Listing
August 2021

Association between environmental factors and COVID-19 in Shanghai, China.

Environ Sci Pollut Res Int 2021 Sep 15;28(33):45087-45095. Epub 2021 Apr 15.

College of Atmospheric Sciences, Key Laboratory of Semi-Arid Climate Change, Ministry of Education, Lanzhou University, Lanzhou, 730000, China.

The outbreak of coronavirus disease 2019 (COVID-19) continues to spread worldwide and has led to recession, rising unemployment, and the collapse of the health-care system. The aim of this study was to explore the exposure-response relationship between daily confirmed COVID-19 cases and environmental factors. We used a time-series generalized additive model (GAM) to investigate the short-term association between COVID-19 and environmental factors by using daily meteorological elements, air pollutant concentration, and daily confirmed COVID-19 cases from January 21, 2020, to February 29, 2020, in Shanghai, China. We observed significant negative associations between daily confirmed COVID-19 cases and mean temperature (T), temperature humidity index (THI), and index of wind effect (K), whereas air quality index (AQI), PM, PM NO, and SO were significantly associated with the increase in daily confirmed COVID-19 cases. A 1 °C increase in T, one-unit increase in THI, and 10-unit increase in K (lag 0-7 days) were associated with 4.7, 1.8, and 1.6% decrease in daily confirmed cases, respectively. Daily T, THI, K, PM, and SO had significant lag and persistence (lag 0-7 days), whereas the lag and persistence of AQI, PM, and NO were significant at both lag 0-7 and 0-14 days. A 10-μg/m increase in PM and 1-μg/m increase in SO was associated with 13.9 and 5.7% increase in daily confirmed cases at lag 0-7 days, respectively, whereas a 10-unit increase in AQI and a 10-μg/m increase in PM and NO were associated with 7.9, 7.8, and 10.1% increase in daily confirmed cases at lag 0-14 days, respectively. Our findings have important implications for public health in the city of Shanghai.
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http://dx.doi.org/10.1007/s11356-021-13834-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047551PMC
September 2021

Visual Impairment and Objectively Measured Physical Activity in Middle-Aged and Older Adults.

J Gerontol A Biol Sci Med Sci 2021 Apr 10. Epub 2021 Apr 10.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Background: Vision loss is associated with increased falls risk and restricted physical activity, yet the relationship between multiple vision measures and objectively measured physical activity, especially activity patterns, in mid-to-late life is not well understood.

Methods: This study included 603 participants aged ≥ 50 years (mean age=73.5) in the Baltimore Longitudinal Study of Aging who had the following assessments: presenting and best-corrected visual acuity, contrast sensitivity, visual fields, stereo acuity, and free-living physical activity using a wrist-worn ActiGraph accelerometer for 7 days. Linear regression models were used to examine the association between vision measures and daily activity counts, active minutes, and activity fragmentation (defined as an active-to-sedentary transition probability), adjusting for potential confounders. Mixed-effects models estimated differences in activity by time of day comparing those with and without each visual impairment.

Results: In the fully adjusted model, worse presenting visual acuity, contrast sensitivity, and visual fields were associated with fewer activity counts, less active time, and more fragmented activity patterns (p<0.05 for all). Participants with presenting or best-corrected visual acuity impairment had 19.2 and 29.3 fewer active minutes (p=0.05, p=0.03, respectively) per day. Visual field impairment was associated with 268,636 fewer activity counts (p=0.02), 46.2 fewer active minutes (p=0.02) per day, and 3% greater activity fragmentation (p=0.009). Differences in activity levels tended to be greatest from 6am-6pm (p<0.05).

Conclusions: Older adults with visual impairment have restricted and more fragmented patterns of daily activity. Longitudinal studies to quantify the long-term impacts of visual impairments on activity decline are warranted.
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http://dx.doi.org/10.1093/gerona/glab103DOI Listing
April 2021

The α2δ-1-NMDAR1 interaction in the trigeminal ganglion contributes to orofacial ectopic pain following inferior alveolar nerve injury.

Brain Res Bull 2021 Jun 31;171:162-171. Epub 2021 Mar 31.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address:

Orofacial ectopic pain can often arise following nerve injury. However, the exact mechanism responsible for orofacial ectopic pain induced by trigeminal nerve injury remains unknown. The α2δ-1 and glutamate N-methyl-d-aspartic acid receptor (NMDAR) interactions have been demonstrated to participate in neuropathic pain regulation in the spinal cord. In this study, a rat model of inferior alveolar nerve transection (IANX) was used to investigate the role of α2δ-1-NMDAR1 interaction in the trigeminal ganglion (TG) in regard to the regulation of orofacial ectopic pain. Western blot (WB) analysis indicated that α2δ-1 and NMDAR1 in the TG were substantially higher in IANX rats than they were in sham/naive rats. Additionally, immunofluorescence (IF) results revealed that α2δ-1 and NMDAR1 were co-expressed and distributed within neurons and activated satellite glial cells in the TG. Co-immunoprecipitation (Co-IP) results indicated that α2δ-1-NMDAR1 complex levels in the TG were higher in IANX rats than they were in sham rats. Furthermore, the results of behavioral tests demonstrated that intra-TG injection of gabapentin (α2δ-1 inhibitory ligand) or memantine hydrochloride (NMDAR antagonist) reversed the decrease in mechanical head-withdrawal threshold (HWT) in IANX rats. Moreover, inhibition of α2δ-1 by intra-TG administration of gabapentin suppressed the upregulation of the NMDAR1 protein, and the inhibition of NMDAR by intra-TG administration of memantine hydrochloride inhibited the increased expression of α2δ-1 protein induced by IANX. In conclusion, the physical and functional interaction between α2δ-1 and NMDAR1 is critical for the development of orofacial ectopic pain, indicating that α2δ-1, NMDAR1, and the α2δ-1-NMDAR1 complex may represent potential targets for the treatment of orofacial ectopic pain.
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http://dx.doi.org/10.1016/j.brainresbull.2021.03.019DOI Listing
June 2021
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