Publications by authors named "Hang Li"

890 Publications

Universal Structural Influence on the 2D Electron Gas at SrTiO Surfaces.

Adv Sci (Weinh) 2021 Sep 17:e2100602. Epub 2021 Sep 17.

Photon Science Division, Paul Scherrer Institut, Villigen, CH-5232, Switzerland.

The 2-dimensional electron gas (2DEG) found at the surface of SrTiO and related interfaces has attracted significant attention as a promising basis for oxide electronics. In order to utilize its full potential, the response of this 2DEG to structural changes and surface modification must be understood in detail. Here, a study of the detailed electronic structure evolution of the 2DEG as a function of sample temperature and surface step density is presented. By comparing the experimental results with ab initio calculations, it is shown that local structure relaxations cause a metal-insulator transition of the system around 135 K. This study presents a new and simple way of tuning the 2DEG via surface vicinality and identifies how the operation of prospective devices will respond to changes in temperature.
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http://dx.doi.org/10.1002/advs.202100602DOI Listing
September 2021

Impact of Endometrial Thickness and Volume Compaction on the Live Birth Rate Following Fresh Embryo Transfer of In Vitro Fertilization.

J Ultrasound Med 2021 Sep 16. Epub 2021 Sep 16.

Department of Obstetrics and Gynaecology, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China.

Objectives: The aim of our study was to compare the live birth rate following fresh embryo transfer (ET) during in vitro fertilization (IVF) in women with or without endometrial compaction in thickness and volume between the day of human chorionic gonadotrophin (hCG) and the ET day.

Methods: This is a retrospective analysis of infertile women undergoing the first IVF cycle with fresh ET. A single operator performed all the ultrasound measurements for endometrial thickness and endometrial volume using three-dimensional ultrasound. Endometrial compaction was calculated as the difference of the measurement between the hCG day and ET day. The predictive values of age of women, number of embryos transferred, and endometrial compaction in thickness and volume on live birth were studied.

Results: A total of 268 women who underwent the first IVF cycle with fresh ET between June 2005 and August 2006 were included in this retrospective analysis. Endometrial thickness was significantly higher on the ET day than the hCG day while endometrial volume was significantly smaller on the ET day than the hCG day. Women with a live birth were younger, had a higher serum estradiol level on the hCG day, and similar absolute or percentage change of endometrial thickness and volume when compared to those without a live birth.

Conclusion: Endometrial thickness and volume compaction was not a significant predictor of live birth in the multivariate logistic regression model. Endometrial thickness and volume compaction did not affect the live birth rate in the fresh IVF cycle.
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http://dx.doi.org/10.1002/jum.15830DOI Listing
September 2021

DNA Three-Way Junction with Multiple Recognition Regions Mediated an Unconfined DNA Walker for Electrochemical Ultrasensitive Detection of miRNA-182-5p.

Anal Chem 2021 Sep 13. Epub 2021 Sep 13.

Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, PR China.

In this work, a DNA three-way junction (TWJ) with multiple recognition regions was intelligently engineered, which could be applied as an unconfined DNA walker with a rapid walking speed and high sensitivity for electrochemical detection of microRNA (miRNA-182-5p). Once the target miRNA was presented, the hairpins on TWJ could be successively opened to form an annular DNA walker, which could walk on the entire scope of the electrode surface without the confine for the length of DNA walker legs compared with the traditional DNA walker, greatly improving the walking efficiency. In addition, this DNA walker with multirecognition segments could obviously increase the local concentration of recognition sites, which significantly enhanced the detection speed and sensitivity. As a result, this proposed biosensor with annular DNA as a walker could dexterously achieve the ultrasensitive and fast detection of miRNA-182-5p from 0.1 fM to 1 nM with a detection limit of 31.13 aM. Meaningfully, this strategy explored an innovative path in the design of a new DNA walker nanostructure for accomplishing speedy and sensitive detection of biomarkers.
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http://dx.doi.org/10.1021/acs.analchem.1c02668DOI Listing
September 2021

Analysis of Glomerular IgG Subclasses Switch in Idiopathic Membranous Nephropathy Classified by Glomerular Phospholipase A2 Receptor Antigen and Serum Antibody.

Dis Markers 2021 30;2021:9965343. Epub 2021 Aug 30.

Nephrology Division, Peking Union Medical College Hospital, Beijing 100730, China.

Background: The role of IgG subclass in idiopathic membranous nephropathy (IMN) was unclarified. Recent study found IgG subtype switches from IgG1 to IgG4 in the early pathological stage in IMN. The profile of IgG subclass in phospholipase A2 receptor- (PLA2R-) related and PLA2R-unrelated IMN was unrevealed. Our study is aimed at testifying whether IgG subclass switch existed in PLA2R-related and PLA2R-unrelated IMN, respectively.

Methods: Our study retrospectively enrolled 157 Chinese patients with biopsy-confirmed IMN between September 2017 and November 2019. We measured glomerular PLA2R antigen and serum anti-PLA2R antibody to classify the patients into PLA2R-related ( = 132) and PLA2R-unrelated ( = 25) subgroup. We evaluated glomerular IgG subclass by immunofluorescence (IF) predominance. Our study defined IgG subclass deposition as predominant if the IF score was higher than the other three and ≥1 +, or as codominant if the IF intensity was equal to any other and ≥1 +. We explored the relationship between IF predominance of glomerular IgG subtype and electron microscopic (EM) stages of IMN.

Results: We did not find statistical difference of predominant or codominant rate (pre/co-rate) among EM stages in any subclass ( > 0.05). Pre/co-rate of IgG3 linearly associated with EM stage in total and PLA2R-related subgroup ( = 0.044, = 0.013). PLA2R-related subgroup showed higher IgG4 intensity (2.1 ± 0.6 vs. 1.6 ± 0.7, = 0.001) and pre/co-rate of IgG4 in stage 1 (97% vs. 57%, = 0.015) than PLA2R-unrelated group. We found no difference of IgG subclass pre/co-rate in different EM stages or linear association between pre/co-rate of IgG1, IgG2, IgG4, and EM stages ( > 0.05).

Conclusions: Pre/co-rate of IgG3 declined with EM stage in total and PLA2R-related subgroup. We did not find IgG subclass switches from IgG1 to IgG4 in either IMN patients or subgroups.
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http://dx.doi.org/10.1155/2021/9965343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421165PMC
August 2021

The Effector SdjA Is a Bifunctional Enzyme That Distinctly Regulates Phosphoribosyl Ubiquitination.

mBio 2021 Sep 7:e0231621. Epub 2021 Sep 7.

Department of Biological Sciences, Purdue University, West Lafayette, Indiana, USA.

Legionella pneumophila promotes its survival and replication in phagocytes by actively modulating cellular processes using effectors injected into host cells by its Dot/Icm type IV secretion system. Many of these effectors function to manipulate the ubiquitin network of infected cells, thus contributing to the biogenesis of the -containing vacuole (LCV), which is permissive for bacterial replication. Among these, members of the SidE effector family (SidEs) catalyze ubiquitination of functionally diverse host proteins by a mechanism that is chemically distinct from the canonical three-enzyme cascade. The activity of SidEs is regulated by two mechanisms: reversal of the phosphoribosyl ubiquitination by DupA and DupB and direct inactivation by SidJ, which is a calmodulin-dependent glutamylase. In many L. pneumophila strains, SidJ belongs to a two-member protein family. Its homolog SdjA appears to function differently from SidJ despite the high-level similarity in their primary sequences. Here, we found that SdjA is a bifunctional enzyme that exhibits distinct activities toward members of the SidE family. It inhibits the activity of SdeB and SdeC by glutamylation. Unexpectedly, it also functions as a deglutamylase that reverses SidJ-induced glutamylation on SdeA. Our results reveal that an enzyme can catalyze two completely opposite biochemical reactions, which highlights the distinct regulation of phosphoribosyl ubiquitination by the SidJ effector family. One unique feature of L. pneumophila Dot/Icm effectors is the existence of protein families with members of high-level similarity. Whereas members of some families are functionally redundant, as suggested by their primary sequences, the relationship between SidJ and SdjA, the two members of the SidJ family, has remained mysterious. Despite their sharing 57% identity, cannot complement the defects in virulence displayed by a mutant lacking . SidJ inhibits the activity of the SidE family by a calmodulin (CaM)-dependent glutamylase activity. Here, we found that SdjA is a dual function protein: it is a CaM-dependent glutamylase against SdeB and SdeC but exhibits deglutamylase activity toward SdeA that has been modified by SidJ, indicating that SdjA functions to fine-tune the activity of SidEs. These findings have paved the way for future structural and functional analysis of SdjA, which may reveal novel mechanism for isopeptide bond cleavage and provide insights into the study of protein evolution.
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http://dx.doi.org/10.1128/mBio.02316-21DOI Listing
September 2021

A machine learning-based biological aging prediction and its associations with healthy lifestyles: the Dongfeng-Tongji cohort.

Ann N Y Acad Sci 2021 Sep 3. Epub 2021 Sep 3.

Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

This study aims to establish a biological age (BA) predictor and to investigate the roles of lifestyles on biological aging. The 14,848 participants with the available information of multisystem measurements from the Dongfeng-Tongji cohort were used to estimate BA. We developed a composite BA predictor showing a high correlation with chronological age (CA) (r = 0.82) by using an extreme gradient boosting (XGBoost) algorithm. The average frequency hearing threshold, forced expiratory volume in 1 second (FEV ), gender, systolic blood pressure, and homocysteine ranked as the top five important features for the BA predictor. Two aging indexes, recorded as the AgingAccel (the residual from regressing predicted age on CA) and aging rate (the ratio of predicted age to CA), showed positive associations with the risks of all-cause (HR (95% CI) = 1.12 (1.10-1.14) and 1.08 (1.07-1.10), respectively) and cause-specific (HRs ranged from 1.06 to ∼1.15) mortality. Each 1-point increase in healthy lifestyle score (including normal body mass index, never smoking, moderate alcohol drinking, physically active, and sleep 7-9 h/night) was associated with a 0.21-year decrease in the AgingAccel (95% CI: -0.27 to -0.15) and a 0.4% decrease in the aging rate (95% CI: -0.5% to -0.3%). This study developed a machine learning-based BA predictor in a prospective Chinese cohort. Adherence to healthy lifestyles showed associations with delayed biological aging, which highlights potential preventive interventions.
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http://dx.doi.org/10.1111/nyas.14685DOI Listing
September 2021

Nonvolatile magnetoelectric coupling in two-dimensional ferromagnetic-bilayer/ferroelectric van der Waals heterostructures.

Nanoscale 2021 Sep 13;13(33):14214-14220. Epub 2021 Aug 13.

International Joint Research Laboratory of New Energy Materials and Devices of Henan Province, School of Physics and Electronics, Henan University, Kaifeng 475004, PR China.

One of the promising research topics on two-dimensional (2D) van der Waals (vdW) material based devices is the nonvolatile electrical control of magnetism. Usually, it is very hard to tune ferromagnetic or antiferromagnetic ordering by ferroelectric polarization due to strong exchange coupling. The existence of vdW layer spacing, however, which is ubiquitous in 2D materials, makes interlayer magnetic exchange coupling much weaker than interlayer coupling. In this work, we design a multiferroic heterostructure composed of a CrOBr ferromagnetic bilayer and an InSe ferroelectric monolayer. The weaker interlayer exchange coupling of the CrOBr bilayer makes it easier to be regulated by ferroelectric polarization, enabling reversible nonvolatile electric control of shifts between ferromagnetic and antiferromagnetic ordering. The unique electrically controlled interlayer magnetic coupling for tuning the overall magnetism may be available for the practical application of 2D vdW bilayer magnets in high-sensitivity sensors and high-density data storage.
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http://dx.doi.org/10.1039/d1nr01093jDOI Listing
September 2021

The Change in the Neutrophil/Lymphocyte Ratio Predicts the Prognosis of Patients with Cryptococcal Meningitis.

Mycopathologia 2021 Aug 31. Epub 2021 Aug 31.

Department of Neurology, Jiangxi Chest Hospital, Nanchang, 330000, Jiangxi, People's Republic of China.

Purpose: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been studied in many diseases. However, their roles in cryptococcal meningitis (CM) are unclear. The purpose of this article was to analyse the roles of the PLR and NLR in CM patients during treatment.

Methods: 139 newly diagnosed CM patients were enrolled. We divided patients into two groups: the successful group (n = 121) and the failure group (n = 18) based on the prognosis of patients. Then, we analyzed changes in clinical data of two groups, which were measured at the time of admission, after 2 weeks and 4 weeks in the hospital. Then the patients were divided into HIV group (n = 26) and non-HIV group (n = 113) to determine whether HIV status had an impact on the prognosis and clinical data of patients.

Results: Most patients were male living in rural areas; headache was the most common symptom before admission. In the subgroup analysis based on HIV status, there were significantly fewer patients with HIV (26 individuals) than without HIV (113 individuals), and 40.7% non-HIV CM patients had no underlying diseases. There was no significant difference in prognosis (p = 0.746), lymphocytes (p = 0.109) or neutrophils (p = 0.269) between patients with and without HIV. A mixed-effect model indicated that there was no difference (p = 0.171) in PLR between successful group and failure group. However, the change of NLR was statistically significant (p = 0.004 < 0.05) between successful group and failure group.

Conclusion: An increase in the NLR during treatment may be used as an indicator of treatment failure.
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http://dx.doi.org/10.1007/s11046-021-00553-1DOI Listing
August 2021

Antibacterial Dual Network Hydrogels for Sensing and Human Health Monitoring.

Adv Healthc Mater 2021 Aug 28:e2101089. Epub 2021 Aug 28.

Shaanxi Key Laboratory of Degradable Biomedical Materials, Shaanxi R&D Center of Biomaterials and Fermentation Engineering, Biotech. & Biomed. Research Institute, Northwest University, Taibai North Road 229, Xi'an, Shaanxi, 710069, China.

Polymer-based conductive hydrogels have the synergistic advantages of high conductivity and tissue-like properties, making them promising candidates for the construction of flexible electronic devices. However, conductive hydrogel materials can easily absorb microorganisms due to their high water content. To address the problem that conductive hydrogels are susceptible to infection by external pathogens when monitoring wounds and when used in implanted organs, tannic acid-borax (TA-B) complexes are introduced into classical dual network polyacrylamide/agarose (PAM/Agar) hydrogels to form PAM/Agar/TA-B hydrogel conductors. These hydrogels are antibacterial and have good mechanical properties, light transmission, electrical conductivity, and adhesion. TA-B increases the compressive stress of the PAM/Agar/TA-B hydrogel by 58.14% compared to a PAM/Agar hydrogel. The PAM/Agar/TA-B hydrogel can be used as an electronic conductor for electronic skin and wearable sensors. Outstanding biocompatibility allows the hydrogel to be used as a monitoring device at wounds to monitor heartbeat, skin wounds, and internal tissue status in real time. In summary, an antibacterial strain sensing matrix that is safe for human health monitoring is developed.
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http://dx.doi.org/10.1002/adhm.202101089DOI Listing
August 2021

Internet-Based HIV Self-Testing Among Men Who Have Sex With Men Through Pre-exposure Prophylaxis: 3-Month Prospective Cohort Analysis From China.

J Med Internet Res 2021 Aug 27;23(8):e23978. Epub 2021 Aug 27.

NHC Key Laboratory of AIDS Immunology, National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China.

Background: Routine HIV testing accompanied with pre-exposure prophylaxis (PrEP) requires innovative support in a real-world setting.

Objective: This study aimed to determine the usage of HIV self-testing (HIVST) kits and their secondary distribution to partners among men who have sex with men (MSM) in China, who use PrEP, in an observational study between 2018 and 2019.

Methods: In 4 major cities in China, we prospectively followed-up MSM from the China Real-world oral PrEP demonstration study, which provides daily or on-demand PrEP for 12 months, to assess the usage and secondary distribution of HIVST on quarterly follow-ups. Half of the PrEP users were randomized to receive 2 HIVSTs per month in addition to quarterly facility-based HIV testing. We evaluated the feasibility of providing HIVST to PrEP users.

Results: We recruited 939 MSM and randomized 471 to receive HIVST, among whom 235 (49.9%) were daily and 236 (50.1%) were on-demand PrEP users. At baseline, the median age was 29 years, 390 (82.0%) men had at least college-level education, and 119 (25.3%) had never undergone facility-based HIV testing before. Three months after PrEP initiation, 341 (74.5%) men had used the HIVST provided to them and found it very easy to use. Among them, 180 of 341 (52.8%) men had distributed the HIVST kits it to other MSM, and 132 (51.6%) among the 256 men who returned HIVST results reported that used it with their sexual partners at the onset of intercourse. Participants on daily PrEP were more likely to use HIVST (adjusted hazard ratio=1.3, 95% CI 1.0-1.6) and distribute HIVST kits (adjusted hazard ratio=1.3, 95% CI 1.1-1.7) than those using on-demand PrEP.

Conclusions: MSM who used PrEP had a high rate of usage and secondary distribution of HIVST kits, especially among those on daily PrEP, which suggested high feasibility and necessity for HIVST after PrEP initiation. Assuming that fourth-generation HIVST kits are available, HIVST may be able to replace facility-based HIV testing to a certain extent.

Trial Registration: Chinese Clinical Trial Registry ChiCTR1800020374; https://www.chictr.org.cn/showprojen.aspx?proj=32481.

International Registered Report Identifier (irrid): RR2-10.1136/bmjopen-2019-036231.
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http://dx.doi.org/10.2196/23978DOI Listing
August 2021

Phenolic Content, Main Flavonoids, and Antioxidant Capacity of Instant Sweet Tea ( [Hance] Chun) Prepared with Different Raw Materials and Drying Methods.

Foods 2021 Aug 19;10(8). Epub 2021 Aug 19.

Research Center for Plants and Human Health, Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu 610213, China.

This study aims to investigate the effects of raw materials and drying methods on the phytochemical and antioxidant capacities of instant sweet tea powder. Four raw materials of sweet tea leave powders (STUT) were extracted and dried with two methods (freeze-drying and spray-drying). The antioxidant capacity, total phenolic content (TPC), total flavonoid content (TFC), and phlorizin and trilobatin contents of obtained instant sweet tea powders were compared. In addition, the single-factor experiments coupled with response surface methodology were used to study the influences of solvent-to-sample ratio, extraction temperature, extraction time, and their interactions on instant sweet tea yield. Results showed that the optimal conditions for extraction were the solvent-to-sample ratio of 19:1 mL/g, extraction temperature of 88 °C, and extraction time of 30 min. The TPC, TFC, antioxidant capacities, and phloridzin and trilobatin contents of instant sweet teas were higher than those of STUT, and the TPC and TFC of freeze-dried instant sweet teas were higher than those of spray-dried instant sweet teas. Significant correlations were found among TPC, TFC, and antioxidant capacities ( < 0.01). The freeze-dried instant sweet tea produced by young leaves (prepared by oven-drying) showed the highest TPC, TFC, and antioxidant capacities, compared with other raw materials and drying methods.
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http://dx.doi.org/10.3390/foods10081930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394704PMC
August 2021

The Chemical, Structural, and Biological Properties of Crude Polysaccharides from Sweet Tea ( (Hance) Chun) Based on Different Extraction Technologies.

Foods 2021 Jul 31;10(8). Epub 2021 Jul 31.

National Agricultural Science & Technology Center, Chengdu 610213, China.

Eight extraction technologies were used to extract sweet tea ( (Hance) Chun) crude polysaccharides (STPs), and their chemical, structural, and biological properties were studied and compared. Results revealed that the compositions, structures, and biological properties of STPs varied dependent on different extraction technologies. Protein-bound polysaccharides and some hemicellulose could be extracted from sweet tea with diluted alkali solution. STPs extracted by deep-eutectic solvents and diluted alkali solution exhibited the most favorable biological properties. Moreover, according to the heat map, total phenolic content was most strongly correlated with biological properties, indicating that the presence of phenolic compounds in STPs might be the main contributor to their biological properties. To the best of our knowledge, this study reports the chemical, structural, and biological properties of STPs, and the results contribute to understanding the relationship between the chemical composition and biological properties of STPs.
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http://dx.doi.org/10.3390/foods10081779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391304PMC
July 2021

SLC-30A9 is required for Zn homeostasis, Zn mobilization, and mitochondrial health.

Proc Natl Acad Sci U S A 2021 Aug;118(35)

National Laboratory of Biomacromolecules, Chinese Academy of Sciences Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;

The trace element zinc is essential for many aspects of physiology. The mitochondrion is a major Zn store, and excessive mitochondrial Zn is linked to neurodegeneration. How mitochondria maintain their Zn homeostasis is unknown. Here, we find that the SLC-30A9 transporter localizes on mitochondria and is required for export of Zn from mitochondria in both and human cells. Loss of leads to elevated Zn levels in mitochondria, a severely swollen mitochondrial matrix in many tissues, compromised mitochondrial metabolic function, reductive stress, and induction of the mitochondrial stress response. SLC-30A9 is also essential for organismal fertility and sperm activation in , during which Zn exits from mitochondria and acts as an activation signal. In -deficient neurons, misshapen mitochondria show reduced distribution in axons and dendrites, providing a potential mechanism for the Birk-Landau-Perez cerebrorenal syndrome where an mutation was found.
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http://dx.doi.org/10.1073/pnas.2023909118DOI Listing
August 2021

Programming a ""-like DNA Nanomachine as a Super Signal Amplifier for Ultrasensitive Electrochemical Assay of Hg.

Anal Chem 2021 09 24;93(35):12075-12080. Epub 2021 Aug 24.

Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, PR China.

Herein, with skillfully engaging stable T-Hg-T bonding, a ""-like DNA nanomachine with concise and highly efficient assembly and enhanced recognition/conversion efficiency was engineered as a super signal amplifier, which was united with [email protected]@Pt multimetallic mesoporous nanomaterials ([email protected]@Pt MMNs) for ultrasensitive electrochemical assay of mercury ions (Hg). Specifically, the formed ""-like DNA nanomachine could simultaneously trigger four same cascade DNAzyme cleavage reactions with the help of Mg DNAzyme for markedly converting target Hg to enormous DNA segments labeled with ferrocene (Fc), improving the detection sensitivity. Subsequently, the prepared [email protected]@Pt MMNs could not only show commendable electrochemical catalysis to Fc but also act as an excellent immobilization matrix for capturing and accumulating abundant Fc around them to further strengthen the electrochemical signal. As a result, the well-designed electrochemical sensor could achieve a low limit of detection of 3.58 fM in the range from 10 fM to 100 nM for Hgdetection. This strategy offers a simple and rapid avenue to detect heavy metal ions and shows promising application potential for environmental pollutant monitoring.
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http://dx.doi.org/10.1021/acs.analchem.1c02343DOI Listing
September 2021

GLIS family zinc finger 3 promoting cell malignant behaviors and NF-κB signaling in glioma.

Brain Res 2021 Nov 14;1770:147623. Epub 2021 Aug 14.

Department of Hyperbaric Oxygen, Sixth Medical Center, Chinese PLA General Hospital, No. 6 FuCheng Road, Haidian District, Beijing, China. Electronic address:

Glioma is a common tumor in the human central nervous system. However, its molecular mechanism in the pathogenesis and regulation of glioma progression is still unclear. In this study, we found that GLIS3 was up-regulated in glioma tissues, and the increased expression is positively correlated with advanced tumor grade. Survival evaluation disclosed that patients with high expression levels of GLIS3 normally have a poor prognosis. Functional analysis revealed the oncogenic role of GLIS3 in the development of glioma. GLIS3 promotes glioma cells' invasion, migration, and proliferation. Meanwhile, deficiency of GLIS3 produces an inhibitory function upon NF-κB signaling pathway. This work demonstrated that GLIS3, acting as a target and prognostic factor for glioma, may promote the invasion, migration and proliferation of glioma cells involved in regulation of NF-κB signaling pathway.
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http://dx.doi.org/10.1016/j.brainres.2021.147623DOI Listing
November 2021

Association of HOTAIR Polymorphisms with Susceptibility to Psoriasis in a Chinese Han Population.

Biomed Res Int 2021 4;2021:5522075. Epub 2021 Aug 4.

Department of Dermatology, Peking University First Hospital, Beijing, China.

Psoriasis is a common disease in dermatology, but its etiology and pathogenesis have not been fully elucidated. In recent years, researchers have found that HOX transcript antisense RNA (HOTAIR) plays an important role in biological processes as an important long-chain noncoding RNA (lncRNA). The goal of this study was to investigate the association between HOTAIR polymorphisms and psoriasis in a Chinese Han population by screening key candidate single-nucleotide polymorphism (SNPs) sites in HOTAIR. A total of 269 patients diagnosed with psoriasis and 273 healthy control subjects were enrolled in this case-control study. Three SNPs of HOTAIR were genotyped: SNP1 (rs12826786), SNP2 (rs1899663), and SNP3 (rs4759314). All polymorphisms were in Hardy-Weinberg equilibrium in both the control and patient groups, and the SNPs were in linkage disequilibrium. The distribution of the rs4759314 genotype in the control group and case group was statistically significant according to all the models except the recessive model (adjusted value < 0.05), and the CCG haplotype group had a significant difference (OR (95%CI) = 2.907 (1.344 - 6.289), adjusted value = 0.0263). rs12826786 was associated with a risk of psoriasis according to the dominant model (C/T-T/T vs. C/C: OR (95%CI) = 0.70 (0.48 - 1.01), adjusted value = 0.049) and overdominant model (C/T vs. C/C-T/T: OR (95%CI) = 0.69 (0.47 - 1.01), adjusted value = 0.048). The current work showed that a genomic variant within HOTAIR was associated with a risk of psoriasis, and the clinical value of this study should be further evaluated in the future.
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http://dx.doi.org/10.1155/2021/5522075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357505PMC
August 2021

Atrophic pigmented dermatofibrosarcoma protuberans misdiagnosed as hyperpigmentation.

Indian J Dermatol Venereol Leprol 2021 Sep-Oct;87(5):693-695

Department of Dermatology and Venereology, Peking University First Hospital, Xicheng, Beijing, China.

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http://dx.doi.org/10.25259/IJDVL_713_20DOI Listing
May 2020

Recent Advances in Bioactive Compounds, Health Functions, and Safety Concerns of Onion ( L.).

Front Nutr 2021 22;8:669805. Epub 2021 Jul 22.

Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu, China.

Onion ( L.) is a common vegetable, widely consumed all over the world. Onion contains diverse phytochemicals, including organosulfur compounds, phenolic compounds, polysaccharides, and saponins. The phenolic and sulfur-containing compounds, including onionin A, cysteine sulfoxides, quercetin, and quercetin glucosides, are the major bioactive constituents of onion. Accumulated studies have revealed that onion and its bioactive compounds possess various health functions, such as antioxidant, antimicrobial, anti-inflammatory, anti-obesity, anti-diabetic, anticancer, cardiovascular protective, neuroprotective, hepatorenal protective, respiratory protective, digestive system protective, reproductive protective, and immunomodulatory properties. Herein, the main bioactive compounds in onion are summarized, followed by intensively discussing its major health functions as well as relevant molecular mechanisms. Moreover, the potential safety concerns about onion contamination and the ways to mitigate these issues are also discussed. We hope that this paper can attract broader attention to onion and its bioactive compounds, which are promising ingredients in the development of functional foods and nutraceuticals for preventing and managing certain chronic diseases.
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http://dx.doi.org/10.3389/fnut.2021.669805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339303PMC
July 2021

Novel parameter based on lipid indicators ratio improves prognostic value of plasma lipid levels in resectable colorectal cancer patients.

World J Gastrointest Surg 2021 Jul;13(7):689-701

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.

Background: At present, the value of lipid indicators in evaluating the prognosis of colorectal cancer is still relatively limited.

Aim: To evaluate the value of a novel parameter for colorectal cancer (CRC) prognosis scoring based on preoperative serum lipid levels.

Methods: Four key serum lipid factors, namely, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB), were detected. Two representative ratios, HDL-C-LDL-C ratio (HLR) and ApoA1-ApoB ratio (ABR) were calculated. The relationship of these parameters with the prognosis of CRC patients including progression-free survival (PFS) and overall survival (OS) was analyzed by Kaplan-Meier plot and Cox proportional hazards regression. A novel lipoprotein cholesterol-apolipoprotein (LA) score based on HLR and ABR was established and its value in prognosis evaluation for CRC patients was explored.

Results: Multivariate Cox proportional hazards regression analysis of PFS and OS showed that HDL-C, ApoA1, HLR, and ABR were positively associated with the prognosis of CRC patients. LA score was independently associated with a good prognosis in resectable CRC patients. Data processing of a dummy variable showed that the prognosis of patients with higher LA scores is better than that with lower LA scores.

Conclusion: The newly established LA score might serve as a better predictor of the prognosis of resectable CRC patients.
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http://dx.doi.org/10.4240/wjgs.v13.i7.689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316850PMC
July 2021

Network pharmacology to investigate the pharmacological mechanisms of muscone in Xingnaojing injections for the treatment of severe traumatic brain injury.

PeerJ 2021 20;9:e11696. Epub 2021 Jul 20.

The Fifth Clinical Medical College of Anhui Medical University, Beijing, China.

Background: Xingnaojing injections (XNJI) are widely used in Chinese medicine to mitigate brain injuries. An increasing number of studies have shown that XNJI may improve neurological function. However, XNJI's active ingredients and molecular mechanisms when treating traumatic brain injury (TBI) are unknown.

Methods: XNJI's chemical composition was acquisited from literature and the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. We used the "absorption, distribution, metabolism, and excretion" (ADME) parameter-based virtual algorithm to further identify the bioactive components. We then screened data and obtained target information regarding TBI and treatment compounds from public databases. Using a Venn diagram, we intersected the information to determine the hub targets. Cytoscape was used to construct and visualize the network. In accordance with the hub proteins, we then created a protein-protein interaction (PPI) network using STRING 11.0. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed according to the DAVID bioinformatics resource database (ver. 6.8). We validated the predicted compound's efficacy using the experimental rat chronic constriction injury (CCI) model. The neuronal apoptosis was located using the TUNEL assay and the related pathways' hub proteins were determined by PCR, Western blot, and immunohistochemical staining.

Results: We identified 173 targets and 35 potential compounds belonging to XNJI. STRING analysis was used to illustrate the protein-protein interactions and show that muscone played a fundamental role in XNJI's efficacy. Enrichment analysis revealed critical signaling pathways in these components' potential protein targets, including PI3K/AKT1, NF-kB, and p53. Moreover, the hub proteins CASP3, BCL2L1, and CASP8 were also involved in apoptosis and were associated with PI3K/AKT, NF-kB, and p53 signaling pathways. We showed that muscone and XNJI were similarly effective 168 h after CCI, demonstrating that the muscone in XNJI significantly attenuated neuronal apoptosis through the PI3K/Akt1/NF-kB/P53 pathway.

Conclusion: We verified the neuroprotective mechanism in muscone for the first time in TBI. Network pharmacology offers a new approach for identifying the potential active ingredients in XNJI.
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http://dx.doi.org/10.7717/peerj.11696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300495PMC
July 2021

Magnetic anisotropy and critical behavior of the quaternary van der Waals ferromagnetic material CrGeSiTe.

J Phys Condens Matter 2021 Aug 11;33(42). Epub 2021 Aug 11.

Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.

Recently, two-dimensional ferromagnetism in the family of chromium compounds CrTe(= Si, Ge) has attracted a broad research interest. Despite the structural similarity in CrTeoctahedra, the size effect of inserted Ge or Si dimer contributes to significant differences in magnetism. Here, we report a new family of quaternary van der Waals ferromagnetic material CrGeSiTe(< 0.2) synthesized by flux method. Ge substitution in Si site results in the lattice expansion, further increasing the Curie temperature and reducing the magnetic anisotropy. The critical behavior of CrGeSiTehas been studied by specific heat as well as magnetization measurements. And the extracted critical exponents are self-consistent and well-obeying the scaling laws, which are closer to the 2D Ising model with interaction decaying as() ≈.
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http://dx.doi.org/10.1088/1361-648X/ac1882DOI Listing
August 2021

Strategy for Nontargeted Metabolomic Annotation and Quantitation Using a High-Resolution Spectral-Stitching Nanoelectrospray Direct-Infusion Mass Spectrometry with Data-Independent Acquisition.

Anal Chem 2021 08 22;93(30):10528-10537. Epub 2021 Jul 22.

CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China.

Direct-infusion nanoelectrospray ionization high-resolution mass spectrometry (DI-nESI-HRMS) is an alternative approach to chromatography-MS-based techniques for nontargeted metabolomics, offering a high sample throughout. However, its annotation accuracy of analytes is still full of challenges. In this study, we proposed a strategy for the annotation and quantitation of nontargeted metabolomic data using a spectral-stitching DI-nESI-HRMS with data-independent acquisition. The metabolite annotation strategy included the isotopic distribution, MS/MS spectrum similarity, and precursor and product ion correlation as well as matching of the extracted metabolite features along with the targeted metabolite precursors. Two groups of mixed standard solutions containing 40 and 79 metabolites were, respectively, used to establish the metabolite annotation strategy and validate its reliability. The results showed that the detected standards could be well annotated at top three explanations and total qualitative percentages were 100% (40 of 40) for the standard solution and 94.9% (74 of 78) for the standards spiked into the serum matrix. The intensity of the precursor ions was used for quantitation except for isomers, which were quantified by the intensities of the characteristic product ions if available. Finally, the strategy was applied to study serum metabolomics in diabetes, and the results demonstrated that it is promising for a large-scale cohort metabolomic study.
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http://dx.doi.org/10.1021/acs.analchem.1c01480DOI Listing
August 2021

Relationships between the Physicochemical Properties of Dissolved Organic Matter and Its Reaction with Sodium Borohydride.

Environ Sci Technol 2021 08 22;55(15):10843-10851. Epub 2021 Jul 22.

Zachry Department of Civil & Environmental Engineering, Texas A&M University, College Station, Texas 77845, United States.

The reaction of dissolved organic matter (DOM) with sodium borohydride has been used to understand the geographic origin of DOM and investigate the photophysical model underlying DOM's optical properties. However, the physicochemical properties of DOM (e.g., molecular size and charge) that influence the kinetics and ultimate reducibility of DOM by borohydride remain poorly characterized. Herein, we studied the kinetics of DOM-borohydride reactions by recording absorbance and fluorescence spectra at a high temporal frequency (every ∼10 min for 24 h) for a diverse set of DOM isolates of aquatic and soil origin. The reducibility of DOM by sodium borohydride (as judged by relative removal of initial absorbance) varied appreciably among the DOM samples studied, with soil humic substances being less reducible than aquatic humic substances and natural organic matter. While statistically significant correlations were found between the reducibility of DOM and descriptors of molecular size, these descriptors were not able to differentiate the reducibility of soil versus aquatic DOM isolates that had similar bulk properties. Thus, it appears that the extent of absorbance removal by borohydride is largely driven by the origin of the humic substance isolate (aquatic vs soil) instead of molecular size or charge. Borohydride reduction resulted in increased fluorescence emission across UV and visible excitation wavelengths. However, the enhanced emission at visible excitation decreased over a time period of hours to days, suggesting that reduction of an important subset of DOM chromophores is reversible. This reversibility in fluorescence emission is consistent with the small role of quinones in the absorbance of DOM but suggests a more important role for quinone-containing charge-transfer contacts in the fluorescence of DOM, particularly at visible excitation wavelengths.
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http://dx.doi.org/10.1021/acs.est.1c01973DOI Listing
August 2021

Efficacy and safety of neoadjuvant chemotherapy and immunotherapy in locally resectable advanced esophageal squamous cell carcinoma.

J Thorac Dis 2021 Jun;13(6):3518-3528

Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

Background: Esophageal squamous cell cancer (ESCC) patients with the potentially resectable disease most would experience relapse after surgery. Immunotherapy has been reported to improve the prognosis of advanced esophageal cancer and may be a new strategy to prevent this urgent condition's recurrence. We first evaluated the efficacy and safety of neoadjuvant chemotherapy combined with immunotherapy in patients with resectable ESCC.

Methods: All patients with resectable locally advanced ESCC (clinical stage III-IVB). Received at least 1 cycle of neoadjuvant chemotherapy combined with immunotherapy (NACI), and the interval between each cycle and the operation should be at least 3 weeks. All patients were treated with standard surgery. The tumor imaginations were obtained at baseline and within a week before surgery. The efficacy endpoint was the rate of major pathologic response (MPR, 10% viable tumor cells). Expression of immunohistochemical-related molecules was investigated in surgical samples.

Results: A total of 38 patients with ESCC were included (36 males, median age 61 years), and most of them used Pembrolizumab (55.26%) and Camrelizumab (31.58%). We analyzed 19 patients and found that 13 patients (68.42%) achieved radiological partial response (PR) by CT images. R0 resection was performed in 35 patients (92.11%), and 10 patients (26.32%) developed postoperative complications. Through postoperative pathology, we found 13 (34.21%) patients had complete pathologic response (cPR), and 16 (42.11%) patients achieved MPR. We also found that none of the factors had a statistically significant impact on MPR. Still, the regression rate of Sum of lesion diameter (SLD) was significantly positively correlated with the pathological remission rate (P=0.012, r=0.565).

Conclusions: The rate of MPR in ESCC patients reached 42.11%. The use of the NACI regimen did not increase the occurrence of complications in neoadjuvant treatment and operation, and the SLD regression rate has a certain guiding significance for the effect of immunotherapy.
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http://dx.doi.org/10.21037/jtd-21-340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264718PMC
June 2021

Discovery and Validation of Key Biomarkers Based on Immune Infiltrates in Alzheimer's Disease.

Front Genet 2021 1;12:658323. Epub 2021 Jul 1.

The Fifth Clinical Medical College of Anhui Medical University, Beijing, China.

Background: As the most common neurodegenerative disease, Alzheimer's disease (AD) leads to progressive loss of cognition and memory. Presently, the underlying pathogenic genes of AD patients remain elusive, and effective disease-modifying therapy is not available. This study explored novel biomarkers that can affect diagnosis and treatment in AD based on immune infiltration.

Methods: The gene expression profiles of 139 AD cases and 134 normal controls were obtained from the NCBI GEO public database. We applied the computational method CIBERSORT to bulk gene expression profiles of AD to quantify 22 subsets of immune cells. Besides, based on the use of the Least Absolute Shrinkage Selection Operator (LASSO), this study also applied SVM-RFE analysis to screen key genes. GO-based semantic similarity and logistic regression model analyses were applied to explore hub genes further.

Results: There was a remarkable significance in the infiltration of immune cells between the subgroups. The proportions for monocytes, M0 macrophages, and dendritic cells in the AD group were significantly higher than those in the normal group, while the proportion of some cells was lower than that of the normal group, such as NK cell resting, T-cell CD4 naive, T-cell CD4 memory activation, and eosinophils. Additionally, seven genes (ABCA2, CREBRF, CD72, CETN2, KCNG1, NDUFA2, and RPL36AL) were identified as hub genes. Then we performed the analysis of immune factor correlation, gene set enrichment analysis (GSEA), and GO based on seven hub genes. The AUC of ROC prediction model in test and validation sets were 0.845 and 0.839, respectively. Eventually, the mRNA expression analysis of ABCA2, NDUFA2, CREBRF, and CD72 revealed significant differences among the seven hub genes and then was confirmed by RT-PCR.

Conclusion: A model based on immune cell infiltration might be used to forecast AD patients' diagnosis, and it provided a new perspective for AD treatment targets.
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http://dx.doi.org/10.3389/fgene.2021.658323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281057PMC
July 2021

Circular RNA EGLN3 silencing represses renal cell carcinoma progression through the miR-1224-3p/HMGXB3 axis.

Acta Histochem 2021 Sep 15;123(6):151752. Epub 2021 Jul 15.

Department of Urinary Surgery, Hanzhong People's Hospital, Hanzhong, Shaanxi, 723000, China. Electronic address:

Background: Renal cell carcinoma (RCC) is a common tumor of the urinary system, and its global incidence is increasing annually. Circular RNAs (circRNAs) are involved in RCC tumorigenesis; however, the role of circ-EGLN3 (hsa_circ_0031594) derived from the Egl nine homolog 3 (EGLN3) gene in RCC remains undetermined.

Methods: Circ-EGNL3 expression was examined before and after RNase R and actinomycin treatments in RCC cells and tissues. Cell proliferation, migration, and invasion were assessed using the CCK-8 assay, EdU staining, and wound-healing and Transwell assays. The interactions between microRNA (miR)-1224-3p and circ-EGLN3, and between miR-1224-3p and HMG box domain containing 3 (HMGXB3) were predicted by bioinformatics analysis and validated by dual-luciferase reporter assay.

Results: Circ-EGLN3 was identified using RNase R and actinomycin treatments. Circ-EGLN3 was upregulated in RCC cells and tissues and correlated with poor overall survival. Silencing of circ-EGNL3 decreased RCC cell proliferation, migration, and invasion. Mechanistic studies indicated that circ-EGNL3 acts as a sponge for miR-1224-3p, which targeted HMGXB3. Circ-EGNL3 indirectly upregulated HMGXB3 by targeting miR-1224-3p, and overexpression of circ-EGLN3 reversed the repressive effects of miR-1224-3p on RCC.

Conclusion: Circ-EGLN3 regulated RCC progression through the miR-1224-3p/HMGXB3 axis, suggesting its potential as a therapeutic target.
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http://dx.doi.org/10.1016/j.acthis.2021.151752DOI Listing
September 2021

Lipid Profiling of 20 Mammalian Cells by Capillary Microsampling Combined with High-Resolution Spectral Stitching Nanoelectrospray Ionization Direct-Infusion Mass Spectrometry.

Anal Chem 2021 07 16;93(29):10031-10038. Epub 2021 Jul 16.

CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.

Studies of cellular metabolism can provide profound insights into the underlying molecular mechanisms and metabolic function. To date, the majority of cellular metabolism studies based on chromatography-mass spectrometry (MS) require population cells to obtain informative metabolome. These methods are not only time-consuming but also not suitable for amount-limited cell samples such as circulating tumor cells, stem cells, and neurons. Therefore, it is extremely essential to develop analytical methods enabling to detect metabolome from tens of cells in a high-throughput and high-sensitivity way. In this work, a novel platform for rapid and sensitive detection of lipidome in 20 mammalian cells was proposed using capillary microsampling combined with high-resolution spectral stitching nanoelectrospray ionization direct-infusion MS. It can be used to collect cells rapidly and accurately via the capillary microprobe, extract lipids directly in a 96-well plate using a spray solvent, and detect more than 500 lipids covering 19 lipid subclasses within 3 min. This novel platform was successfully applied to study the lipid features of different cancer cell types and subtypes as well as target cells from tissue samples. This study provides a strategy for determining the lipid species with rich information in tens of cells and demonstrates great potential for clinical applications.
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http://dx.doi.org/10.1021/acs.analchem.1c00373DOI Listing
July 2021

Interventional Treatment for Cholangiocarcinoma.

Front Oncol 2021 29;11:671327. Epub 2021 Jun 29.

Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.

Cholangiocarcinoma (CCA) is the second most common type of primary liver malignancy. The latest classification includes intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma, with the latter one further categorized into perihilar and distal cholangiocarcinoma. Although surgical resection is the preferred treatment for CCA, less than half of the patients are actually eligible for radical surgical resection. Interventional treatment, such as intra-arterial therapies, ablation, and brachytherapy (iodine-125 seed implantation), has become an acceptable palliative treatment for patients with unresectable CCA. For these patients, interventional treatment is helpful for locoregional control, symptom relief, and improving quality of life. Herein, in a timely and topical manner, we will review these advances and highlight future directions of research in this article.
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http://dx.doi.org/10.3389/fonc.2021.671327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276166PMC
June 2021

Circulating white blood cells and lung function impairment: the observational studies and Mendelian randomization analysis.

Ann Med 2021 12;53(1):1118-1128

Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Circulating white blood cell (WBC) counts have been related to lung function impairment, but causal relationship was not established. We aimed to evaluate independent effects and causal relationships of WBC subtypes with lung function.

Methods: The 19,159 participants from NHANES 2011-2012 ( = 3570), coke-oven workers (COW,  = 1762) and Dongfeng-Tongji (DFTJ,  = 13,827) cohorts were included in the observational studies. The associations between circulating counts of WBC subtypes and prebronchodilator lung function were evaluated by linear regression models and LASSO regression was used to select effective WBC subtypes. Summary statistics for WBC-associated SNPs were extracted from literature, and Mendelian randomization (MR) analysis with inverse-variance weighted (IVW) method was applied to estimate the causal effects of total WBC and subtypes on lung function among 4012 subjects from COW ( = 1126) and DFTJ cohorts ( = 2886).

Results: Total WBC counts were negatively associated with lung function among three populations and their pooled analysis indicated that per 1 × 10 cells/L increase in total WBC was associated with 36.13 (95% CI: 30.35, 41.91) mL and 25.23 (95% CI: 19.97, 30.50) mL decrease in FVC and FEV, respectively. Independent associations with lung function were found for neutrophils, monocytes, eosinophils and basophils (all  < .05), except lymphocytes. Besides, IVW MR analysis showed that genetically predicted total WBC and neutrophil counts were associated with reduced FVC ( = .017 and .021, respectively) and FEV ( = .048 and .043, respectively).

Conclusions: WBC subtypes were independently associated with lower lung function except lymphocytes. Our findings suggest that circulating neutrophils may be causal factors in lung function impairment.KEY MESSAGESWhite blood cell (WBC) subtypes were negatively associated with lung function level except lymphocytes in the observational studies.Associations of WBC subtypes with lung function may be modified by sex and smoking.Mendelian randomization analysis shows that neutrophils may be causal factors in lung function impairment.
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http://dx.doi.org/10.1080/07853890.2021.1948603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280897PMC
December 2021

Corrigendum: CGRP Regulates the Age-Related Switch Between Osteoblast and Adipocyte Differentiation.

Front Cell Dev Biol 2021 22;9:715740. Epub 2021 Jun 22.

Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, China.

[This corrects the article DOI: 10.3389/fcell.2021.675503.].
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http://dx.doi.org/10.3389/fcell.2021.715740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259016PMC
June 2021
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