Publications by authors named "Han Cao"

130 Publications

Effects of Varicella-Zoster Virus Glycoprotein E Carboxyl-Terminal Mutation on mRNA Vaccine Efficacy.

Vaccines (Basel) 2021 Dec 7;9(12). Epub 2021 Dec 7.

Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China.

Glycoprotein E (gE) is one of the most abundant glycoproteins in varicella-zoster virus and plays pivotal roles in virus replication and transmission between ganglia cells. Its extracellular domain has been successfully used as an antigen in subunit zoster vaccines. The intracellular C-terminal domain was reported to be decisive for gE trafficking between the endoplasmic reticulum, trans-Golgi network and endosomes and could influence virus spread and virus titers. Considering that the trafficking and distribution of mRNA vaccine-translated gE may be different from those of gE translated against the background of the viral genome (e.g., most gE in virus-infected cells exists as heterodimers with another glycoprotein, gI,), which may influence the immunogenicity of gE-based mRNA vaccines, we compared the humoral and cellular immunity induced by LNP-encapsulated mRNA sequences encoding the whole length of gE, the extracellular domain of gE and a C-terminal double mutant of gE (mutant Y569A with original motif AYRV, which targets gE to TGN, and mutants S593A, S595A, T596A and T598A with the original motif SSTT) that were reported to enhance virus spread and elevate virus titers. The results showed that while the humoral and cellular immunity induced by all of the mRNA vaccines was comparable to or better than that induced by the AS01B-adjuvanted subunit vaccines, the C-terminal double mutant of gE showed stable advantages in all of the indicators tested, including gE-specific IgG titers and T cell responses, and could be adopted as a candidate for both safer varicella vaccines and effective zoster vaccines.
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http://dx.doi.org/10.3390/vaccines9121440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704662PMC
December 2021

Spin-Orbit Mapping of Light.

Phys Rev Lett 2021 Dec;127(23):233901

Wuhan National Laboratory for Optoelectronics and School of Optical and Electronic Information, Huazhong University of Science and Technology, Wuhan 430074, Hubei, China.

Spin-orbit photonics, involving the interaction between the spin angular momentum (SAM) and orbital angular momentum (OAM) of light, plays an important role in modern optics. Here, we present the spin-orbit mapping of light in a few-mode fiber that originates from the mode degeneracy lifting (TM_{01} and TE_{01}) property. We demonstrate two kinds of spin-orbit mapping phenomena, i.e., mapping from intrinsic SAM to OAM and mapping from polarization direction rotation to field pattern rotation. The demonstrated spin-orbit mapping shows high efficiency, large bandwidth, availability for short pulses, and scalability to high-order OAM states.
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http://dx.doi.org/10.1103/PhysRevLett.127.233901DOI Listing
December 2021

From Impossible to Possible: Atom-Economic Polymerization of Low Strain Five-Membered Carbonates.

Angew Chem Int Ed Engl 2021 Dec 1. Epub 2021 Dec 1.

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, CAS, Changchun, 130022, P. R. China.

The direct ring-opening polymerization (ROP) of propylene carbonate (PC) only affords oligomers with substantial unidentified by-products, which hinders the efficient utilization of PC. Through detailed studies, for the first time, a careful mechanism involving the in situ release of propylene oxide (PO) from PC decarboxylation is proposed. Further, we report a novel strategy of copolymerization of PC/cyclic anhydrides via in situ capture of the formed intermediates. Results show that PC is successfully transformed into polyesters. Especially for the ring-opening alternating copolymerization (ROAC) of PC/phthalic anhydride (PA), a variety of advantages are manifold: i) slow-release of PO ensuring a perfectly alternating structure; ii) quantitative and fast transformation of PC; iii) visualization of polymerization process by a CO pressure gauge. Of importance, through tandem polymerizations, PC is fully transformed into polyesters and polycarbonates concurrently, thus achieving PC utilization with a high atom-economy.
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http://dx.doi.org/10.1002/anie.202113152DOI Listing
December 2021

Association of Circulating Biomarkers of lnc-IGSF3-1:1, SCOC-AS1, and SLC8A1-AS1 with Salt Sensitivity of Blood Pressure in Chinese Population.

J Cardiovasc Transl Res 2021 Dec 2. Epub 2021 Dec 2.

Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, No. 10, Xi Toutiao You Anmenwai, Fengtai District, Beijing, 100069, China.

Accumulating evidence suggested that long non-coding RNAs (lncRNAs) could play biological roles in cardiovascular diseases. We investigated whether lncRNAs can serve as biomarkers for salt sensitivity of blood pressure (SSBP). Participants were divided into salt-sensitive (SS) and salt-resistant (SR) ones by oral saline test. LncRNAs were tested by microarray (N = 20) and two-stage qRT-PCR (N = 89 and 228). We identified five differently expressed lncRNAs (lnc-IGSF3-1:1, SCOC-AS1, SLC8A1-AS1, KCNQ1OT1, and lnc-GNG-10-3:1) between SS and SR. In single-lncRNA analyses, lnc-IGSF3-1:1 displayed better diagnostic performance in hypertensive patients (AUC = 0.840), while SCOC-AS1 in normotensive (AUC = 0.810). In multi-lncRNA analyses, lnc-IGSF3-1:1 + SCOC-AS1 + SLC8A1-AS1 combination showed the best diagnostic performance in hypertensive (AUC = 0.853) and normotensive groups (AUC = 0.873). We constructed a lncRNA-mRNA-GO-KEGG-disease network by bioinformatic analysis; lnc-IGSF3-1:1 and SLC8A1-AS1 were identified as hub biomarkers. Our findings suggest that lnc-IGSF3-1:1, SCOC-AS1, and SLC8A1-AS1 may represent as genetic susceptible biomarkers for SSBP, and had different SS diagnostic performance in hypertensive patients and normotensive individuals.
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http://dx.doi.org/10.1007/s12265-021-10190-0DOI Listing
December 2021

An Established Th2-Oriented Response to an Alum-Adjuvanted SARS-CoV-2 Subunit Vaccine Is Not Reversible by Sequential Immunization with Nucleic Acid-Adjuvanted Th1-Oriented Subunit Vaccines.

Vaccines (Basel) 2021 Nov 1;9(11). Epub 2021 Nov 1.

Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China.

A recently reported parallel preclinical study between a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine and an inactivated SARS-CoV-2 vaccine adjuvanted with alum showed pulmonary immunopathology typical of eosinophil accumulation in a mouse pneumonia model for the latter, which implied a potential role of cellular immunity in the difference in the protection rate between these two forms of vaccines. For those who have been vaccinated with alum-adjuvanted subunit or inactivated SARS-CoV-2 vaccines, whether the Th2 responses that have been established and the absence of induced cellular immunity could be changed is an open question. Using two heterologous boosts with Th1-oriented CpG ODN-adjuvanted S1-based SARS-CoV-2 subunit vaccines for mice that were primed with two doses of Th2-oriented alum-adjuvanted S1-based SARS-CoV-2 subunit vaccines, we demonstrated that established Th2 orientation could not be reversed to Th1 orientation and that no cellular immunity was induced, which should have been induced if the boosting vaccines were used as the prime vaccines. These results remind us that if widely administered alum-adjuvanted SARS-CoV-2 vaccines cannot overcome the challenge of coronavirus disease 2019 (COVID-19) and that if cellular immunity is important for the efficacy of SARS-CoV-2 vaccines in the future, the choice of more powerful heterologous boosting vaccine forms that can induce cellular immunity should be considered very carefully before application.
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http://dx.doi.org/10.3390/vaccines9111261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8617830PMC
November 2021

Associations of Ambient Air Pollutants and Meteorological Factors With COVID-19 Transmission in 31 Chinese Provinces: A Time Series Study.

Inquiry 2021 Jan-Dec;58:469580211060259

Department of Epidemiology and Health Statistics, School of Public Health, 379397Capital Medical University, and Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China.

Evidence regarding the effects of environmental factors on COVID-19 transmission is mixed. We aimed to explore the associations of air pollutants and meteorological factors with COVID-19 confirmed cases during the outbreak period throughout China. The number of COVID-19 confirmed cases, air pollutant concentrations, and meteorological factors in China from January 25 to February 29, 2020, (36 days) were extracted from authoritative electronic databases. The associations were estimated for a single-day lag as well as moving averages lag using generalized additive mixed models. Region-specific analyses and meta-analysis were conducted in 5 selected regions from the north to south of China with diverse air pollution levels and weather conditions and sufficient sample size. Nonlinear concentration-response analyses were performed. An increase of each interquartile range in PM, PM, SO, NO, O, and CO at lag4 corresponded to 1.40 (1.37-1.43), 1.35 (1.32-1.37), 1.01 (1.00-1.02), 1.08 (1.07-1.10), 1.28 (1.27-1.29), and 1.26 (1.24-1.28) ORs of daily new cases, respectively. For 1°C, 1%, and 1 m/s increase in temperature, relative humidity, and wind velocity, the ORs were 0.97 (0.97-0.98), 0.96 (0.96-0.97), and 0.94 (0.92-0.95), respectively. The estimates of PM, PM, NO, and all meteorological factors remained significantly after meta-analysis for the five selected regions. The concentration-response relationships showed that higher concentrations of air pollutants and lower meteorological factors were associated with daily new cases increasing. Higher air pollutant concentrations and lower temperature, relative humidity and wind velocity may favor COVID-19 transmission. Controlling ambient air pollution, especially for PM, PM, NO, may be an important component of reducing risk of COVID-19 infection. In addition, as winter months are arriving in China, the meteorological factors may play a negative role in prevention. Therefore, it is significant to implement the public health control measures persistently in case another possible pandemic.
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http://dx.doi.org/10.1177/00469580211060259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8613882PMC
November 2021

Broadband decoupled spin and orbital angular momentum detection via programming dual-twist reactive mesogens.

Opt Lett 2021 Nov;46(22):5751-5754

The introduction of spin and orbital angular momentum mode division multiplexing to existing wavelength division multiplexing will significantly enlarge the capacity of optical networks. Therefore, components compatible with the above techniques are in high demand. Here, a geometric phase combined a Dammann vortex grating, and a polarization grating is designed and encoded to a dual-twist reactive mesogen. It can generate a couple of vortex channel arrays highly efficiently in broadband. Meanwhile, orthogonal spins are spatially separated, facilitating spin identification. A vortex will recover to a Gaussian beam when it is diffracted to an order with opposite topological charge, which enables the detection of orbital angular momentum. It supplies a parallel and efficient way for decoupled spin and orbital angular momentum detection operating at the entire visible range, and the design may be extended to many other compatible optical communication components.
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http://dx.doi.org/10.1364/OL.443894DOI Listing
November 2021

Long-term exposure to ambient nitrogen dioxide and ozone modifies systematic low-grade inflammation: The CHCN-BTH study.

Int J Hyg Environ Health 2022 Jan 29;239:113875. Epub 2021 Oct 29.

Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China. Electronic address:

The potential effect of long-term exposure to ambient air pollutants on low-grade systematic inflammation has seldom been evaluated taking indoor air pollution and self-protection behaviors on smog days into account. A total of 24,346 participants at baseline were included to conduct a cross-sectional study. The annual (2016) average pollutant concentrations were assessed by air monitoring stations for PM, PM, SO, NO, O and CO. Associations between annual ambient air pollution and low-grade systematic inflammation (hsCRP>3 mg/L) were estimated by generalized linear mixed models. Stratification analysis was also performed based on demographic characteristics, health-related behaviors and disease status. Annual ambient NO and O were all associated with low-grade systematic inflammation in single-pollutant models after adjusting for age, sex, blood lipids, blood pressure, lifestyle risk factors, cooking fuel, heating fuel and habits during smog days (NO per 10 μg/m: OR = 1.057, P = 0.018; O per 10 μg/m: OR = 0.953, P = 0.012). The 2-year and 3-year ozone concentrations were consistently associated with lower systematic inflammation (2-year O per 10 μg/m: OR = 0.959, P = 0.004; 3-year O per 10 μg/m: OR = 0.961, P = 0.014). In two-pollutant models, the estimated effects of annual NO and O on low-grade systematic inflammation remained stable. The effect size of annual pollutants on inflammation increased in participants without air-purifier usage (NO per 10 μg/m: OR = 1.079, P = 0.009; O per 10 μg/m: OR = 0.925, P = 0.001), while the association was null in the air-purifier usage group. Thus, long-term exposure to ambient NO and O was associated with low-grade systemic inflammation, and the results were generally stable after sensitivity analysis. The usage of air purifiers on smog days can modify the association between gaseous pollutants and systematic inflammation.
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http://dx.doi.org/10.1016/j.ijheh.2021.113875DOI Listing
January 2022

Waning antibodies from inactivated SARS-CoV-2 vaccination offer protection against infection without antibody-enhanced immunopathology in rhesus macaque pneumonia models.

Emerg Microbes Infect 2021 Dec;10(1):2194-2198

Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, People's Republic of China.

Inactivated coronaviruses, including severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and Middle East respiratory syndrome coronavirus (MERS-CoV), as potential vaccines have been reported to result in enhanced respiratory diseases (ERDs) in murine and nonhuman primate (NHP) pneumonia models after virus challenge, which poses great safety concerns of antibody-dependent enhancement (ADE) for the rapid wide application of inactivated SARS-CoV-2 vaccines in humans, especially when the neutralizing antibody levels induced by vaccination or initial infection quickly wane to nonneutralizing or subneutralizing levels over the time. With passive transfer of diluted postvaccination polyclonal antibodies to mimic the waning antibody responses after vaccination, we found that in the absence of cellular immunity, passive infusion of subneutralizing or nonneutralizing anti-SARS-CoV-2 antibodies could still provide some level of protection against infection upon challenge, and no low-level antibody-enhanced infection was observed. The anti-SARS-CoV-2 IgG-infused group and control group showed similar, mild to moderate pulmonary immunopathology during the acute phase of virus infection, and no evidence of vaccine-related pulmonary immunopathology enhancement was found. Typical immunopathology included elevated MCP-1, IL-8 and IL-33 in bronchoalveolar lavage fluid; alveolar epithelial hyperplasia; and exfoliated cells and mucus in bronchioles. Our results corresponded with the recent observations that no pulmonary immunology was detected in preclinical studies of inactivated SARS-CoV-2 vaccines in either murine or NHP pneumonia models or in large clinical trials and further supported the safety of inactivated SARS-CoV-2 vaccines.
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http://dx.doi.org/10.1080/22221751.2021.2002670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635581PMC
December 2021

Candidate Gene Polymorphisms Influence the Susceptibility to Salt Sensitivity of Blood Pressure in a Han Chinese Population: Risk Factors as Mediators.

Front Genet 2021 4;12:675230. Epub 2021 Oct 4.

Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China.

Genome-wide association studies suggest that there is a significant genetic susceptibility to salt sensitivity of blood pressure (SSBP), but it still needs to be verified in varied and large sample populations. We attempted to verify the associations between single-nucleotide polymorphisms (SNPs) in candidate genes and SSBP and to estimate their interaction with potential risk factors. A total of 29 candidate SNPs were genotyped in the 2,057 northern Han Chinese population from the Systems Epidemiology Study on Salt Sensitivity. A modified Sullivan's acute oral saline load and diuresis shrinkage test (MSAOSL-DST) was used to identify SSBP. A generalized linear model was conducted to analyze the association between SNPs and SSBP, and Bonferroni correction was used for multiple testing. Mediation analysis was utilized to explore the mediation effect of risk factors. Eleven SNPs in eight genes (PRKG1, CYBA, BCAT1, SLC8A1, AGTR1, SELE, CYP4A11, and VSNL1) were identified to be significantly associated with one or more SSBP phenotypes ( < 0.05). Four SNPs (PRKG1/rs1904694 and rs7897633, CYP4A11/rs1126742, and CYBA/rs4673) were still significantly associated after Bonferroni correction ( < 0.0007) adjusted for age, sex, fasting blood glucose, total cholesterol, salt-eating habit, physical activity, and hypertension. Stratified analysis showed that CYBA/rs4673 was significantly associated with SSBP in hypertensive subjects ( < 0.0015) and CYP4A11/rs1126742 was significantly associated with SSBP in normotensive subjects ( < 0.0015). Subjects carrying both CYBA/rs4673-AA and AGTR1/rs2638360-GG alleles have a higher genetic predisposition to salt sensitivity due to the potential gene co-expression interaction. Expression quantitative trait loci analysis (eQTL) suggested that the above positive four SNPs showed cis-eQTL effects on the gene expression levels. Mediation analysis suggested that several risk factors were mediators of the relation between SNP and SSBP. This study suggests that the genetic variants in eight genes might contribute to the susceptibility to SSBP, and other risk factors may be the mediators.
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http://dx.doi.org/10.3389/fgene.2021.675230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521039PMC
October 2021

Impact of lipoprotein(a) level on cardiometabolic disease in the Chinese population: The CHCN-BTH Study.

Eur J Clin Invest 2022 Feb 19;52(2):e13689. Epub 2021 Oct 19.

Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, and Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China.

Background: The emergence of promising compounds to lower lipoprotein(a) [Lp(a)] has increased the need for a precise characterisation and comparability assessment of Lp(a)-associated cardiometabolic disease risk. This study aimed to evaluate the distribution of Lp(a) levels in a Chinese population and characterise the association with cardiometabolic diseases.

Methods: We assessed data from individuals from the Cohort Study on Chronic Diseases of the General Community Population in the Beijing-Tianjin-Hebei Region project. All Lp(a) measurements were performed in the same hospital. The cardiometabolic diseases considered were coronary heart disease (CHD), stroke, hypertension and type 2 diabetes (T2DM).

Results: A total of 25343 individuals were included in the study. The median level of Lp(a) was 11.9 mg/dl (IQR 5.9 to 23.7 mg/dl), and higher Lp(a) levels showed a significant concentration-dependent association with CHD risk. Individuals with Lp(a) levels lower than the 25th percentile were at increased risk of hypertension (OR: 1.15, 95% CI: 1.06-1.25) and T2DM (OR: 1.15, 95% CI: 1.03-1.28); however, Lp(a) levels were not significantly associated with stroke. The addition of Lp(a) levels to the prognostic model led to a marginal but significant C-index, integrated discrimination improvement and net reclassification improvement.

Conclusions: In this large sample size study, we observed that elevated Lp(a) levels were significantly associated with CHD. Furthermore, we found that the lowest Lp(a) levels were also significantly associated with hypertension and T2DM. These results provide evidence for differential approaches to higher levels of Lp(a) in individuals with different cardiometabolic diseases.
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http://dx.doi.org/10.1111/eci.13689DOI Listing
February 2022

Pd-Catalyzed Double-Decarbonylative Aryl Sulfide Synthesis through Aryl Exchange between Amides and Thioesters.

Org Lett 2021 Oct 5;23(20):8098-8103. Epub 2021 Oct 5.

School of Chemistry and Materials Science, Nanjing University of Information Science and Technology, 219 Ningliu Road, Nanjing, Jiangsu 210044, China.

We report the palladium-catalyzed double-decarbonylative synthesis of aryl thioethers by an aryl exchange reaction between amides and thioesters. In this method, amides serve as aryl donors and thioesters are sulfide donors, enabling the synthesis of valuable aryl sulfides. The use of Pd/Xantphos without any additives has been identified as the catalytic system promoting the aryl exchange by C(O)-N/C(O)-S cleavages. The method is amenable to a wide variety of amides and sulfides.
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http://dx.doi.org/10.1021/acs.orglett.1c03232DOI Listing
October 2021

Ventral Striatal-Hippocampus Coupling During Reward Processing as a Stratification Biomarker for Psychotic Disorders.

Biol Psychiatry 2022 Jan 24;91(2):216-225. Epub 2021 Jul 24.

Systems Neuroscience in Psychiatry, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany. Electronic address:

Background: Altered ventral striatal (vST) activation to reward expectancy is a well-established intermediate phenotype for psychiatric disorders, specifically schizophrenia (SZ). Preclinical research suggests that striatal alterations are related to a reduced inhibition by the hippocampal formation, but its role in human transdiagnostic reward-network dysfunctions is not well understood.

Methods: We performed functional magnetic resonance imaging during reward processing in 728 individuals including healthy control subjects (n = 396), patients (SZ: n = 46; bipolar disorder: n = 45; major depressive disorder: n = 60), and unaffected first-degree relatives (SZ: n = 46; bipolar disorder: n = 50; major depressive disorder: n = 85). We assessed disorder-specific differences in functional vST-hippocampus coupling and transdiagnostic associations with dimensional measures of positive, negative, and cognitive symptoms. We also probed the genetic underpinning using polygenic risk scores for SZ in a subset of healthy participants (n = 295).

Results: Functional vST-hippocampus coupling was 1) reduced in patients with SZ and bipolar disorder (p < .05, small-volume corrected [SVC]); 2) associated transdiagnostically to dimensional measures of positive (p = .01, SVC) and cognitive (p = .02, SVC), but not negative, (p > .05, SVC) symptoms; and 3) reduced in first-degree relatives of patients with SZ (p = .017, SVC) and linked to the genetic risk for SZ in healthy participants (p = .035).

Conclusions: We provide evidence that reduced vST-hippocampus coupling during reward processing is an endophenotype for SZ linked to positive and cognitive symptoms, supporting current preclinical models of the emergence of psychosis. Moreover, our data indicate that vST-hippocampus coupling is familial and linked to polygenic scores for SZ, supporting the use of this measure as an intermediate phenotype for psychotic disorders.
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http://dx.doi.org/10.1016/j.biopsych.2021.07.016DOI Listing
January 2022

Differential resting-state patterns across networks are spatially associated with Comt and Trmt2a gene expression patterns in a mouse model of 22q11.2 deletion.

Neuroimage 2021 11 26;243:118520. Epub 2021 Aug 26.

Department of Neuroscience and Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA; Department of Neuroscience and Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA. Electronic address:

Copy number variations (CNV) involving multiple genes are ideal models to study polygenic neuropsychiatric disorders. Since 22q11.2 deletion is regarded as the most important single genetic risk factor for developing schizophrenia, characterizing the effects of this CNV on neural networks offers a unique avenue towards delineating polygenic interactions conferring risk for the disorder. We used a Df(h22q11)/+ mouse model of human 22q11.2 deletion to dissect gene expression patterns that would spatially overlap with differential resting-state functional connectivity (FC) patterns in this model (N = 12 Df(h22q11)/+ mice, N = 10 littermate controls). To confirm the translational relevance of our findings, we analyzed tissue samples from schizophrenia patients and healthy controls using machine learning to explore whether identified genes were co-expressed in humans. Additionally, we employed the STRING protein-protein interaction database to identify potential interactions between genes spatially associated with hypo- or hyper-FC. We found significant associations between differential resting-state connectivity and spatial gene expression patterns for both hypo- and hyper-FC. Two genes, Comt and Trmt2a, were consistently over-expressed across all networks. An analysis of human datasets pointed to a disrupted co-expression of these two genes in the brain in schizophrenia patients, but not in healthy controls. Our findings suggest that COMT and TRMT2A form a core genetic component implicated in differential resting-state connectivity patterns in the 22q11.2 deletion. A disruption of their co-expression in schizophrenia patients points out a prospective cause for the aberrance of brain networks communication in 22q11.2 deletion syndrome on a molecular level.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118520DOI Listing
November 2021

Rh(I)-Catalyzed Intramolecular Decarbonylation of Thioesters.

J Org Chem 2021 08 9;86(15):10829-10837. Epub 2021 Jul 9.

Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, United Kingdom.

Decarbonylative synthesis of thioethers from thioesters proceeds in the presence of a catalytic amount of [Rh(cod)Cl] (2 mol %). The protocol represents the first Rh-catalyzed decarbonylative thioetherification of thioesters to yield valuable thioethers. Notable features include the absence of phosphine ligands, inorganic bases, and other additives and excellent group tolerance to aryl chlorides and bromides that are problematic using other metals to promote decarbonylation. Gram scale synthesis, late-stage pharmaceutical derivatization, and orthogonal site-selective cross-couplings by C-S/C-Br cleavage are reported.
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http://dx.doi.org/10.1021/acs.joc.1c01117DOI Listing
August 2021

Environmental and Genetic Determinants of Major Chronic Disease in Beijing-Tianjin-Hebei Region: Protocol for a Community-Based Cohort Study.

Front Public Health 2021 4;9:659701. Epub 2021 Jun 4.

Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China.

Personal lifestyle and air pollution are potential risk factors for major non-communicable diseases (NCDs). However, these risk factors have experienced dramatic changes in the Beijing-Tianjin-Hebei (BTH) region in recent years, and few cohorts have focused on identifying risk factors for major NCDs in this specific region. The current study is a large, prospective, long-term, population-based cohort study that investigated environmental and genetic determinants of NCDs in BTH areas. The results of this study may provide scientific support for efforts to develop health recommendations for personalized prevention. About 36,000 participants 18 years or older would be obtained by multistage, stratified cluster sampling from five cities for the baseline assessment. Participants underwent seven examinations primarily targeting respiratory and circulatory system function and filled out questionnaires regarding lifestyle behavior, pollutant exposure, medical and family history, medication history, and psychological factors. Biochemistry indicators and inflammation markers were tested, and a biobank was established. Participants will be followed up every 2 years. Genetic determinants of NCDs will be demonstrated by using multiomics, and risk prediction models will be constructed using machine learning methods based on a multitude of environmental exposure, examination data, biomarkers, and psychosocial and behavioral assessments. Significant spatial and temporal differentiation is well-suited to demonstrating the health determinants of NCDs in the BTH region, which may facilitate public health strategies with respect to disease prevention and survivorship-related aspects.
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http://dx.doi.org/10.3389/fpubh.2021.659701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212971PMC
August 2021

Association study of fasting blood glucose and salt sensitivity of blood pressure in community population: The EpiSS study.

Nutr Metab Cardiovasc Dis 2021 07 8;31(8):2366-2375. Epub 2021 May 8.

Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, and Beijing Municipal Key Laboratory of Clinical Epidemiology Beijing, 100069, China. Electronic address:

Background And Aims: To evaluate the association between fasting blood glucose (FBG) and salt sensitivity of blood pressure (SSBP).

Methods And Results: This study is based on the baseline survey of systemic epidemiology of salt sensitivity study. Subjects were classified into salt sensitive (SS) and salt resistant groups according to blood pressure (BP) changes during the modified Sullivan's acute oral saline load and diuresis shrinkage test. Multivariate logistic and linear regression were used to evaluate associations between FBG with SS or BP changes. A total of 2051 participants were included in the analyses with 581 (28.33%) for SS. Multiple analysis showed that for every interquartile range increase in FBG, the OR (95%CI) for SS was 1.140 (1.069, 1.215), β (95%CI) for mean arterial pressure change (ΔMAP), systolic and diastolic BP changes during saline load were 0.421 (0.221, 0.622), 0.589 (0.263, 0.914) and 0.340 (0.149, 0.531), respectively. Compared to the lowest FBG quartile (Q), the OR (95%CI) for SS in Q and Q were 1.342 (1.014, 1.776) and 1.577 (1.194, 2.084), respectively. Compared to subjects with normal FBG, the β (95%CI) for ΔMAP was 0.973 (0.055, 1.891) in subjects with impaired FBG, and was 1.449 (0.602, 2.296) in patients with diabetes mellitus. Stratified analyses showed significant and stronger associations between FBG with SSBP in youngers, females, hypertensives, non-diabetics, non-current smokers and non-current drinkers.

Conclusion: Our findings suggest FBG is an independent, dose-dependent associated factor for SSBP, and prevention of SS focusing on controlling FBG elevation in the early stage is important.
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http://dx.doi.org/10.1016/j.numecd.2021.04.026DOI Listing
July 2021

Association of Lipoprotein (a) variants with risk of cardiovascular disease: a Mendelian randomization study.

Lipids Health Dis 2021 Jun 1;20(1):57. Epub 2021 Jun 1.

Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University and Beijing Municipal Key Laboratory of Clinical Epidemiology, No 10 Xitoutiao, You'anmenwai, Fengtai, Beijing, 100069, P. R. China.

Background: There is a well-documented empirical relationship between lipoprotein (a) [Lp(a)] and cardiovascular disease (CVD); however, causal evidence, especially from the Chinese population, is lacking. Therefore, this study aims to estimate the causal association between variants in genes affecting Lp(a) concentrations and CVD in people of Han Chinese ethnicity.

Methods: Two-sample Mendelian randomization analysis was used to assess the causal effect of Lp(a) concentrations on the risk of CVD. Summary statistics for Lp(a) variants were obtained from 1256 individuals in the Cohort Study on Chronic Disease of Communities Natural Population in Beijing, Tianjin and Hebei. Data on associations between single-nucleotide polymorphisms (SNPs) and CVD were obtained from recently published genome-wide association studies.

Results: Thirteen SNPs associated with Lp(a) levels in the Han Chinese population were used as instrumental variables. Genetically elevated Lp(a) was inversely associated with the risk of atrial fibrillation [odds ratio (OR), 0.94; 95% confidence interval (95%CI), 0.901-0.987; P = 0.012)], the risk of arrhythmia (OR, 0.96; 95%CI, 0.941-0.990; P = 0.005), the left ventricular mass index (OR, 0.97; 95%CI, 0.949-1.000; P = 0.048), and the left ventricular internal dimension in diastole (OR, 0.97; 95%CI, 0.950-0.997; P = 0.028) according to the inverse-variance weighted method. No significant association was observed for congestive heart failure (OR, 0.99; 95% CI, 0.950-1.038; P = 0.766), ischemic stroke (OR, 1.01; 95%CI, 0.981-1.046; P = 0.422), and left ventricular internal dimension in systole (OR, 0.98; 95%CI, 0.960-1.009; P = 0.214).

Conclusions: This study provided evidence that genetically elevated Lp(a) was inversely associated with atrial fibrillation, arrhythmia, the left ventricular mass index and the left ventricular internal dimension in diastole, but not with congestive heart failure, ischemic stroke, and the left ventricular internal dimension in systole in the Han Chinese population. Further research is needed to identify the mechanism underlying these results and determine whether genetically elevated Lp(a) increases the risk of coronary heart disease or other CVD subtypes.
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http://dx.doi.org/10.1186/s12944-021-01482-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170931PMC
June 2021

Association of long-term exposure to ambient particulate pollution with stage 1 hypertension defined by the 2017 ACC/AHA Hypertension Guideline and cardiovascular disease: The CHCN-BTH cohort study.

Environ Res 2021 08 26;199:111356. Epub 2021 May 26.

Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, And Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China. Electronic address:

Background: Evidence regarding the effects of ambient air pollution on new stage 1 hypertension defined by the 2017 ACC/AHA Hypertension Guideline remains sparse.

Objectives: To investigate the association of long-term exposure to ambient PM with stage 1 hypertension and to explore the mediating and modifying effects of PM on cardiovascular disease (CVD).

Methods: A total of 32,135 participants aged 18-80 years were recruited in 2017. The three-year (2014-2016) average PM concentrations were assessed by a spatial statistical model. Blood pressure (BP) was divided into four categories according to the 2017 ACC/AHA Hypertension Guideline: normal BP (SBP<120 mmHg and DBP<80 mmHg), elevated BP (SBP 120-129 mmHg and DBP<80 mmHg), stage 1 hypertension (SBP 130-139 mmHg or DBP 80-89 mmHg), and stage 2 hypertension (SBP≥140 mmHg or DBP≥90 mmHg or taking antihypertensive medications). The associations of PM with BP categories were estimated by two-level generalized linear mixed models. Analyses stratified by age, mediation and interaction analyses of PM and stage 1 hypertension with CVD were performed.

Results: We detected a positive significant association between long-term exposure to PM and stage 1 hypertension. Compared to normal BP, the OR was 1.05 (95% CI: 1.02, 1.08) per 10 μg/m increase in PM. The association was stronger than that of elevated BP but weaker than that of stage 2 hypertension. Stage 1 hypertension only partially mediated the association between PM and CVD, and the mediation proportions ranged from 1.55% to 11.00%. However, it modified the association between PM and CVD, which was greater in participants with stage 1 hypertension (OR: 1.66; 95% CI: 1.43, 1.93) than in participants with normal BP (OR: 1.32; 95% CI: 1.11, 1.57), with P<0.001. In the analysis stratified by age, the above associations were age-specific, and significant associations were only observed in the young and middle-aged (<60 years) groups.

Conclusions: Long-term exposure to ambient PM was significantly associated with stage 1 hypertension. This earlier stage of hypertension may be a trigger BP range for adverse effects of air pollution in the development of hypertension and CVD, especially in young and middle-aged individuals.
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http://dx.doi.org/10.1016/j.envres.2021.111356DOI Listing
August 2021

[email protected]@TiO nanocomposite based magnetic solid phase extraction coupled with LC-MS/MS for determination of lysophosphatidylcholines biomarkers of plasma in psoriasis patients.

J Pharm Biomed Anal 2021 Jul 1;201:114101. Epub 2021 May 1.

Pharmaceutical Analysis Department, School of Pharmacy, Fudan University, Shanghai 201203, Pudong, China. Electronic address:

Lysophosphatidylcholine (LPC) was commonly known as a class of significant differential metabolites of high relevance with many diseases including psoriasis, of which the accurate determination is of great importance to diagnosis or prediction to many diseases. However, it is challenging and complicated because of the enormous biological sample complexity and impurities interference. In this study, we synthesized a magnetic nanocomposite [email protected]@TiO and took advantage of the interactions of Lewis acid-base between the phosphate groups in LPCs and Ti ions on [email protected]@TiO nanomaterials for selective separation and enrichment of LPCs from complex biological matrix. The solid-phase extraction sample pretreatment process by means of [email protected]@TiO nanomaterials coupled with LC-MS/MS method was then applied to actual determination of six typical LPCs (LPC 10:0, 14:0, 16:0, 18:0, 18:1, 22:0) in human plasma. The extraction conditions were scientifically optimized by single-factor test (adsorbent amount, adsorption and desorption time, elution solvent type, eluant volume). Under the optimal conditions, the detection limits (LOD, S/N = 3) and quantification limits (LOQ, S/N = 10) were 1 and 5 ng/mL for LPC 10:0 and LPC 14:0, 0.02 and 0.1 ng/mL for LPC 16:0 and LPC 18:1, 0.05 and 0.2 ng/mL LPC 18:0 and LPC 22:0, respectively. The intra- and inter-day precisions were 3.82-12.60 % (n = 6) and 3.29-13.50 % (n = 6) respectively, the recoveries were in the range of 91.92-113.69 % and the stability of the analytes in the matrix performed well with RSDs≤15.51 %. Finally, the developed method was successfully applied to the accurate determination of six LPCs biomarkers of plasma in patients with psoriasis (n = 10) and control groups (n = 10).
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http://dx.doi.org/10.1016/j.jpba.2021.114101DOI Listing
July 2021

Immunogenicity of Varicella-Zoster Virus Glycoprotein E Formulated with Lipid Nanoparticles and Nucleic Immunostimulators in Mice.

Vaccines (Basel) 2021 Mar 25;9(4). Epub 2021 Mar 25.

Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China.

Theoretically, the subunit herpes zoster vaccine Shingrix could be used as a varicella vaccine that avoids the risk of developing shingles from vaccination, but bedside mixing strategies and the limited supply of the adjuvant component QS21 have made its application economically impracticable. With lipid nanoparticles (LNPs) that were approved by the FDA as vectors for severe acute respiratory syndrome coronavirus 2 vaccines, we designed a series of vaccines efficiently encapsulated with varicella-zoster virus glycoprotein E (VZV-gE) and nucleic acids including polyinosinic-polycytidylic acid (Poly I:C) and the natural phosphodiester CpG oligodeoxynucleotide (CpG ODN), which was approved by the FDA as an immunostimulator in a hepatitis B vaccine. Preclinical trial in mice showed that these LNP vaccines could induce VZV-gE IgG titers more than 16 times those induced by an alum adjuvant, and immunized serum could block in vitro infection completely at a dilution of 1:80, which indicated potential as a varicella vaccine. The magnitude of the cell-mediated immunity induced was generally more than 10 times that induced by the alum adjuvant, indicating potential as a zoster vaccine. These results showed that immunostimulatory nucleic acids together with LNPs have promise as safe and economical varicella and zoster vaccine candidates.
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http://dx.doi.org/10.3390/vaccines9040310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064366PMC
March 2021

Polymorphisms of microRNAs are associated with salt sensitivity in a Han Chinese population: the EpiSS study.

J Hum Hypertens 2021 Mar 31. Epub 2021 Mar 31.

Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University and Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China.

The majority of single-nucleotide polymorphism (SNP) association studies of salt sensitivity (SS) have focused on SNPs in protein-coding genes rather than on SNPs in noncoding RNAs. This study attempted to identify the association between whole blood microRNA (miRNA)-related SNPs and the risk of SS in a Han Chinese population. A case-control study of 762 individuals was performed. A modified Sullivan's acute oral saline load and diuresis shrinkage test was used to assess SS. All SNPs were analysed by RT-PCR on a Sequenom Mass ARRAY Platform (Sequenom, San Diego, CA, USA). A genetic risk score (GRS) was used to evaluate the joint genetic effect. In total, 24 miRNA-related SNPs were genotyped, four of which (miR-1307-5p/rs11191676, miR-1307-5p/rs2292807, miR-145/rs41291957 and miR-4638-3p/rs6601178) were associated with both SS and salt sensitivity of blood pressure (SSBP) (p ≤ 0.05). MiR-382-5p/rs4906032 and miR-15b-5/rs10936201 were associated with SSBP. Weighted GRS showed that participants in the second, third and fourth quartiles had 1.760-fold (95% CI: 1.068-2.903), 2.450-fold (95% CI: 1.470-4.083) and 2.774-fold (95% CI: 1.680-4.582) increased risk of SS, respectively. Bioinformatics analysis indicated that these four SNP risk alleles may affect transcription factor binding and influence promoter activity. A total of six miRNA-related SNPs were found to be associated with SS or SSBP, and the presence of multiple risk alleles resulted in increased risk level.
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http://dx.doi.org/10.1038/s41371-021-00485-9DOI Listing
March 2021

Conversion of esters to thioesters under mild conditions.

Org Biomol Chem 2021 04 18;19(13):2991-2996. Epub 2021 Mar 18.

Shandong Lunan Coal Chemical Research Institute of Engineering and Technology, Zaozhuang University, 1 Bei'an Road, Zaozhuang, Shandong 277160, China.

We report conversion of esters to thioesters via selective C-O bond cleavage/weak C-S bond formation under transition-metal-free conditions. The method is notable for a general and practical transition-metal-free system, broad substrate scope and excellent functional group tolerance. The strategy was successfully deployed in late-stage thioesterification, site-selective cross-coupling/thioesterification/decarbonylation and easy-to-handle gram scale thioesterification. Selectivity and computational studies were performed to gain insight into the formation of weak C-S bonds by C-O bond cleavage, which contrasts with the traditional trend of nucleophilic additions to carboxylic acid derivatives.
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http://dx.doi.org/10.1039/d1ob00187fDOI Listing
April 2021

Metabolic profiling reveals interleukin-17A monoclonal antibody treatment ameliorate lipids metabolism with the potentiality to reduce cardiovascular risk in psoriasis patients.

Lipids Health Dis 2021 Feb 18;20(1):16. Epub 2021 Feb 18.

School of Pharmacy, Fudan University, Shanghai, 201203, People's Republic of China.

Background: Psoriasis is a common chronic inflammatory skin disease associated with overproduction of interleukin-17A (IL-17A). IL-17A monoclonal antibodies (mAbs) have shown clinical efficacy in psoriasis patients. Although a series of different overlapping mechanisms have been found to establish a link between psoriasis and cardiovascular diseases, the underlying mechanisms of the two types of diseases and the potential efficacy of IL-17A mAbs in amelioration of cardiovascular comorbidities remain unclear.

Methods: Serum samples from two study cohorts including 117 individuals were analyzed using a high-throughput UHPLC-MS platform. Non-targeted metabolic profiling analysis was first conducted with samples from 28 healthy individuals and from 28 psoriasis patients before and after 12-weeks of ixekizumab treatment in study cohort 1. Study cohort 2 was additionally recruited to validate the correlations of the identified metabolites with cardiovascular diseases.

Results: A total of 43 differential metabolites, including lysophospholipids, free fatty acids, acylcarnitines and dicarboxylic acids, were accurately identified in study cohort 1, and the analysis showed that lipid metabolism was impaired in psoriasis patients. Compared with healthy individuals, psoriasis patients had higher levels of lysophosphatidylcholines, lysophosphatidylinositols, lysophosphatidic acids and free fatty acids, but lower levels of acylcarnitines and dicarboxylic acids. The identified dicarboxylic acid levels were inversely correlated with psoriasis area and severity index (PASI) scores (P < 0.05). The results for study cohort 2 were largely consistent with the results for study cohort 1. Moreover, the levels of all identified lysophosphatidylcholines were higher in psoriasis patients with coronary heart diseases than in psoriasis without coronary heart disease. Notably, most of these lipidic changes were ameliorated by ixekizumab treatment.

Conclusion: The results of this non-targeted metabolomic analysis indicate that treatment with IL-17A mAbs can not only ameliorate psoriasis lesions but also restore dysregulated lipid metabolism to normal levels in psoriasis patients. Considering that dysregulated lipid metabolism has been regarded as the critical factor in cardiovascular diseases, the recovery of lipid metabolites in psoriasis patients indicates that IL-17A mAbs might have the potential protective effects against cardiovascular comorbidities.
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http://dx.doi.org/10.1186/s12944-021-01441-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890626PMC
February 2021

Association of chronic diseases with depression, anxiety and stress in Chinese general population: The CHCN-BTH cohort study.

J Affect Disord 2021 03 14;282:1278-1287. Epub 2021 Jan 14.

Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University and Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, 100069, China.. Electronic address:

Background Large-scale epidemiological surveys focusing on characteristic differences in psychological and physical health conditions in Chinese adults are lacking. Objective To investigate the association of noncommunicable chronic diseases (NCDs) with depression, anxiety and stress in the Chinese general population. Methods A total of 13784 participants were recruited from the baseline survey of the Cohort Study on Chronic Disease of Communities Natural Population in Beijing, Tianjin and Hebei (CHCN-BTH) from 2017 to 2019. Sociodemographic characteristics, lifestyle and NCDs were assessed via questionnaire. Stress, anxiety and depression were assessed by the Depression-Anxiety-Stress Scale (DASS-21). The relationship of NCDs with psychological symptoms was determined through logistic regression analysis. Results Multivariate logistic regression analysis revealed that the prevalence of stress (OR = 1.640; 95% CI: 1.381-1.949), anxiety (OR = 1.654; 95% CI: 1.490-1.837) and depression (OR = 1.460; 95% CI: 1.286-1.658) symptoms were all significantly higher in patients with NCDs. Multimorbidities were associated with a higher risk of stress (OR = 2.310; 95% CI: 1.820-2.931), anxiety (OR = 2.119; 95% CI: 1.844-2.436) and depression (OR = 2.785; 95% CI: 1.499-2.126) than single NCDs. A course of disease within 1 year or more than 5 years also was associated with a higher risk. Limitations The cross-sectional design could not examine the causal link between psychological symptoms and NCDs. Conclusion Psychological symptoms were more prevalent among individuals with NCDs in the Chinese general population. This study suggests that more attention should be paid to the mental health problems of patients with NCDs.
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http://dx.doi.org/10.1016/j.jad.2021.01.040DOI Listing
March 2021

Efficient manipulation of gene dosage in human iPSCs using CRISPR/Cas9 nickases.

Commun Biol 2021 02 12;4(1):195. Epub 2021 Feb 12.

Division of Life Science, State Key Laboratory of Molecular Neuroscience, Center for Stem Cell Research, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.

The dysregulation of gene dosage due to duplication or haploinsufficiency is a major cause of autosomal dominant diseases such as Alzheimer's disease. However, there is currently no rapid and efficient method for manipulating gene dosage in a human model system such as human induced pluripotent stem cells (iPSCs). Here, we demonstrate a simple and precise method to simultaneously generate iPSC lines with different gene dosages using paired Cas9 nickases. We first generate a Cas9 nickase variant with broader protospacer-adjacent motif specificity to expand the targetability of double-nicking-mediated genome editing. As a proof-of-concept study, we examine the gene dosage effects on an Alzheimer's disease patient-derived iPSC line that carries three copies of APP (amyloid precursor protein). This method enables the rapid and simultaneous generation of iPSC lines with monoallelic, biallelic, or triallelic knockout of APP. The cortical neurons generated from isogenically corrected iPSCs exhibit gene dosage-dependent correction of disease-associated phenotypes of amyloid-beta secretion and Tau hyperphosphorylation. Thus, the rapid generation of iPSCs with different gene dosages using our method described herein can be a useful model system for investigating disease mechanisms and therapeutic development.
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http://dx.doi.org/10.1038/s42003-021-01722-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881037PMC
February 2021

Elevated lipoprotein(a) and risk of coronary heart disease according to different lipid profiles in the general Chinese community population: the CHCN-BTH study.

Ann Transl Med 2021 Jan;9(1):26

Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University and Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China.

Background: To evaluate the contributions of elevated lipoprotein(a) [Lp(a)] to the risk of coronary heart disease (CHD) in the general Chinese community population according to different lipid profiles.

Methods: We recruited individuals aged over 18 years from the baseline survey of the Cohort Study on Chronic Disease of Communities Natural Population in Beijing, Tianjin and Hebei (CHCN-BTH) using a stratified, multistage cluster sampling method. Data were collected through questionnaire surveys, anthropometric measures and laboratory tests. Restricted cubic spline (RCS) functions, multivariate logistic regression, sensitivity analyses and stratified analyses were used to evaluate the association between Lp(a) and CHD.

Results: A total of 25,343 participants were included, with 1,364 (5.38%) identified as having CHD. Elevated Lp(a) levels were linearly related to an increased risk of CHD (P<0.0001 and P=0.8468). Multivariate logistic regression analysis indicated that subjects with Lp(a) ≥300 mg/L had a higher risk of CHD [OR (95% CI): 1.36 (1.17, 1.57)] than did individuals with Lp(a) <300 mg/L. Compared with individuals with Lp(a) <119.0 mg/L (<50th percentile), the ORs (95% CI) for CHD in the 51st-80th, 81st-95th and >95th percentiles were 1.07 (0.93, 1.23), 1.26 (1.07, 1.50) and 1.68 (1.30, 2.17), respectively (P for trend <0.0001). This association was also found among the subgroup of subjects without dyslipidemia, including those with normal total cholesterol (TC) (<6.2 mmol/L), triglycerides (TG) (<2.3 mmol/L), high-density lipoprotein cholesterol (HDL-C) (≥1.0 mmol/L) and low-density lipoprotein cholesterol (LDL-C) (<4.1 mmol/L). Elevated Lp(a) and dyslipidemia significantly contributed to a higher risk of CHD with synergistic effects. Stratified analyses showed that elevated Lp(a) concentrations were significantly associated with an increased risk of CHD in the subgroups of individuals who were noncurrent drinkers, overweight individuals, individuals with hypertension, individuals who engaged in moderate physical activity, those without diabetes mellitus and individuals in Beijing and Tianjin.

Conclusions: Elevated Lp(a) concentrations were linearly associated with a higher risk of CHD in the general Chinese community population, especially in normolipidemic subjects. Both dyslipidemia and elevated Lp(a) independently or synergistically contributed to the risk of CHD. Our results suggest that more attention should be paid to the levels of Lp(a) in normolipidemic subjects, which may be an early predictor of CHD.
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http://dx.doi.org/10.21037/atm-20-3899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859748PMC
January 2021

A Dynamic Hysteresis Model and Nonlinear Control System for a Structure-Integrated Piezoelectric Sensor-Actuator.

Sensors (Basel) 2021 Jan 3;21(1). Epub 2021 Jan 3.

State Key Laboratory of Robotics and System, Harbin Institute of Technology, Harbin 150001, China.

The piezoelectric sensor-actuator plays an important role in micro high-precision dynamic systems such as medical robots and micro grippers. These mechanisms need high-precision position control, while the size of the sensor and actuator should be as small as possible. For this paper, we designed and manufactured a structure-integrated piezoelectric sensor-actuator and proposed its PID (Proportion Integral Differential) control system based on the dynamic hysteresis nonlinear model and the inverse model. Through simplifying the structure of the piezoelectric sensor-actuator by the centralized parameter method, this paper establishes its dynamic model and explores the input-output transfer function by taking the relationship between the output force and displacement as the medium. The experiment shows the maximum distance of the hysteresis curve is 0.26 μm. By parsing the hysteresis curve, this paper presents a dynamic hysteresis nonlinear model and its inverse model based on a 0.5 Hz quasi-static model and linear transfer function. Simulation results show that the accuracy of the static model is higher than that of the dynamic model when the frequency is 0.5 Hz, but the compensation accuracy of the dynamic model is obviously better than that of the static model with the increase of the frequency. This paper also proposes a control system for the sensor-actuator by means of the inverse model. The simulation results indicate that the output root mean square error was reduced to one-quarter of the original, which proves that the structure-integrated piezoelectric sensor-actuator and its control system have a great significance for signal sensing and output control of micro high-precision dynamic systems.
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http://dx.doi.org/10.3390/s21010269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794881PMC
January 2021

Discrepant acute effect of saline loading on blood pressure, urinary sodium and potassium according to salt intake level: EpiSS study.

J Clin Hypertens (Greenwich) 2021 02 21;23(2):289-300. Epub 2020 Nov 21.

Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China.

Acute dietary salt intake may cause an elevation in blood pressure (BP). The study aimed to assess the acute effect of saline loading on BP in subjects with different levels of salt intake. This study is based on the baseline survey of systemic epidemiology of salt sensitivity study. The sodium excretion in the 24-hour urine was calculated for estimating the level of salt intake. Subjects were performed an acute oral saline loading test (1 L), and data of 2019 participants were included for analyses. Multivariate linear regression and stratified analyses were performed to identify associations between 24-hour urinary sodium (24hUNa) with BP changes. Due to saline loading, systolic BP (SBP), pulse pressure, and urinary sodium concentration were significantly increased, while diastolic BP, heart rate, and urinary potassium concentration were significantly decreased. The SBP increments were more significant in subjects with lower salt intake, normotensives, elders, males, smokers, and drinkers. There was a significant linear negative dose-response association between SBP increment with 24hUNa (β = -0.901, 95% CI: -1.253, -0.548), especially in lower salt intake individuals (β = -1.297, 95% CI: -2.338, -0.205) and hypertensive patients (β = -1.502, 95% CI: -2.037, -0.967). After excluding patients who received antidiabetic or antihypertensive medicines, the effects of negative associations weakened but remained significantly. In conclusion, acute salt loading leads to an increment in SBP, and the increased SBP was negatively related with 24hUNa. This study indicated avoiding acute salt loading was important for escaping acute BP changes, especially in lower salt intake populations.
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http://dx.doi.org/10.1111/jch.14106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8029760PMC
February 2021

Identification of lncRNA-NR_104160 as a biomarker and construction of a lncRNA-related ceRNA network for essential hypertension.

Am J Transl Res 2020 15;12(10):6060-6075. Epub 2020 Oct 15.

Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing Municipal Key Laboratory of Clinical Epidemiology Beijing 100069, People's Republic of China.

Objectives: To identify long noncoding RNAs (lncRNAs) and construct a competing endogenous RNA (ceRNA) network for essential hypertension.

Methods: An RNA microarray and two-step quantitative real-time PCR were applied to identify differentially expressed RNAs (DE-RNAs), and a luciferase assay was performed to explore the binding relationship between RNAs. A generalized linear model and logistic regression model were used to analyze the associations between different RNAs and of RNAs with hypertension. Receiver operating characteristic curve analysis was executed to evaluate the diagnostic performance. Bioinformatics analysis was applied for network construction.

Results: In total, 439 DE-RNAs (387 lncRNAs and 52 mRNAs) were identified in the microarray, and 71 'lncRNA-miRNA-mRNA' loops formed the ceRNA network. The first validation confirmed that five RNAs (NR_104160, lnc-GPR63-8:1, lnc-HPRT1-9:1, and ) were significantly upregulated in hypertensives ( < 0.05). NR_104160 was significantly associated with hypertension (OR = 2.863, 95% CI: 1.143-7.172; = 0.025) after adjusting for confounding factors. NR_104160 was included in the hypertension diagnostic model, with an area under the curve of 0.852 (95% CI: 0.761-0.944). In the second validation, NR_104160 showed a constant significant difference ( = 0.001). An elevated expression level of NR_104160 was associated with the expression of ( = 0.2235, = 0.005). Luciferase assays showed hsa-miR-101-3p stimulation significantly inhibited the reporter gene activation ability of the NR_104160 wild-type plasmid ( < 0.001).

Conclusions: Our study constructed a ceRNA network to provide hypotheses regarding the mechanism of hypertension development. lncRNA-NR_104160 was identified as a hub element that participates in hypertension transcriptional regulation and as a potential biomarker.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653565PMC
October 2020
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