Publications by authors named "Liang Hong"

1,096 Publications

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High anticancer activity and apoptosis- and autophagy-inducing properties of novel lanthanide(III) complexes bearing 8-hydroxyquinoline--oxide and 1,10-phenanthroline.

Dalton Trans 2021 May;50(17):5828-5834

State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin 541004, PR China.

In the quest for rare earth metal complexes with enhanced cancer chemotherapeutic properties, the discovery of seven lanthanide(iii) complexes bearing 8-hydroxyquinoline-N-oxide (NQ) and 1,10-phenanthroline (phen) ligands, i.e., [SmIII(NQ)(phen)(H2O)Cl2] (Ln1), [EuII(NQ)(phen)(H2O)Cl2] (Ln2), [GdIII(NQ)(phen)(H2O)Cl2] (Ln3), [DyIII(NQ)(phen)(H2O)Cl2] (Ln4), [HoIII(NQ)(phen)(H2O)Cl2] (Ln5), [ErIII(NQ)(phen)(H2O)Cl2] (Ln6), and [YbIII(NQ)(phen)(H2O)Cl2] (Ln7), as potential anticancer drugs is described. Complexes Ln1-Ln7 exhibit high antiproliferative activity against cisplatin-resistant A549/DDP cells (IC50 = 0.025-0.097 μM) and low toxicity to normal HL-7702 cells. Moreover, complex Ln1, and to a lesser extent Ln7, can upregulate the expression of LC3 and Beclin1 and downregulate p62 to induce apoptosis in cisplatin-resistant A549/DDP cell lines, which is related to the cell autophagy-inducing properties of Ln1 and Ln7. Furthermore, in vivo assays suggest that Ln1 significantly inhibits A549/DDP xenograft tumor growth (56.5%). These results indicate that lanthanide(iii) complex Ln1 is a promising candidate as an anticancer drug against cisplatin-resistant A549/DDP cells.
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http://dx.doi.org/10.1039/d1dt00450fDOI Listing
May 2021

Heat Shock Protein 90 Inhibitor Effects on Pancreatic Cancer Cell Cultures.

Pancreas 2021 Apr;50(4):625-632

Departments of Pathology and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD.

Objectives: Pancreatic ductal adenocarcinoma is one of the deadliest cancers for which few curative therapies are available to date. Heat shock protein 90 (Hsp90) inhibitors have shown activity against numerous cancers in vitro; therefore, we tested whether they could be used to target pancreatic ductal adenocarcinoma.

Methods: Inhibitors of Hsp90 ATPase activity were applied on low-passage pancreatic cell line cultures (Panc10.05, Panc215, A6L) in a dose-response manner, and the inhibitor in vitro effect on cell growth was evaluated. Seven of novel Hsp90 inhibitors based on resorcinol fragment and 5 commercially available Hsp90 inhibitors (17-AAG, AT-13387, AUY-922, ganetespib, and rifabutin) as well as control compound triptolide were tested yielding IC50 values in 2- and 3-dimensional assays.

Results: The novel Hsp90 inhibitors exhibited strong effects on all 3 tested pancreatic cell line cultures (Panc10.05, Panc215, A6L) reaching the IC50 of 300 to 600 nM in 2- and 3-dimensional assays.

Conclusions: Novel Hsp90 inhibitors can be developed as antipancreatic cancer agents. Their chemical structures are simpler, and they are likely to exhibit lower side effects than the much more complex inhibitors used as controls.
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http://dx.doi.org/10.1097/MPA.0000000000001807DOI Listing
April 2021

Sesquiterpenoids from .

Nat Prod Res 2021 May 5;35(9):1537-1543. Epub 2019 Sep 5.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, China.

One new cis -coumaroyl copaborneol-type sesquiterpenoid (), together with its known trans isomer () and six other known -coumaroyl humulane-type sesquiterpenoids (), were isolated from the whole plants of . Their structures were determined by spectroscopic data. Compounds exhibited moderate antimycobacterial activity against HRv.
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http://dx.doi.org/10.1080/14786419.2019.1660330DOI Listing
May 2021

Genome-wide variant-based study of genetic effects with the largest neuroanatomic coverage.

BMC Bioinformatics 2021 Apr 30;22(1):223. Epub 2021 Apr 30.

Computer and Information Science, IUPUI, 723 W Michigan St, Indianapolis, IN, 46202, USA.

Background: Brain image genetics provides enormous opportunities for examining the effects of genetic variations on the brain. Many studies have shown that the structure, function, and abnormality (e.g., those related to Alzheimer's disease) of the brain are heritable. However, which genetic variations contribute to these phenotypic changes is not completely clear. Advances in neuroimaging and genetics have led us to obtain detailed brain anatomy and genome-wide information. These data offer us new opportunities to identify genetic variations such as single nucleotide polymorphisms (SNPs) that affect brain structure. In this paper, we perform a genome-wide variant-based study, and aim to identify top SNPs or SNP sets which have genetic effects with the largest neuroanotomic coverage at both voxel and region-of-interest (ROI) levels. Based on the voxelwise genome-wide association study (GWAS) results, we used the exhaustive search to find the top SNPs or SNP sets that have the largest voxel-based or ROI-based neuroanatomic coverage. For SNP sets with >2 SNPs, we proposed an efficient genetic algorithm to identify top SNP sets that can cover all ROIs or a specific ROI.

Results: We identified an ensemble of top SNPs, SNP-pairs and SNP-sets, whose effects have the largest neuroanatomic coverage. Experimental results on real imaging genetics data show that the proposed genetic algorithm is superior to the exhaustive search in terms of computational time for identifying top SNP-sets.

Conclusions: We proposed and applied an informatics strategy to identify top SNPs, SNP-pairs and SNP-sets that have genetic effects with the largest neuroanatomic coverage. The proposed genetic algorithm offers an efficient solution to accomplish the task, especially for identifying top SNP-sets.
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http://dx.doi.org/10.1186/s12859-021-04145-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086096PMC
April 2021

MADS-Box Protein Complex VvAG2, VvSEP3 and VvAGL11 Regulates the Formation of Ovules in L. cv. 'Xiangfei'.

Genes (Basel) 2021 Apr 26;12(5). Epub 2021 Apr 26.

College of Horticulture, China Agricultural University, Beijing 100193, China.

The phenomenon of multi-carpel and multi-ovule exists in the grapevine cultivar 'Xiangfei', but the mechanism of ovule formation is seldom reported. In this study, we observed the ovule formation process by using 'Xiangfei' grapes. The role of the () gene in ovule formation was identified, and we explored the relationship between VvAG2, VvSEP3(VvMADS4) and VvAGL11(VvMADS5) proteins. The results showed that the ovule primordium appeared when the inflorescence length of 'Xiangfei' grapes were 4-5 cm long; the relative expression levels of , and genes were higher during ovule formation, and the expression levels of gene was the highest. Transgenic tomato () plants expressing produced higher numbers of ovules and carpels than the wild type. Moreover, yeast two-hybrid and yeast three-hybrid experiments demonstrated that VvSEP3 acts as a bridge and interacts with VvAG2 and VvAGL11 proteins, respectively. Meanwhile, a homodimer can be formed between VvSEP3 and VvSEP3, but there was no interaction between VvAG2 and VvAGL11. These findings suggest that the gene is involved in the formation of ovules, and VvAG2/VvSEP3 together with VvAGL11/VvSEP3 can form a tetrameric complex. In summary, our data showed that along with and jointly regulate the ovule formation of 'Xiangfei' grapes.
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http://dx.doi.org/10.3390/genes12050647DOI Listing
April 2021

Development of a Vaccine against SARS-CoV-2 Based on the Receptor-Binding Domain Displayed on Virus-Like Particles.

Vaccines (Basel) 2021 Apr 16;9(4). Epub 2021 Apr 16.

International Immunology Centre, Anhui Agricultural University, Hefei 230036, China.

The ongoing coronavirus disease (COVID-19) pandemic is caused by a new coronavirus (severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)) first reported in Wuhan City, China. From there, it has been rapidly spreading to many cities inside and outside China. Nowadays, more than 110 million cases with deaths surpassing 2 million have been recorded worldwide, thus representing a major health and economic issues. Rapid development of a protective vaccine against COVID-19 is therefore of paramount importance. Here, we demonstrated that the recombinantly expressed receptor-binding domain (RBD) of the spike protein can be coupled to immunologically optimized virus-like particles derived from cucumber mosaic virus (CuMV). The RBD displayed CuMV bound to ACE2, the viral receptor, demonstrating proper folding of RBD. Furthermore, a highly repetitive display of the RBD on CuMV resulted in a vaccine candidate that induced high levels of specific antibodies in mice, which were able to block binding of the spike protein to ACE2 and potently neutralize SARS-CoV-2 virus in vitro.
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http://dx.doi.org/10.3390/vaccines9040395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073353PMC
April 2021

Prenatal exposure to residential PM and its chemical constituents and weight in preschool children: A longitudinal study from Shanghai, China.

Environ Int 2021 Apr 24;154:106580. Epub 2021 Apr 24.

NHC Key Lab. Of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), School of Public Health, Fudan University, 779 Old Hu Min Road, Shanghai 200237, China.

Background: Studies have reported that prenatal exposure to fine particulate matter (PM) might be associated with adverse birth outcomes in offspring. However, evidence with regard to the effects of prenatal exposure to PM and, especially, its main chemical constituents on offspring's weight in childhood is limited and inconsistent.

Objectives: The present study aimed to examine associations of prenatal exposure to PM total mass and its chemical constituents in each trimester with children's weight from birth to 6 years of age using data from Shanghai-Minhang Birth Cohort Study.

Methods: A total of 1,084 mother-infant pairs were included with both PM exposure data and at least one measurement of weight and height. Weight-for-Length (WLZ), BMI-for-Age (BMIz), and Weight-for-Age (WAZ) z-scores were generated according to the World Health Organization guidelines. Exposure to PM total mass and its chemical constituents [organic carbon (OC), black carbon (BC), ammonium (NH), nitrate (NO), sulfate (SO), and soil dust (SOIL)] during pregnancy was estimated from a satellite based modelling framework. We used multiple informant model to estimate the associations of trimester-specific PM total mass and its specific constituents concentrations with WLZ/BMIz and WAZ of offspring at birth and 1, 4, and 6 years of age.

Results: In multiple informant model, we observed consistent patterns of associations between exposure to PM total mass, OC, BC, NH, NO, and SO during the 2 and 3 trimesters and decreased WLZ/BMIz and WAZ at 1, 4, and 6 years of age in boys. We observed associations between prenatal exposure to PM total mass, NH, and NO during the 1 and 2 trimesters and increased WLZ/BMIz and WAZ in girls at birth. However, there were null associations at 1 and 4 years of age and inverse associations at 6 years of age.

Conclusions: Prenatal exposure to PM total mass and its main chemical constituents was associated with decreased weight in boys from 1 to 6 years of age, with increased weight at birth and decreased weight at 6 years of age in girls. Our findings suggest that prenatal exposure to PM and its chemical constituents may have a lasting effect on offspring's weight in childhood.
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http://dx.doi.org/10.1016/j.envint.2021.106580DOI Listing
April 2021

Predicting candidate therapeutic drugs for sepsis-induced acute respiratory distress syndrome based on transcriptome profiling.

Bioengineered 2021 Dec;12(1):1369-1380

Institute of Clinical Medicine Research, The Affiliated Suzhou Science and Technology Town Hospital of Nanjing Medical University, Suzhou, China.

Sepsis-induced acute respiratory distress syndrome (ARDS) remains a major threat to human health without effective therapeutic drugs. Previous studies demonstrated the power of gene expression profiling to reveal pathological changes associated with sepsis-induced ARDS. However, there is still a lack of systematic data mining framework for identifying potential targets for treatment. In this study, we demonstrated the feasibility of druggable targets prediction based on gene expression data. Through the functional enrichment analysis of microarray-based expression profiles between sepsis-induced ARDS and non-sepsis ARDS samples, we revealed genes involved in anti-microbial infection immunity were significantly altered in sepsis-induced ARDS. Protein-protein interaction (PPI) network analysis highlighted TOP2A gene as the key regulator in the dysregulated gene network of sepsis-induced ARDS. We were also able to predict several therapeutic drug candidates for sepsis-induced ARDS using Connectivity Map (Cmap) database, among which doxorubicin was identified to interact with TOP2A with a high affinity similar to its endogenous ligand. Overall, our findings suggest that doxorubicin could be a potential therapeutic for sepsis-induced ARDS by targeting TOP2A, which requires further investigation and validation. The whole study relies on publicly available dataset and publicly accessible database or bioinformatic tools for data mining. Therefore, our study benchmarks a workflow for druggable target prediction which can be widely applicable in the search of targets in other pathological conditions.
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http://dx.doi.org/10.1080/21655979.2021.1917981DOI Listing
December 2021

Which wound cuts deeper: loss of an only child or loss of a spouse? An examination of bereavement in older adults within a Chinese cultural context.

Aging Ment Health 2021 Apr 26:1-9. Epub 2021 Apr 26.

Rory Meyers College of Nursing, New York University, New York, NY, USA.

Objectives: This study aimed to examine whether the loss of spouse had similar impacts on psychological well-being as the loss of the only child, and whether the presence of one mitigated the absence of the other.

Methods: We used data from a 2013 survey conducted in Shanghai, China. The sample included 1,200 older adults aged 60+, and 200 adults aged 45+ who lost their only child. Psychological well-being consisted of three dimensions: depression, loneliness, and life satisfaction. We applied logistic regression models to assess the impact of loss of spouse or children on psychological well-being. We further tested whether the impact differed by gender and whether social support mediated the relationship.

Results: Participants who have at least one living child but lost their spouse had less psychological distress than those who have a living spouse but lost their only child. This effect appeared to be stronger in women than in men. Social support mediated the relationship between bereavement and loneliness among women.

Conclusion: The findings suggested the loss of the only child is a more devastating event than the loss of spouse in Chinese adults. The loss of the only child is a major chronic stressor that has cumulative negative effect on psychological well-being.
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http://dx.doi.org/10.1080/13607863.2021.1913473DOI Listing
April 2021

A spatial study on Keshan disease prevalence and selenoprotein P in the Heilongjiang Province, China.

Int J Occup Med Environ Health 2021 Apr 12. Epub 2021 Apr 12.

Heilongjiang Center for Disease Control and Prevention, Harbin, China (Institute for Endemic Disease Control and Prevention).

Objectives: Few spatial studies on Keshan disease (KD) prevalence and serum selenoprotein P (SELENOP) levels have been reported in the Heilongjiang Province, China. This study aimed to investigate the spatial relationships between KD prevalence, SELENOP levels, and the socio-economic status for the precise prevention and control of KD.

Material And Methods: The study was carried out in all the 66 KD endemic counties in the Heilongjiang Province using a non-probability sampling method of a key village survey based on county-wide case-searching. The participants completed a questionnaire and had their serum SELENOP levels measured using enzyme-linked immunosorbent assay. Thematic maps were created, and spatial regression analysis was performed by ordinary least squares using ArcGIS 9.0.

Results: Overall, 53 676 residents were surveyed based on case-searching, and blood samples were collected from 409 residents. In total, 50 chronic KD cases were identified with a total prevalence of 9.3/10 000 population. The prevalence in the Tangyuan County was the highest (250/10 000 population). The mean serum SELENOP level was 13.96 mg/l. The spatial regression analysis showed that KD prevalence positively correlated with SELENOP levels and negatively with disposable income among rural residents.

Conclusions: The Tangyuan County should be considered for the precise prevention and control of KD. Further research is necessary to verify the reliability of SELENOP for estimating body selenium levels, and to better understand the relationship between selenium intake and KD in the investigated area.
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http://dx.doi.org/10.13075/ijomeh.1896.01749DOI Listing
April 2021

Clinical and Demographic Factors, Treatment Patterns, and Overall Survival Associated With Rare Triple-Negative Breast Carcinomas in the US.

JAMA Netw Open 2021 Apr 1;4(4):e214123. Epub 2021 Apr 1.

Department of Hematology-Oncology, Maroone Cancer Center, Cleveland Clinic Florida, Weston, Florida.

Importance: Triple-negative breast cancers are known collectively to demonstrate a more aggressive clinical course and earlier recurrence than cancers of other histological subtypes. However, the literature on rare triple-negative breast cancers and the association of histological type with survival and risk of metastasis is sparse.

Objective: To present the clinical and demographic characteristics, treatment patterns, and overall survival (OS) for histologically rare (<10% of breast cancers) triple-negative breast cancer types: medullary carcinoma, adenoid cystic carcinoma, and metaplastic breast carcinoma.

Design, Setting, And Participants: This cohort study was performed in the US using data reported by the National Cancer Database between 2010 and 2016. Confirmed cases of medullary carcinoma, adenoid cystic carcinoma, and metaplastic breast cancer were analyzed. Univariable analyses and multivariable Cox regression models were performed. Data analysis was performed from April to May 2020.

Main Outcomes And Measures: The primary outcome was 5-year OS. Secondary outcomes included site of metastasis, effect of immunohistochemistry, management, and 2-year mortality.

Results: A total of 8479 patients with breast cancer (mean [SD] age; 62.6 [14.3] years; 8435 women [99.48%]) were analyzed. Metaplastic carcinoma was the most commonly diagnosed histological type in this cohort, with 6867 patients (81%), followed by 1357 (16%) with adenoid cystic carcinoma and only 255 (3%) with medullary carcinoma. Medullary carcinoma presented earlier in life, at a median (interquartile range) age of 53 (45-62) years, compared with 62 (53-72) years for patients with adenoid cystic carcinoma and 63 (52-74) years for patients with metaplastic carcinoma. The proportion of tumors with triple-negative immunohistochemistry varied by histological type for medullary carcinoma (57 patients [22.4%]), adenoid cystic carcinoma (653 patients [48.1%]), and metaplastic carcinoma (3637 patients [53.0%]). Patients with adenoid cystic carcinoma were less likely to receive radiotherapy (711 patients [52.4%]) and chemotherapy (175 patients [12.9%]) compared with patients with medullary carcinoma (radiotherapy, 156 patients [61.2%]; chemotherapy, 190 patients [74.5%]) and metaplastic carcinoma (radiotherapy, 3416 patients [49.7%]; chemotherapy, 4709 patients [68.6%]). The 5-year OS rate was superior for patients with medullary (91.7%) and adenoid cystic carcinoma (88.4%) compared with patients with metaplastic carcinoma (63.1%). The 5-year mortality rate for adenoid cystic carcinoma was 8.33% vs 36.91% for metaplastic carcinoma.

Conclusions And Relevance: Nationally, over the course of 7 years, medullary carcinoma was most common and metaplastic carcinoma had the worst 5-year OS among the rare histological breast cancer subtypes analyzed. Factors associated with a poor prognosis for metaplastic carcinoma included advanced stage, lung metastasis, older age, and not receiving chemotherapy or radiation therapy. Future research focusing on rare subtypes of breast cancer is desirable and could inform the optimal management of these relatively understudied carcinomas.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.4123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042532PMC
April 2021

Stiffness of aortic arch and carotid arteries increases in -knockout mice with high-fat diet: evidence from echocardiography.

Am J Transl Res 2021 15;13(3):1352-1364. Epub 2021 Mar 15.

Department of Medicine, University of Illinois at Chicago Chicago, IL 60612, USA.

Arterial stiffness is an effective predictor of atherosclerosis. Measurement of pulse-wave velocity (PWV) is a gold-standard approach to study arterial stiffness. This study aims to examine arterial stiffness and heart functions via echocardiography at an early stage of atherosclerosis. A model of atherosclerosis in -knockout ( ) mice fed on high-fat diet (HFD) was used, with normal chow diet (ND) as a control. Stiffness of aortic arch and carotid arteries and left ventricular (LV) systolic/diastolic functions were measured by echocardiography. The plasma cholesterol levels and atherosclerotic plaque areas in the aortas were measured. The PWV values of aortic arch and carotid arteries were compared at 2, 4, 6 and 8 weeks with different diets. Compared with ND mice, PWV values in aortic arch and carotid arteries were significantly increased in HFD mice after 8 weeks (Aortic arch: 516.65 ± 216.89 cm/s vs. 192.53 ± 71.71 cm/s; Carotid arteries: 514.26 ± 211.01 cm/s vs. 188.03 ± 75.14 cm/s, respectively; both < 0.01) accompanied by the decrease in LV systolic/diastolic functions. These were well correlated with the increase in plasma cholesterol levels. Echo-based PWV measurement in the aortic arch was found more sensitive to predict atherosclerosis than in the carotid arteries in mice. Measuring aortic arch PWV via echocardiography could represent a new diagnostic strategy for early detection of atherosclerosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014403PMC
March 2021

Insights into two stable mainstream deammonification process and different microbial community dynamics at ambient temperature.

Bioresour Technol 2021 Jul 27;331:125058. Epub 2021 Mar 27.

State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150090, China; Center for Urban Environmental Remediation, Beijing University of Civil Engineering and Architecture, Beijing 100044, China. Electronic address:

How to achieve stable mainstream deammonification is still a huge challenge. In this work, satisfactory nitrogen removal were achieved in a deammonification granular sludge reactor (R1, 0.42 ± 0.03 kg N / (m·d)) and a mixed flocculent with granular sludge reactor (R2, 0.39 ± 0.04 kg N / (m·d)) at ambient temperature (21-28 ℃) . The good adaptability of anammox bacteria (Candidatus Jettenia) to ambient temperature ensured its efficient activity (0.84-1.54 mg N/(g VSS·h)). The overexpression ammonia monooxygenase gene abundances in ammonia oxidizing bacteria (Nitrosomonas) was also predicted. The inhibition of hydrazine and the competition of denitrifying bacteria (Denitratisoma) to nitrite nitrogen, leading to a low Nitrospira relative abundances (0.2%-2.1%) . It was also found that R1 was more resistant to the unfavorable condition. For R2, higher Denitratisoma abundances (9.2%-18.5%) and predicted metabolic pathway abundances related to carbon metabolism were observed.
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http://dx.doi.org/10.1016/j.biortech.2021.125058DOI Listing
July 2021

Hydrophilic Cross-Linked Aliphatic Hydrocarbon Diblock Copolymer as Proton Exchange Membrane for Fuel Cells.

Materials (Basel) 2021 Mar 26;14(7). Epub 2021 Mar 26.

Department of Chemical and Biomolecular Engineering, National University of Singapore, 10 Kent Ridge Crescent, Singapore 117585, Singapore.

This study proposes a hydrophobic and hydrophilic aliphatic diblock copolymer wherein the hydrophobic block contains glycidyl methacrylate (GMA) units that are distanced by poly(acrylonitrile) (PAN) segments to fabricate a proton exchange membrane (PEM). This diblock copolymer also known as ionomer due to the hydrophilic block comprising 3-sulfopropyl methacrylate potassium salt (SPM) block. The diblock copolymer was synthesized in the one-pot atom transfer radical polymerization (ATRP) synthesis. Subsequently, the membrane was fabricated by means of solution casting in which an organic diamine, e.g., ethylene diamine (EDA), was introduced to crosslink the diblock copolymer chains via the addition of amine to the epoxide group of GMA. As a result, the PEM attained possesses dual continuous phases, in which the hydrophobic domains are either agglomerated or bridged by the EDA-derived crosslinks, whereas the hydrophilic domains constitute the primary proton conducting channels. The in-situ crosslinking hydrophobic block by using a hydrophilic cross-linker represents the merit aspect since it leads to both improved proton conductivity and dimensional stability in alcohol fuel. To characterize the above properties, Nafion 117 and random copolymer of P(AN--GMA--SPM) were used as control samples. The PEM with the optimized composition demonstrates slightly better fuel cell performance than Nafion 117. Lastly, this diblock ionomer is nonfluorinated and hence favors lowering down both material and environmental costs.
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http://dx.doi.org/10.3390/ma14071617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036890PMC
March 2021

4-CPA (4-Chlorophenoxyacetic Acid) Induces the Formation and Development of Defective "Fenghou" () Grape Seeds.

Biomolecules 2021 Mar 30;11(4). Epub 2021 Mar 30.

College of Horticulture, China Agricultural University, Beijing 100193, China.

For some horticultural plants, auxins can not only induce normal fruit setting but also form fake seeds in the induced fruits. This phenomenon is relatively rare, and, so far, the underlying mechanism remains unclear. In this study, "Fenghou" ( × ) grapes were artificially emasculated before flowering and then sprayed with 4-CPA (4-chlorophenoxyacetic acid) to analyze its effect on seed formation. The results show that 4-CPA can induce normal fruit setting in "Fenghou" grapes. Although more seeds were detected in the fruits of the 4-CPA-treated grapevine, most seeds were immature. There was no significant difference in the seed shape; namely, both fruit seeds of the grapevines with and without 4-CPA treatment contained a hard seed coat. However, the immature seeds lacked embryo and endosperm tissue and could not germinate successfully; these were considered defective seeds. Tissue structure observation of defective seeds revealed that a lot of tissue redifferentiation occurred at the top of the ovule, which increased the number of cell layers of the outer integument; some even differentiated into new ovule primordia. The qRT-PCR results demonstrated that 4-CPA application regulated the expression of the genes and , which are associated with integument development in "Fenghou" grape ovules. Together, this study evokes the regulatory role of 4-CPA in the division and continuous redifferentiation of integument cells, which eventually develop into defective seeds with thick seed coats in grapes.
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http://dx.doi.org/10.3390/biom11040515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067128PMC
March 2021

Oleanane-type saponins and prosapogenins from Albizia julibrissin and their cytotoxic activities.

Phytochemistry 2021 May 23;185:112674. Epub 2021 Mar 23.

State Key Laboratory of Natural and Biomimetic Drugs and Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, 100191, China. Electronic address:

Two undescribed oleanane-type saponins, julibrosides K-L, along with three undescribed oleanane-type prosapogenins, julibrosides M-O, were isolated from the stem bark of Albizia julibrissin Durazz. and the mild alkaline hydrolysate of the total saponin, respectively. Their structures were established by extensive analysis of 1D and 2D NMR experiments (COSY, TOCSY, HSQC, HMBC, and HSQC-TOCSY) and mass spectrometry. Furthermore, the cytotoxic activities of the isolated compounds against BGC-823, A549, HCT-116, and HepG2 cell lines were evaluated, and julibroside L showed significant cytotoxic activities against the four cancer cell lines with IC values of 5.77, 4.80, 4.26, and 4.93 μM, respectively.
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http://dx.doi.org/10.1016/j.phytochem.2021.112674DOI Listing
May 2021

Classification of red blood cell aggregation using empirical wavelet transform analysis of ultrasonic radiofrequency echo signals.

Ultrasonics 2021 Jul 6;114:106419. Epub 2021 Mar 6.

Department of Electronic Engineering, Information School, Yunnan University, Kunming, Yunnan 650091, China.

Grading red blood cell (RBC) aggregation is important for the early diagnosis and prevention of related diseases such as ischemic cardio-cerebrovascular disease, type II diabetes, deep vein thrombosis, and sickle cell disease. In this study, a machine learning technique based on an adaptive analysis of ultrasonic radiofrequency (RF) echo signals in blood is proposed, and its feasibility for classifying RBC aggregation is explored. Using an adaptive empirical wavelet transform (EWT) analysis, the ultrasonic RF signals are decomposed into a series of empirical mode functions (EMFs); then, dominant empirical mode functions (DEMFs) are selected from the series. Six statistical characteristics, including the mean, variance, median, kurtosis, root mean square (RMS), and skewness are calculated for the locally normalized DEMFs, aiming to form primary feature vectors. Random forest (RDF) and support vector machine (SVM) classifiers are trained with the given feature vectors to obtain prediction models for RBC classification. Ultrasonic RF echo signals are acquired from five groups of six types of porcine blood samples with average numbers of aggregated RBCs of 1.04, 1.20, 1.83, 2.31, 2.72, and 4.28, respectively, to test the classification performance of the proposed method. The best subset with regard to the variance, kurtosis, and RMS is determined according to the maximum accuracy based on the RDF and SVM classifiers. The classification accuracies are 84.03 ± 3.13% for the RDF classifier, and 85.88 ± 2.99% for the SVM classifier. The mean classification accuracy of the SVM classifier is 1.85% better than that of the RDF classifier. In conclusion, the machine learning method is useful for the discrimination of varying degrees of RBC aggregation, and has potential for use in characterizing and monitoring the RBC aggregation in vessels.
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http://dx.doi.org/10.1016/j.ultras.2021.106419DOI Listing
July 2021

XRCC5/6 polymorphisms and their interactions with smoking, alcohol consumption, and sleep satisfaction in breast cancer risk: A Chinese multi-center study.

Cancer Med 2021 Apr 18;10(8):2752-2762. Epub 2021 Mar 18.

Department of Breast Surgery, Yantai Yuhuangding Hospital, Yantai, China.

Background: X-ray repair cross-complementary 5 (XRCC5) and 6 (XRCC6) are critical for DNA repair. Few studies have assessed their association with breast cancer risk, and related gene-environment interactions remain poorly understood. This study aimed to determine the influence of XRCC5/6 polymorphisms on breast cancer risk, and their interactions with cigarette smoking, alcohol consumption, and sleep satisfaction.

Methods: The study included 1039 patients with breast cancer and 1040 controls. Four single-nucleotide polymorphisms of XRCC5 and two of XRCC6 were genotyped. Information about smoking, alcohol consumption, and sleep satisfaction was collected through questionnaires. Odds ratios (OR) and related 95% confidence intervals (95% CI) were assessed using unconditional logistic regression models. Gene-environment interactions were analyzed using logistic regression with multiplicative interaction models.

Results: XRCC5 rs16855458 was associated with increased breast cancer risk in the co-dominant (p  = 0.003) and dominant (CA + AA vs. CC, OR = 1.29, 95% CI = 1.07-1.56, p = 0.008) genetic models after Bonferroni correction. The CG + GG genotype of XRCC6 rs2267437 was associated with an increased risk of estrogen receptor-negative/progesterone receptor-negative (ER-/PR-) breast cancer (CG + GG vs. CC: OR = 1.54, 95% CI = 1.12-2.13, p = 0.008) after Bonferroni correction. Moreover, an antagonistic interaction between XRCC5 rs16855458 and alcohol consumption (p  = 0.017), and a synergistic interaction between XRCC6 rs2267437 and sleep satisfaction were associated with breast cancer risk (p  = 0.0497). However, these interactions became insignificant after Bonferroni correction.

Conclusion: XRCC5 rs16855458 was associated with breast cancer risk, and XRCC6 rs2267437 was associated with the risk of ER-/PR- breast cancer. Breast cancer risk associated with XRCC5 and XRCC6 polymorphisms might vary according to alcohol consumption and sleep satisfaction, respectively, and merit further investigation.
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http://dx.doi.org/10.1002/cam4.3847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026916PMC
April 2021

The first copper(I) complex of anthrahydrazone with potential ROS scavenging activity showed significant in vitro anticancer activity by inducing apoptosis and autophagy.

J Inorg Biochem 2021 May 14;218:111390. Epub 2021 Feb 14.

School of Chemistry & Pharmaceutical Sciences, State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin 541004, PR China. Electronic address:

Based on the anticancer pharmacophore of anthrahydrazone and quinoline, a new quinolylanthrahydrazone ligand, 9-AQH (anthracene-9-quinolylhydrazone), was synthesized to further afford four metal complexes, [Co(9-AQH)(NO)(HO)] (1), [Ni(9-AQH)(HO)]·2NO (2), [Cu(9-AQH)]·NO (3), [Zn(9-AQH)(NO)]·NO (4), determined by X-ray single crystal diffraction analysis. The reaction of Cu(NO) with 9-AQH formed the stable and repeatable copper(I) complex 3. In vitro screening demonstrated only 3 showed significant and broad-spectrum anticancer activity, indicating that Cu(I) played a key role in exerting the anticancer activity. In solution, Cu(I) was not naturally oxidized to Cu(II) suggested by H-NMR (Nuclear Magnetic Resonance) and EPR (Electron Paramagnetic Resonance) analysis. The presence of 3 could also catalyze the HO system to give hydroxyl free radicals, suggested by further EPR and electrophoresis assay. At the cellular level, although no obvious Cu(II) signals were detected and the total ROS (Reactive Oxygen Species) scavenging in the tumor cells treated with 3, the potential redox property between Cu(I)/Cu(II), as a key role, should not be denied for the significant anticancer activity of 3, considering the much complicated circumstance and other reductive substances in cells. The anticancer mechanism of 3 on the most sensitive MGC-803 cells pointed to significant cell apoptosis through mitochondrial pathway, rather than cell cycle arrest. While the autophagy observed in tumor cells treated by 3 suggested its complicated anticancer mechanism, and whether there was an intrinsic correlation still needed to be further investigated.
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http://dx.doi.org/10.1016/j.jinorgbio.2021.111390DOI Listing
May 2021

Prenatal exposure to bisphenol analogues and digit ratio in children at ages 4 and 6 years: A birth cohort study.

Environ Pollut 2021 Jun 25;278:116820. Epub 2021 Feb 25.

NHC Key Lab. of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Public Health School, Fudan University, 779 Old Humin Road, Shanghai, China. Electronic address:

Bisphenol analogues (BPs), including bisphenol A (BPA), have been shown to exhibit similar endocrine disrupting activities. However, epidemiological evidence on the reproductive and developmental toxicities of BPs other than BPA is scarce. The second to fourth digit ratio (2D:4D), an endocrine-sensitive endpoint, has been suggested to be a biomarker of prenatal sex steroid exposure and associated with reproductive outcomes in later life. Using the data of 545 mother-child pairs from the Shanghai-Minhang Birth Cohort Study, we prospectively assessed the effects of prenatal exposure to BPs on 2D:4D in children at ages 4 and 6 years. Single-spot urine samples were collected in the third trimester and analyzed for BPs. Digit lengths were measured using a vernier caliper in children at ages 4 and 6 years, and the 2D:4D values for both hands were calculated. A multivariable linear regression model was applied to examine associations between prenatal BPs exposure and 2D:4D digit ratios at each age separately. The generalized estimating equation (GEE) model was used to deal with repeated 2D:4D measures obtained at ages 4 and 6 years. We found that prenatal exposure to BPA alternatives including BPF, BPS, and BPAF was associated with higher digit ratio in boys and/or girls (feminizing), while TCBPA, a halogenated bisphenol, was associated with lower 2D:4D in boys (masculinizing). These associations were more pronounced at 4 years of age, and tended to remain after further considering the potential confounding from prenatal co-exposure to other BPs and childhood BPs exposure. Our study provides epidemiological evidence that BPs exposure during pregnancy may alter the digit development in children, indicative of disrupted reproductive development in later life. Given these new findings, further studies are needed to corroborate our results.
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http://dx.doi.org/10.1016/j.envpol.2021.116820DOI Listing
June 2021

The significant interaction between age and diabetes mellitus for colorectal cancer: Evidence from NHANES data 1999-2016.

Prim Care Diabetes 2021 Mar 2. Epub 2021 Mar 2.

Department of Colorectal Surgery, Cleveland Clinic Florida, Weston, FL, USA. Electronic address:

Background: Diabetes mellitus has been associated with elevated risk of colorectal cancer (CRC), although interaction between age and DM is unclear. We examined the relationship among DM, CRC and age.

Methods: 22,580 subjects aged ≥18 years were identified from the National Health and Nutrition Examination Survey (NHANES) database collected between 1999-2016. To account for the complex, stratified, multistage probability sampling design in NHANES, SASv9.4 Procedure Survey Methodology was applied. Univariate analysis compared individual baseline characteristics between subjects with and without DM. Multivariate logistic regression model assessed association between DM and CRC, in which the model included factors with p<0.05 in univariate analysis as covariates.

Results: Univariate analysis showed significant differences in age (p<0.0001), race (p<0.0001), smoking (p=0.0023) and body mass index (p<0.0001) between No-DM and DM. Multivariate analysis revealed significant interaction between age and DM (p=0.0004). Subjects with DM aged 18-65 were more likely to experience CRC (OR=4.47, 95%CI=(1.33-15.07); p=0.0157) compared to those without DM. Subjects with DM aged >65 were not at increased risk for CRC (OR=0.83, 95%CI=(0.43-1.59); p=0.5665) compared to those without DM.

Conclusions: Age, DM, and interaction between age and DM are risk factors for CRC. Individuals with DM aged 18-65 years have a higher CRC risk.
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http://dx.doi.org/10.1016/j.pcd.2021.02.006DOI Listing
March 2021

Prognostic dynamic nomogram integrated with metabolic acidosis for in-hospital mortality and organ malperfusion in acute type B aortic dissection patients undergoing thoracic endovascular aortic repair.

BMC Cardiovasc Disord 2021 Mar 2;21(1):120. Epub 2021 Mar 2.

Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.

Background: Organ malperfusion is a lethal complication in acute type B aortic dissection (ATBAD). The aim of present study is to develop a nomogram integrated with metabolic acidosis to predict in-hospital mortality and organ malperfusion in patients with ATBAD undergoing thoracic endovascular aortic repair (TEVAR).

Methods: The nomogram was derived from a retrospectively study of 286 ATBAD patients who underwent TEVAR from 2010 to 2017 at a single medical center. Model performance was evaluated from discrimination and calibration capacities, as well as clinical effectiveness. The results were validated using a prospective study on 77 patients from 2018 to 2019 at the same center.

Results: In the multivariate analysis of the derivation cohort, the independent predictors of in-hospital mortality and organ malperfusion identified were base excess, maximum aortic diameter ≥ 5.5 cm, renal dysfunction, D-dimer level ≥ 5.44 μg/mL and albumin amount ≤ 30 g/L. The penalized model was internally validated by bootstrapping and showed excellent discriminatory (bias-corrected c-statistic, 0.85) and calibration capacities (Hosmer-Lemeshow P value, 0.471; Brier Score, 0.072; Calibration intercept, - 0.02; Slope, 0.98). After being applied to the external validation cohort, the model yielded a c-statistic of 0.86 and Brier Score of 0.097. The model had high negative predictive values (0.93-0.94) and moderate positive predictive values (0.60-0.71) for in-hospital mortality and organ malperfusion in both cohorts.

Conclusions: A predictive nomogram combined with base excess has been established that can be used to identify high risk ATBAD patients of developing in-hospital mortality or organ malperfusion when undergoing TEVAR.
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http://dx.doi.org/10.1186/s12872-021-01932-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927380PMC
March 2021

A spatial study on serum selenoprotein P and Keshan disease in Heilongjiang Province, China.

J Trace Elem Med Biol 2021 May 14;65:126728. Epub 2021 Feb 14.

Institute of Keshan Disease, Chinese Center for Endemic Disease Control, Harbin Medical University, Harbin, PR China. Electronic address:

Background: Few spatial studies on serum selenoprotein P (SELENOP) and Keshan disease (KD) have been reported at the county-level in Heilongjiang province, China. This study aimed to provide visualized spatial epidemiological evidence of selenium molecular marker in residents living in endemic areas for the precise assessment of prevention, control, and elimination of KD.

Methods: Using a spatial ecological study design, 587 subjects living in cities, townships, and rural areas of 50 KD endemic counties and 37 non-endemic counties in Heilongjiang province were investigated. The serum SELENOP levels of the participants were measured by enzyme-linked immunosorbent assay. Thematic maps were created, and spatial regression analysis was conducted using ordinary least squares.

Results: The mean serum SELENOP level of the 587 subjects was 7.4 ± 3.0 μg/mL. The mean levels of serum SELENOP were higher in cities (7.4 ± 2.9 μg/mL) and townships (7.9 ± 3.2 μg/mL) than in rural areas (6.0 ± 3.0 μg/mL). The mean levels of serum SELENOP were trending towards high levels in non-endemic areas (7.4 ± 3.0 μg/mL) than in KD endemic areas (6.3 ± 3.3 μg/mL). Spatial regression analysis showed that the serum SELENOP level was positively correlated with the per capita gross domestic product.

Conclusion: Selenium deficiency may still exist in some KD endemic counties in Heilongjiang province, including Lingdong, Nenjiang, and Baiquan; these counties should be considered as key areas for precision prevention, control, and elimination of KD. Inclusion of selenium in the national surveillance of KD will provide more evidence for the assessment of KD elimination from a selenium nutrition perspective.
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http://dx.doi.org/10.1016/j.jtemb.2021.126728DOI Listing
May 2021

Strategy to Chemically Decorate Nanopores of a Carbon Membrane for Filtrating Polyphenolics from Ethanol.

ACS Appl Mater Interfaces 2021 Mar 19;13(8):10524-10536. Epub 2021 Feb 19.

Department of Chemical & Biomolecular Engineering, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260, Singapore.

This study invents a post-pyrolysis modification approach to render the resulting carbon membrane (CM) competent for organic solvent nanofiltration (OSN). A bitumen coating on a porous stainless-steel disk (PSD) serves as the precursor for the intended carbon membrane (CM), which is attained through pyrolysis in Ar. The bitumen coating casts dual-pore networks in the CM because of the dominant asphaltene constituent in bitumen. The subsequent chemical decoration of CM was pursued through the following protocol: dopamine (DA) was deployed in the nanopores of CM via pressurized infiltration and followed by Tris buffer passes through to trigger in situ conversion of DA to polydopamine (PDA), which was affixed over the pore walls to furnish chemical affinity (termed as CM). Additionally, the catechol moiety of PDA was arranged to chelate with the Zn ion, aiming to trim the -OH anchor (termed as CM) to probe the effect of chelate on separation. The three membranes (CM, CM, and CM) were thereafter assessed by the separation of ethanol or isopropanol from phenolics [tannic acid (TA)/tetracycline (TC)]. A significantly improved OSN performance [rejection (%) ↔ permeance (L/(m·h·bar))] of CM vs CM was observed: (i) for TA feed, 13% ↔ 85 L/(m·h·bar) vs 83% ↔ 12 L/(m·h·bar); and (ii) for TC feed, 20% ↔ 78 L/(m·h·bar) vs 78% ↔ 12 L/(m·h·bar). Compared to CM, CM further advances the rejection performance (∼89% for TA and ∼80% for TC) over 50 h separation. They are benchmarked by the latest literature results. The performance enhancements can be attributed to the spreading of PDA or PDA-Zn sites in the dual-pore networks, so that they are able to offer H-bonding and steric blocking roles, a chemicomechanical effect, to seize solute molecules over pore walls. It is this interfacial drag effect that sustains the solute rejection.
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http://dx.doi.org/10.1021/acsami.0c17977DOI Listing
March 2021

A full-spectrum responsive B-TiO@SiO-HA nanotheranostic system for NIR-II photoacoustic imaging-guided cancer phototherapy.

J Mater Chem B 2021 03;9(8):2042-2053

State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, College of Chemistry and Pharmaceutical Science, Guangxi Normal University, Guilin, 541004, P. R. China.

The second near-infrared (NIR-II) window (1000-1350 nm) usually offers further improved light penetration, a higher maximum permissible exposure (MPE), and a lower background signal. Development of NIR-II optical diagnosis and phototherapy technologies is of great significance for precise, efficient tumor therapy. In this work, a new type of Ti-based targeting agent (B-TiO2@SiO2-HA) nanotheranostic system with strong NIR-II absorption was designed and fabricated for the first time. Oxygen vacancies were formed in B-TiO2 and its band gap was narrowed, resulting in nanotheranostic systems with full-spectrum responses to stimulation with light. The experimental results showed that B-TiO2@SiO2-HA not only can enable high NIR-II photothermal conversion and provide excellent reactive oxygen species (ROS) production capacity, but also can enable high-resolution photoacoustic imaging (PAI) under NIR-II laser irradiation. Moreover, HA modification gives the nanotheranostic systems the useful ability to target high-CD44-expression tumor cells and tissues. In vitro and in vivo experiments demonstrated that B-TiO2@SiO2-HA exhibited a targeted photothermal/photodynamic (PTT/PDT) effect that produced tumor-cell ablation and apoptosis under the guidance of real-time NIR-II PA imaging. B-TiO2@SiO2-HA exhibits precise nanotheranostic potential for PAI-guided tumor-targeting phototherapy.
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http://dx.doi.org/10.1039/d0tb02952aDOI Listing
March 2021

Association between prenatal exposure to polybrominated diphenyl ethers and anogenital distance in girls at ages 0-4 years.

Int J Hyg Environ Health 2021 Apr 11;233:113706. Epub 2021 Feb 11.

NHC Key Lab. of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai, China. Electronic address:

Anogenital distance (AGD) is a sensitive marker for the effect of in utero hormonal disturbance. However, studies on the associations between prenatal exposure to polybrominated diphenyl ethers (PBDEs), a group of endocrine disruptors, and AGD are limited. We examined the associations between prenatal PBDE exposure and AGD in girls at ages 0-4 years in the Shanghai-Minhang Birth Cohort Study. We measured PBDE in cord plasma collected from 148 girls at birth. Of them, two AGD metrics (AGD: from the anterior surface of the clitoral hood to the center of the anus; AGD: from the posterior end of the fourchette to the center of the anus) were measured in 142, 114, 104 and 120 of girls at birth, 6, 12, and 48 months of age, respectively. Linear regression models and linear mixed models were used to evaluate the associations between PBDE exposure and AGD at ages 0-4 years. We found positive associations of PBDE exposure with AGD and AGD in linear regression models, although some associations only reached significance at 6 and 48 months of age. For AGD, the associations were statistically significant for BDE-47, -99, and -100 at 6 months of age (β = 2.34, 95% CI (0.21, 4.48) for BDE-47; β = 2.21, 95% CI (0.05, 4.36) for BDE-99; β = 2.12, 95% CI (0.01, 4.23) for BDE-100), and for BDE-99 and -100 at 48 months of age (β = 4.49, 95% CI (1.27, 7.71) for BDE-99; β = 5.04, 95% CI (1.87, 8.22) for BDE-100), while statistically significant associations with AGD were only observed for BDE-99, -100, -153, and ∑PBDEs at 48 months of age (β = 7.62, 95% CI (2.59, 12.64) for BDE-99; β = 7.04, 95% CI (2.01, 12.07) for BDE-100; β = 5.41, 95% CI (0.45, 10.38) for BDE-153; β = 5.05 mm, 95% CI (0.09, 10.01 for ∑PBDEs). A consistent pattern of positive associations between prenatal exposure to PBDEs and AGD was also observed in linear mixed models. The finding provided further insights into the adverse effects of PBDEs on reproductive development at low dose exposure.
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http://dx.doi.org/10.1016/j.ijheh.2021.113706DOI Listing
April 2021

Risk of intellectual disability and maternal history of spontaneous abortion: a nationwide cohort study.

Dev Med Child Neurol 2021 Feb 13. Epub 2021 Feb 13.

Department of Clinical Medicine - Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark.

Aim: To investigate the association between a maternal history of spontaneous abortion and intellectual disability in children.

Method: This cohort study included 1 778 786 children (913 340 males, 865 085 females, 361 missing data; mean age 15y 2mo, SD 8y 11mo, range birth to 40y) born in Denmark between 1977 and 2016. Cox proportional hazard regression was used to estimate the hazard ratios (HRs) of intellectual disability.

Results: The overall HR of intellectual disability for children with a maternal history of spontaneous abortion was 1.17 (95% confidence interval [CI] 1.12-1.22) and the risk for multiple spontaneous abortions (HR=1.30, 95% CI 1.20-1.40) was higher than for a single spontaneous abortion (HR=1.13, 95% CI 1.07-1.18). When only cases of inpatient intellectual disability were included, the estimates increased slightly: the overall HR was 1.22 (95% CI 1.12-1.32), the HR for multiple spontaneous abortions was 1.37 (95% CI 1.20-1.58), and the HR for a single spontaneous abortion was 1.17 (95% CI 1.07-1.28). The risks were similar regardless of whether spontaneous abortion occurred before or after the index delivery. Estimates were nearly unchanged after adjusting for preterm birth, low birthweight, or Apgar score.

Interpretation: Children born to mothers with spontaneous abortion, especially multiple spontaneous abortions, may be at a higher risk of intellectual disability in later life, regardless of whether spontaneous abortion occurred before or after the index delivery. The findings have clinical implications for targeted early intervention of children with intellectual disability.
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http://dx.doi.org/10.1111/dmcn.14839DOI Listing
February 2021

Comprehensive Characterization of Immunological Profiles and Clinical Significance in Hepatocellular Carcinoma.

Front Oncol 2020 22;10:574778. Epub 2021 Jan 22.

Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Therapies targeting immune molecules have rapidly been adopted and advanced the treatment of hepatocellular carcinoma (HCC). Nonetheless, no studies have reported a systematic analysis between immunological profiles and clinical significance in HCC.

Methods: We comprehensively investigated immune patterns and systematically correlated 22 types of both adaptive and innate immune cells with genomic characteristics and clinical outcomes based on 370 HCC patients from The Cancer Genome Atlas (TCGA) database through a metagene approach (known as CIBERSORT). Based on the coupled with integrated high-dimensional bioinformatics analysis, we further independently validated six immune subsets (CD4 T cells, CD8 T cells, CD20 B cells, CD14 monocytes, CD56 NK cells, and CD68 macrophages), and shortlisted three (CD4 T cells, CD8 T cells, and CD56 NK cells) of which to investigate their association with clinical outcomes in two independent Zhongshan cohorts of HCC patients (n = 258 and n = 178). Patient prognosis was further evaluated by Kaplan-Meier analysis and univariate and multivariate regression analysis.

Results: By using the CIBERSORT method, the immunome landscape of HCC was constructed based on integrated transcriptomics analysis and multiplexed sequential immunohistochemistry. Further, the patients were categorized into four immune subgroups featured with distinct clinical outcomes. Strikingly, significant inter-tumoral and intra-tumoral immune heterogeneity was further identified according to the in-depth interrogation of the immune landscape.

Conclusion: This work represents a potential useful resource for the immunoscore establishment for prognostic prediction in HCC patients.
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http://dx.doi.org/10.3389/fonc.2020.574778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862794PMC
January 2021

A Spatial Ecological Study on Hair Selenium Level of Residents in Keshan Disease Endemic and Non-endemic Areas in Heilongjiang Province, China.

Biol Trace Elem Res 2021 Feb 3. Epub 2021 Feb 3.

Institute of Keshan Disease, Chinese Center for Endemic Disease Control, Harbin Medical University, 157 Baojian Road, Harbin, 150081, China.

This study was aimed to provide, by mapping the spatial distribution of hair selenium levels of residents, visualized evidence for assessment of KD elimination from a perspective of selenium nutrition of the residents living in the KD-endemic and non-endemic areas. Using a spatial ecological research design, 401 male permanent residents in KD-endemic and non-endemic areas participated in this study. Demographic information and hair samples were obtained through a questionnaire survey and sample collection, respectively. Hair selenium was measured using hydride generation atomic fluorescence spectrometry. Thematic maps were created, and spatial analysis was conducted using ArcGIS 9.0. The median of hair selenium of the participants was 0.30 (IQR, 0.23-0.34) mg/kg. The median hair selenium of the residents in the KD-endemic areas was significantly lower than that of the residents of the non-endemic areas. The hair selenium levels of residents were spatially clustered, with cold spots and hot spots located in northwest and southwest regions respectively. Residents living in KD-endemic areas may still have selenium deficiency. Measuring hair selenium levels of residents in KD-endemic areas as a molecular marker of selenium nutritional status as part of KD surveillance could provide visualized evidence for the evaluation of KD elimination from a perspective of selenium nutrition of the residents living in the KD endemic areas.
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http://dx.doi.org/10.1007/s12011-021-02609-1DOI Listing
February 2021

The KRAS and other prenylated polybasic domain membrane anchors recognize phosphatidylserine acyl chain structure.

Proc Natl Acad Sci U S A 2021 Feb;118(6)

Department of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center, Houston, TX 77030;

KRAS interacts with the inner leaflet of the plasma membrane (PM) using a hybrid anchor that comprises a lysine-rich polybasic domain (PBD) and a C-terminal farnesyl chain. Electrostatic interactions have been envisaged as the primary determinant of interactions between KRAS and membranes. Here, we integrated molecular dynamics (MD) simulations and superresolution spatial analysis in mammalian cells and systematically compared four equally charged KRAS anchors: the wild-type farnesyl hexa-lysine and engineered mutants comprising farnesyl hexa-arginine, geranylgeranyl hexa-lysine, and geranylgeranyl hexa-arginine. MD simulations show that these equally charged KRAS mutant anchors exhibit distinct interactions and packing patterns with different phosphatidylserine (PtdSer) species, indicating that prenylated PBD-bilayer interactions extend beyond electrostatics. Similar observations were apparent in intact cells, where each anchor exhibited binding specificities for PtdSer species with distinct acyl chain compositions. Acyl chain composition determined responsiveness of the spatial organization of different PtdSer species to diverse PM perturbations, including transmembrane potential, cholesterol depletion, and PM curvature. In consequence, the spatial organization and PM binding of each KRAS anchor precisely reflected the behavior of its preferred PtdSer ligand to these same PM perturbations. Taken together these results show that small GTPase PBD-prenyl anchors, such as that of KRAS, have the capacity to encode binding specificity for specific acyl chains as well as lipid headgroups, which allow differential responses to biophysical perturbations that may have biological and signaling consequences for the anchored GTPase.
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http://dx.doi.org/10.1073/pnas.2014605118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017956PMC
February 2021