Publications by authors named "Xiang Fang"

382 Publications

Indoles as essential mediators in the gut-brain axis. Their role in Alzheimer's disease.

Neurobiol Dis 2021 Jun 1;156:105403. Epub 2021 Jun 1.

Quiris Health, Gütersloh, Germany.

Sporadic late-onset Alzheimer's disease (AD) is the most frequent cause of dementia associated with aging. Due to the progressive aging of the population, AD is becoming a healthcare burden of unprecedented proportions. Twenty years ago, it was reported that some indole molecules produced by the gut microbiota possess essential biological activities, including neuroprotection and antioxidant properties. Since then, research has cemented additional characteristics of these substances, including anti-inflammatory, immunoregulatory, and amyloid anti-aggregation features. Herein, we summarize the evidence supporting an integrated hypothesis that some of these substances can influence the age of onset and progression of AD and are central to the symbiotic relationship between intestinal microbes and the brain. Studies have shown that some of these substances' activities result from interactions with biologically conserved pathways and with genetic risk factors for AD. By targeting multiple pathologic mechanisms simultaneously, certain indoles may be excellent candidates to ameliorate neurodegeneration. We propose that management of the microbiota to induce a higher production of neuroprotective indoles (e.g., indole propionic acid) will promote brain health during aging. This area of research represents a new therapeutic paradigm that could add functional years of life to individuals who would otherwise develop dementia.
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http://dx.doi.org/10.1016/j.nbd.2021.105403DOI Listing
June 2021

In-depth analysis reveals complex molecular aetiology in a cohort of idiopathic cerebral palsy.

Brain 2021 Jun 2. Epub 2021 Jun 2.

Laboratory of Medical Systems Biology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 510623, Guangzhou, China.

Cerebral palsy is the most prevalent physical disability in children; however, its inherent molecular mechanisms remain unclear. In the present study, we performed in-depth clinical and molecular analysis on 120 idiopathic cerebral palsy families, and identified underlying detrimental genetic variants in 45% of these patients. In addition to germline variants, we found disease-related postzygotic mutations in approximately 6.7% of cerebral palsy patients. We found that patients with more severe motor impairments or a comorbidity of intellectual disability had a significantly higher chance of harboring disease-related variants. By a compilation of 114 known cerebral-palsy-related genes, we identified characteristic features in terms of inheritance and function, from which we proposed a dichotomous classification system according to the expression patterns of these genes and associated cognitive impairments. In two patients with both cerebral palsy and intellectual disability, we revealed that the defective TYW1, a tRNA hypermodification enzyme, caused primary microcephaly and problems in motion and cognition by hindering neuronal proliferation and migration. Furthermore, we developed an algorithm and demonstrated in mouse brains that this malfunctioning hypermodification specifically perturbed the translation of a subset of proteins involved in cell cycling. This finding provided a novel and interesting mechanism for congenital microcephaly. In another cerebral palsy patient with normal intelligence, we identified a mitochondrial enzyme GPAM, the hypomorphic form of which led to hypomyelination of the corticospinal tract in both human and mouse models. In addition, we confirmed that the aberrant Gpam in mice perturbed the lipid metabolism in astrocytes, resulting in suppressed astrocytic proliferation and a shortage of lipid contents supplied for oligodendrocytic myelination. Taken together, our findings elucidate novel aspects of the etiology of cerebral palsy and provide insights for future therapeutic strategies.
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http://dx.doi.org/10.1093/brain/awab209DOI Listing
June 2021

Homozygous mutation in causes autosomal recessive primary microcephaly and intellectual disability.

J Med Genet 2021 May 31. Epub 2021 May 31.

Institute of Cell Biology and Neurobiology, Charité Universitätsmedizin Berlin, Berlin, Germany

Background: Minichromosomal maintenance (MCM) complex components 2, 4, 5 and 6 have been linked to human disease with phenotypes including microcephaly and intellectual disability. The MCM complex has DNA helicase activity and is thereby important for the initiation and elongation of the replication fork and highly expressed in proliferating neural stem cells.

Methods: Whole-exome sequencing was applied to identify the genetic cause underlying the neurodevelopmental disease of the index family. The expression pattern of was characterised by performing quantitative real-time PCR, hybridisation and immunostaining. To prove the disease-causative nature of identified , a proof-of-principle experiment was performed.

Results: We reported that the homozygous missense variant c.793G>A/p.A265T (g.7:99695841C>T, NM_005916.4) in was associated with autosomal recessive primary microcephaly (MCPH), severe intellectual disability and behavioural abnormalities in a consanguineous pedigree with three affected individuals. We found concordance between the spatiotemporal expression pattern of in mice and a proliferative state: expression was higher in early mouse developmental stages and in proliferative zones of the brain. Accordingly, Mcm7/MCM7 levels were detectable particularly in undifferentiated mouse embryonal stem cells and human induced pluripotent stem cells compared with differentiated neurons. We further demonstrate that the downregulation of in mouse neuroblastoma cells reduces cell viability and proliferation, and, as a proof-of-concept, that this is counterbalanced by the overexpression of wild-type but not mutant .

Conclusion: We report mutations of as a novel cause of autosomal recessive MCPH and intellectual disability and highlight the crucial function of MCM7 in nervous system development.
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http://dx.doi.org/10.1136/jmedgenet-2020-107518DOI Listing
May 2021

Recurrent perimesencephalic nonaneurysmal subarachnoid hemorrhage within a short period of time: A case report.

World J Clin Cases 2021 May;9(14):3356-3364

Department of Neurosurgery, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan 250000, Shandong Province, China.

Background: Spontaneous subarachnoid hemorrhage (SAH) is primarily caused by a ruptured intracranial aneurysm. Perimesencephalic nonaneurysmal SAH (PNSAH) accounts for approximately 5% of all spontaneous SAH. PNSAH displays favorable prognosis. The risk of hemorrhage recurrence is low. We report a case of PNSAH recurrence, occurring within a short time after the initial episode in a patient not receiving antithrombotic or antiplatelet drugs.

Case Summary: A 66-year-old male, without any history of recent trauma or antithrombotic/ antiplatelet medication, suffered two similar episodes of sudden onset of severe headache, nausea, and vomiting. A plain head computed tomography (CT) scan showed subarachnoid blood confined to the anterior part of the brainstem. Platelet count and coagulation function were normal. PNSAH was diagnosed by repeated head CT, magnetic resonance imaging, and cerebral angiography, none of which revealed the source of SAH. The patient was discharged without focal neurological deficits. At 6-mo follow-up, the patient had experienced no sudden onset of severe headache and presented favorable clinical outcome. Studies have reported a few patients with recurrent PNSAH, originating frequently from venous hemorrhage and conventionally associated with venous abnormalities. PNSAH recurs within a short time following the initial onset of symptoms, although the possibility of re-hemorrhage is extremely rare.

Conclusion: PNSAH recurrence should arouse vigilance; however, the definite source of idiopathic SAH in this case report deserves further attention.
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http://dx.doi.org/10.12998/wjcc.v9.i14.3356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107889PMC
May 2021

Corrigendum: Effect of a Humanized Diet Profile on Colonization Efficiency and Gut Microbial Diversity in Human Flora-Associated Mice.

Front Nutr 2021 26;8:676085. Epub 2021 Apr 26.

College of Food Science, South China Agricultural University, Guangzhou, China.

[This corrects the article DOI: 10.3389/fnut.2021.633738.].
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http://dx.doi.org/10.3389/fnut.2021.676085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107682PMC
April 2021

Viral dynamics and antibody responses in people with asymptomatic SARS-CoV-2 infection.

Signal Transduct Target Ther 2021 05 10;6(1):181. Epub 2021 May 10.

State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China.

Over 40% of the coronavirus disease 2019 (COVID-19) COVID-19 patients were asymptomatically infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the immune responses of these asymptomatic individuals is a critical factor for developing the strategy to contain the COVID-19 pandemic. Here, we determined the viral dynamics and antibody responses among 143 asymptomatic individuals identified in a massive screening of more than 5 million people in eight districts of Wuhan in May 2020. Asymptomatic individuals were admitted to the government-designated centralized sites in accordance with policy. The incidence rate of asymptomatic infection is ~2.92/100,000. These individuals had low viral copy numbers (peaked at 315 copies/mL) and short-lived antibody responses with the estimated diminish time of 69 days. The antibody responses in individuals with persistent SARS-CoV-2 infection is much longer with the estimated diminish time of 257 days. These results imply that the immune responses in the asymptomatic individuals are not potent enough for preventing SARS-CoV-2 re-infection, which has recently been reported in recovered COVID-19 patients. This casts doubt on the efficacy of forming "herd-immunity" through natural SARS-CoV-2 infection and urges for the development of safe and effective vaccines.
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http://dx.doi.org/10.1038/s41392-021-00596-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107204PMC
May 2021

Multi-omics analyses on the response mechanisms of 'Shine Muscat' grapevine to low degree of excess copper stress (Low-ECS).

Environ Pollut 2021 Apr 30;286:117278. Epub 2021 Apr 30.

Department of Horticulture, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China; Fruit Crop Genetic Improvement and Seedling Propagation Engineering Center of Jiangsu Province, Nanjing, 210095, China.

Copper stress is one of the most severe heavy metal stresses in plants. Grapevine has a relatively higher copper tolerance than other fruit crops. However, there are no reports regarding the tolerance mechanisms of the 'Shine Muscat' ('SM') grape to a low degree of excess copper stress (Low-ECS). Based on the physiological indicators and multi-omics (transcriptome, proteome, metabolome, and microRNAome) data, 8 h (h) after copper treatment was the most severe stress time point. Nonetheless, copper stress was alleviated 64 h after treatment. Cu ion transportation, photosynthesis pathway, antioxidant system, hormone metabolism, and autophagy were the primary response systems in 'SM' grapevine under Low-ECS. Numerous genes and proteins, such as HMA5, ABC transporters, PMM, GME, DHAR, MDHAR, ARGs, and ARPs, played essential roles in the 'SM' grapevine's response to Low-ECS. This work was carried out to gain insights into the multi-omics responses of 'SM' grapevine to Low-ECS. This study provides genetic and agronomic information that will guide better vinery management and breeding copper-resistant grape cultivars.
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http://dx.doi.org/10.1016/j.envpol.2021.117278DOI Listing
April 2021

mA demethylase ALKBH5 suppresses proliferation and migration of enteric neural crest cells by regulating TAGLN in Hirschsprung's disease.

Life Sci 2021 Aug 5;278:119577. Epub 2021 May 5.

Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing 210000, Jiangsu, China. Electronic address:

Objectives: This study aims to investigate the role of demethylase ALKBH5 mediated demethylation of TAGLN mRNA in the occurrence of Hirschsprung's disease (HSCR), and to clarify how ALKBH5 reduces the mA level of TAGLN mRNA and inhibits its degradation, thereby inhibiting the proliferation and migration of neural crest cells, and potentially contributing to the occurrence of HSCR.

Material And Methods: Quantitative real-time PCR (qRT-PCR) and Western-Blot (WB) were conducted to test the expression level of ALKBH5 and TAGLN genes. Cell function assays were adopted to detect cell phenotypes. The qRT-PCR and methylated RNA immunoprecipitation (MeRIP-qPCR) were used to test the regulation of TAGLN by ALKBH5.

Results: 1. Compared with control intestinal tissue, the expression level of TAGLN and ALKBH5 in the aganglionic intestinal tissue of HSCR is increased. 2. The MeRIP-PCR and dualluciferase report confirmed that ALKBH5 could bind to mA sites of TAGLN mRNA and reduce the mA level of TAGLN mRNA. 3. In vitro cell experiments confirmed that overexpression of ALKBH5 can inhibit the degradation of TAGLN mRNA, increase the expression of TAGLN, thereby inhibiting cell proliferation and migration. 4. A zebrafish model of ALKBH5 overexpression was constructed. Studies have shown that ALKBH5 could inhibit the proliferation and migration of zebrafish enteric neurons.

Conclusions: ALKBH5 could demethylate TAGLN mRNA and up-regulate TAGLN expression, leading to the inhibition of proliferation and migration of enteric neural crest cells and contributing to the occurrence of HSCR.
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http://dx.doi.org/10.1016/j.lfs.2021.119577DOI Listing
August 2021

Using MEST-C Scores and the International Study of Kidney Disease in Children Classification to Predict Outcomes of Henoch-Schönlein Purpura Nephritis in Children.

Front Pediatr 2021 14;9:658845. Epub 2021 Apr 14.

Department of Pediatrics, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, China.

Henoch-Schönlein purpura nephritis (HSPN) and IgA nephropathy (IgAN) bear similarities in some aspects. The histological classification of HSPN was built on the International Study of Kidney Disease in Children (ISKDC) criteria, while IgAN was established on the 2016 Oxford classification (MEST-C scores). The purpose of this paper was to discuss the predictive value of the ISKDC classification and MEST-C scores in children with HSPN. We performed a retrospective study of 877 children with HSPN in a single center between 2001 and 2019. The primary outcome was defined as chronic kidney disease-estimated glomerular filtration rate (eGFR) <90 ml/min/1.73 m. During the follow-up period of 23.3 (10.9-47.9) months, 51 (5.8%) patients reached the primary outcome. As revealed in a Kaplan-Meier plot, segmental glomerulosclerosis (S) ( < 0.001) and tubular atrophy/interstitial fibrosis (T) ( < 0.001) significantly predict poor renal outcome. Other Oxford lesions and the ISKDC classification, however, did not show a significant difference in a worse outcome. In a multivariate Cox model adjusted for pathological and clinical factors, eGFR [hazard ratio (HR) = 2.831, 95% confidence interval (95% CI) = 1.359-5.896], S lesion (HR = 3.936, 95% CI = 2.078-7.457), and T lesion (HR = 4.002, 95% CI = 1.733-9.242) were independent risk factors for the renal outcome. This series constitutes the largest series reported so far in the literature of such patients. According to our findings, S and T of the Oxford classification, which are ignored by the ISKDC classification, could be applied to predict the renal prognosis of children with HSPN.
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http://dx.doi.org/10.3389/fped.2021.658845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079736PMC
April 2021

The distribution and epidemic characteristics of cerebrovascular disease in followed-up hypertension patients.

Sci Rep 2021 Apr 30;11(1):9366. Epub 2021 Apr 30.

Jiading District Center for Disease Control and Prevention, Shanghai, China.

To explore distribution and epidemic characteristics of CVD in followed-up HP patients. Using the Hypertension Follow-up Management System database in Jiading district in Shanghai. We designed a retrospective cohort study that included all followed-up hypertension patients between 2002 and 2020. The endpoint was the occurrence of CVD confirmed by the hospital; otherwise, the patients were tracked until September 30, 2020. Record information of every patient has been collected in the registration card and each followed-up record. Among 223,097 observational followed-up HP patients, the total number of person years of observation was 4,244,421.25 person-year, 11,143 patients had developed CVD from hypertension before the deadline, the total incidence density was 0.00263 per person-year (male 0.00292; female 0.00238) and the complication ratio of CVD in HP patients was 4.99% (male 5.25%; female 4.76%) during follow-up period. The proportion of ischemic cerebrovascular, hemorrhagic cerebrovascular and unclassified stroke was respectively 71.18%, 5.95% and 22.87% in hypertensive CVD. Complication ratio of CVD increased with age, the group under 30 was 0, and the group over 70 was the highest (6.90%). The complication ratio of grad I, grad II and grad III blood pressure were respectively 4.79%, 4.96% and 6.13%. The complication ratio was 4.92% in only high systolic blood pressure patients; 17.23% in only high diastolic blood pressure patients; 4.59% in high systolic and diastolic blood pressure patients. The peak of complication ratio of CVD was 9-10 years after the registered and followed-up. The proportion of CVD cases in HP patients from April to June was the largest in the four seasons; the proportion of patients from October to December was the minimum. HP patient was prone to falling cerebrovascular disease; the main type of disease was cerebral infarction. Complication ratio in male incidence was higher than that in female. The complication ratio of CVD increased with age, blood pressure and duration of HP patients. It had seasonal characteristics, which was relatively high from April to June within year.
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http://dx.doi.org/10.1038/s41598-021-88127-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087808PMC
April 2021

Isolation and identification of a human intestinal bacterium capable of daidzein conversion.

FEMS Microbiol Lett 2021 May;368(8)

College of Food Science, South China Agricultural University, Guangzhou, China.

Equol, which produced from daidzein (one of the principal isoflavones), is recognized to be the most resultful in stimulating an estrogenic and antioxidant response. The daidzein transformation was studied during fermentation of five growth media inoculated with feces from a healthy human, and a daidzein conversion strain was isolated. To enrich the bacterial population involved in daidzein metabolism in a complex mixture, fecal samples were treated with antibiotics. The improved propidium monoazide combined with the quantitative polymerase chain reaction (PMAxx-qPCR) assay showed that the ampicillin treatment of samples did result in a reduction of the total visible bacteria counts by 52.2% compared to the treatment without antibiotics. On this basis, the newly isolated rod-shaped, Gram-positive anaerobic bacterium, named strain Y11 (MN560033), was able to metabolize daidzein to equol under anaerobic conditions, with a conversion ratio (equol ratio: the amount of equol produced/amount of supplemented daizein) of 0.56 over 120 h. The 16S rRNA partial sequence of the strain Y11 exhibited 99.8% identity to that of Slackia equolifaciens strain DZE (NR116295). This study will provide new insights into the biotransformation of equol from daidzein by intestinal microbiota from the strain-level and explore the possibility of probiotic interventions.
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http://dx.doi.org/10.1093/femsle/fnab046DOI Listing
May 2021

Pelvic Reconstruction With a Novel Three-Dimensional-Printed, Multimodality Imaging Based Endoprosthesis Following Enneking Type I + IV Resection.

Front Oncol 2021 13;11:629582. Epub 2021 Apr 13.

West China School of Medicine/West China Hospital, Sichuan University, Chengdu, China.

Background And Purpose: Pelvic tumor involving Type I + IV resections are technically challenging, along with various reconstructions methods presenting unsatisfactory outcomes and high complication rates. Since predominating studies preferred adopting pedicle screw-rod system (PRSS) to address this issue, we designed a novel three-dimensional-printed, multimodality imaging (3DMMI) based endoprosthesis with patient-specific instrument (PSI) assistance to facilitate the surgical reconstruction of pelvic tumor involving Enneking Type I + IV resection. We aimed to investigate the clinical effectiveness of this novel endoprosthesis and compare it with PRSS in Type I + IV reconstruction.

Methods: We retrospective studied 28 patients for a median follow-up of 47 months (range, 10 to 128 months) in this study with either 3D-printed endoprosthesis reconstruction (n = 10) or PRSS reconstruction (n = 18) between January 2000 and December 2017. Preoperative 3DMMI technique was used for tumor evaluation, PSI design, virtual surgery, and endoprosthesis fabrication. Clinical, oncological outcomes, functional assessments, and complications were analyzed between the two groups.

Results: Minor surgical trauma with mean operative duration of 251 ± 52.16 minutes (p = 0.034) and median intraoperative hemorrhage of 2000ml (range, 1600, 4000ml) (p = 0.032) was observed in endoprosthesis group. Wide margins were achieved in 9 patients of the endoprosthesis group compared with 10 in the PRSS group (p = 0.09). The 1993 version of the Musculoskeletal Tumor Society score (MSTS-93) was 23.9 ± 3.76 in endoprosthesis group, which was higher than PRSS group (p = 0.012). No statistical significance was found in relapse between two groups (p = 0.36). Complications were observed in two patients in endoprosthesis group compared with 12 patients in PRSS group (p = 0.046).

Conclusion: The novel design of this 3D-printed endoprosthesis, together with 3DMMI and PSI assisted, is technically accessible with favorable clinical outcomes compared with PRSS. Further study is essential to identify its long-term outcomes.
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http://dx.doi.org/10.3389/fonc.2021.629582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078592PMC
April 2021

Bi-allelic mutation in Fsip1 impairs acrosome vesicle formation and attenuates flagellogenesis in mice.

Redox Biol 2021 Jul 16;43:101969. Epub 2021 Apr 16.

Laboratory of Medical Systems Biology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 510623, Guangzhou, China. Electronic address:

Fibrous sheath interacting protein 1 (Fsip1) is a cytoskeletal structural protein of the sperm flagellar proteome. A few studies have reported that it plays a vital role in the tumorigenesis and cancer progression. However, little is known about the role of Fsip1 in spermatogenesis and mammalian sperm flagellogenesis. Fsip1 protein showed the highest expression in round spermatids, and was translocated from nucleus to the anterior region of the elongating spermatid head. To investigate its role we constructed homozygous Fsip1 null (Fsip1) mice. We found that the homozygous Fsip1 mutant mice were infertile, with a low sperm count and impaired motility. Interestingly, a subtle phenotype characterized by abnormal head shape, and flagella deformities was observed in the sperm of Fsip1 mutant mice similar to the partial globozoospermia phenotype. Electron microscopy analysis of Fsip1 sperm revealed abnormal accumulation of mitochondria, disrupted axoneme and retained cytoplasm. Testicular sections showed increased cytoplasmic vacuoles in the elongated spermatid of Fsip1mice, which indicated an intraflagellar transport (IFT) defect. Using proteomic approaches, we characterized the cellular components and the mechanism underlying this subtle phenotype. Our result indicated that Fsip1downregulates the formation of acrosomal membrane and vesicles proteins, intraflagellar transport particles B, and sperm flagellum components. Our results suggest that Fsip1 is essential for normal spermiogenesis, and plays an essential role in the acrosome biogenesis and flagellogenesis by attenuating intraflagellar transport proteins.
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http://dx.doi.org/10.1016/j.redox.2021.101969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099781PMC
July 2021

Zebrafish modeling mimics developmental phenotype of patients with RAPGEF1 mutation.

Clin Genet 2021 Apr 9. Epub 2021 Apr 9.

Laboratory of Medical Systems Biology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

RAPGEF1 is a guanine nucleotide exchange factor responsible for transmitting extracellular signals to the Ras family of GTPase located at the inside of membrane. Here, we report for the first time a homozygous mutation of RAPGEF1 in a consanguineous family with two siblings affected by neuropsychiatric disorder. To confirm the correlation of the mutation and the phenotype, we utilized in silico analysis and established a zebrafish model. Survival rate was reduced in the rapgef1a-knockdown model, and the zebrafish showed global morphological abnormalities, particularly of brain and blood vessels. Co-application of human RAPGEF1 wildtype mRNA effectively rescued the abnormal phenotype, while that of RAPGEF1 mRNA carrying the human mutation did not. This work is the first report of a human Mendelian disease associated with RAPGEF1 and the first report of a zebrafish model built for this gene. The phenotype of zebrafish model provides further evidence that defective RAPGEF1 may lead to global developmental delay in human patients.
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http://dx.doi.org/10.1111/cge.13965DOI Listing
April 2021

Direct distinction of ibuprofen and flurbiprofen enantiomers by ion mobility mass spectrometry of their ternary complexes with metal cations and cyclodextrins in the gas phase.

J Sep Sci 2021 Apr 6. Epub 2021 Apr 6.

Zhejiang Provincial Key Laboratory of Advanced Mass Spectrometry and Molecular Analysis, Institute of Mass Spectrometry, School of Materials Science and Chemical Engineering, Ningbo University, Ningbo, P. R. China.

Enantiomeric drugs are widely used and play important roles in pharmaceuticals. Ion mobility spectrometry coupled with mass spectrometry technology provides a unique method for distinguishing the enantiomeric drugs, enantiomeric identification, and quantitation in the gas phase. In this study, enantiomeric molecules of ibuprofen and flurbiprofen were clearly recognized by forming host-guest complex ions using trapped ion mobility time-of-flight mass spectrometry. Ternary complex ions can be produced easily by electrospray ionization of the mixed solutions of ibuprofen, cyclodextrins, and CaCl , LiCl, or NaCl, as well as flurbiprofen, cyclodextrins, and CaCl . The relative contents of different chiral ibuprofens in a mixed solution were also quantitatively measured. This new method is a simple, effective, and a convenient enantioselective analysis method.
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http://dx.doi.org/10.1002/jssc.202100025DOI Listing
April 2021

DIAGNOSTIC CHARACTERISTICS OF B-SCAN SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY FOR PATIENTS WITH POLYPOIDAL CHOROIDAL VASCULOPATHY.

Retina 2021 Mar 30. Epub 2021 Mar 30.

Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China; Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education Department of Epidemiology and Health Statistics, West China School of Public Health, Sichuan University, Chengdu, Sichuan, People's Republic of China.

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http://dx.doi.org/10.1097/IAE.0000000000003172DOI Listing
March 2021

Improving the performance of proteomic analysis via VAILase cleavage and 193-nm ultraviolet photodissociation.

Anal Chim Acta 2021 Apr 20;1155:338340. Epub 2021 Feb 20.

CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

Further improving the proteomic identification coverage and reliability is still challenging in the mass spectrometry (MS)-based proteomics. Herein, we combine VAILase and trypsin digestion with 193-nm ultraviolet photodissociation (UVPD) and higher-energy collision dissociation (HCD) to improve the performance of bottom-up proteomics. As VAILase exhibits high complementarity to trypsin, the proteome sequence coverage is improved obviously whether with HCD or 193-nm UVPD. The high diversity of fragment ion types produced by UVPD contributes to the improvements of identification reliability for both trypsin- and VAILase-digested peptides with an average XCorr score improvement of 10%.
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http://dx.doi.org/10.1016/j.aca.2021.338340DOI Listing
April 2021

Insulin Resistance is Associated with Central Pain in Patients with Fibromyalgia.

Pain Physician 2021 Mar;24(2):175-184

Pain and Headache Center, Eagle River, Alaska.

Background: Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to insulin. IR has been associated with multiple conditions, including chronic pain. Fibromyalgia (FM) is one of the common generalized chronic painful conditions with an incidence rate affecting 3% to 6% of the population. Substantial interest and investigation into FM continue to generate  many hypotheses.The relationship between IR and FM has not been explored. IR is known to cause abnormalities in the cerebral microvasculature, leading to focal hypoperfusion. IR also has been shown to cause cognitive impairment in FM patients, as in parkinsonism. As demonstrated by advanced imaging methods, similar brain perfusion abnormalities occur in the brain of patients with FM as with IR.

Objectives: To determine the potential association between FM and IR.

Setting: Subspecialty pain medicine clinics.

Study Design: Observational cross-sectional study.

Methods: Laboratory data was extracted through a retrospective review of medical records from patients who had met the American College of Rheumatology (ACR) criteria for FM. The Hemoglobin A1c (HbA1c) values from 33 patients with FM were compared with the means of the glycated HbA1c levels of 2 control populations. In addition, established indices of IR [Quantitative Insulin Sensitivity Check Index (QUICKI) and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)] were calculated in a subgroup of patients in whom the analytes necessary for these calculations were available. To assess for confounding factors, the associations between HbA1c, QUICKI, HOMA-IR, fasting insulin levels, and glucose, after controlling for age, were explored by multiple analyses of variance with relation to gender and ethnicity.

Results: We found an association between IR and FM that was independent of age, gender, and ethnicity. We found that patients with FM belong to a distinct population that can be segregated from the control groups by their HbA1c levels, a surrogate marker of IR. This was demonstrated by analyzing the data after introducing an age correction into a linear regression model. This strategy showed significant differences between patients with FM and control subjects (P < 0.0001 and P  = 0.0002, for 2 separate control populations, respectively). A subgroup analysis using the QUICKI and HOMA-IR showed that all patients with FM in this subgroup (100%) exhibited laboratory abnormalities pointing to IR.

Limitations: Small observational cross-sectional study. There are also intrinsic limitations that are attributed to cross-sectional studies.

Conclusion: The association demonstrated in this study warrant further investigation, including the pursuit of randomized, double-blind clinical trials to determine the effect of improving insulin sensitivity in FM related pain scores. Such studies could unveil a potential pathogenetic relationship between FM, central pain, and IR. Based on these initial findings, we present the hypothesis that IR may underlie pathological mechanisms leading to central pain. If confirmed, this may lead to a paradigm shift in the management of central pain.
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March 2021

Effect of a Humanized Diet Profile on Colonization Efficiency and Gut Microbial Diversity in Human Flora-Associated Mice.

Front Nutr 2021 23;8:633738. Epub 2021 Feb 23.

College of Food Science, South China Agricultural University, Guangzhou, China.

Human flora-associated (HFA) mouse models allow us to design interventions for human disease research to test specific hypotheses and explore the complex commensal microbiome while avoiding the ethical limitations of using humans as models to directly study intestinal flora diseases. However, few studies have investigated the effect of a humanized diet profile (coarse-feed diet; CFD) on colonization efficiency and gut microbial diversity in HFA mice. We tested the colonization efficiency and gut microbial diversity in germ-free Kunming (KM) mice fed a CFD or a purified feed diet (PFD) at 1, 2, and 4 weeks. Although the colonization efficiencies differed significantly (67.50-70.00% vs. 72.69-85.96%) in the HFA mice, the colonization efficiency of the PFD-fed HFA mice (85.96%) was significantly higher than that of the CFD-fed mice (69.61%) at 2 weeks. At 4 weeks, the colonization efficiency of the PFD-fed mice (72.69%) was comparable to that of the CFD-fed mice (70.00%). Additionally, the gut microbial diversity of the CFD-fed HFA mice was similar to that of a human fecal donor. Regarding the Kyoto Encyclopedia of Genes and Genomes colonic microbiota metabolic pathways, the CFD-fed HFA mice showed more similarities to the human donor than to the PFD-fed mice in amino sugar and nucleotide sugar metabolism, biosynthesis of amino acids, carbon metabolism, purine metabolism, and phosphotransferase systems. In conclusion, the humanized diet profiles of the CFD and PFD could help establish human microbiotas in mice. Constructing HFA mouse models fed a CFD for 4 weeks may be useful in researching human-derived intestinal diseases.
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http://dx.doi.org/10.3389/fnut.2021.633738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940529PMC
February 2021

Direct and simultaneous recognition of the positional isomers of aminobenzenesulfonic acid by TIMS-TOF-MS.

Talanta 2021 May 7;226:122085. Epub 2021 Jan 7.

Zhejiang Provincial Key Laboratory of Advanced Mass Spectrometry and Molecular Analysis, Institute of Mass Spectrometry, School of Material Science and Chemical Engineering, Ningbo University, Ningbo, Zhejiang, 315211, China. Electronic address:

Positional isomer recognition is a challenging scientific issue. Fast and accurate detection of isomers is required for understanding their chemical properties. Here, we describe a method for simultaneous recognition of three positional isomers of 2-aminobenzenesulfonic acid (2-ABSA), 3-ABSA, and 4-ABSA using trapped ion mobility spectroscopy-time-of-flight mass spectrometry (TIMS-TOF-MS). The three ABSA positional isomers were recognized by measuring the different ion mobility of the ternary complexes of [β-cyclodextrin (CD)+ABSA + Li] or [λ-CD + ABSA + Na], because their different collision cross-sections or different spatial conformations. The collision-induced dissociation mechanism of the different complexes of [β-CD + ABSA + Li] and [λ-CD + ABSA + Na] using tandem mass spectrometry exhibited the same dissociation process with slightly different dissociation energies, which the smaller cross-section requires higher collision energy that means the smaller complex with tighter and more stable conformation than a larger complex for the ABSA complexes. In addition, relative quantification of the ABSA isomers was studied by measuring any two of the three ABSA isomer complexes at different molar ratio of 10:1 to 1:10 in the μM range, good linearity (R > 0.99) with precision between 2.14% and 2.58%, and accuracy ≥ 97.1% were obtained. The method for fast determination and recognition of ABSA positional isomers by combination with CD and alkali metal ions possesses the advantages of being simple, direct, rapid, sensitive, cost-effective, and needs no chemical derivatives or chromatographic separation before analysis. Therefore, the proposed method would be a powerful tool for the analysis of ABSA isomers or even other positional isomers.
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http://dx.doi.org/10.1016/j.talanta.2021.122085DOI Listing
May 2021

Post-Treating the Precursor Intermediate Film by a Cooling Stage for Fabricating Efficient Formamidinium-Based Perovskite Solar Cells.

ACS Appl Mater Interfaces 2021 Mar 3;13(10):11783-11792. Epub 2021 Mar 3.

School of Materials Science and Engineering, Jiangsu Collaborative Innovation Center for Photovoltaic Science and Engineering, Jiangsu Province Cultivation Base for State Key Laboratory of Photovoltaic Science and Technology, Changzhou University, Changzhou 213164, Jiangsu, P. R. China.

Formamidinium lead iodide (FAPbI) is a category of perovskite material with an ideal band gap and high thermal stability, which can be efficiently prepared by two-step spin-coating. Spin-coating organic salts and transforming intermediate phase at the second step involves a components' reaction and state transition, thus playing a crucial role in the film quality formed afterward and optoelectronic properties of the fabricated perovskite solar cells (PSCs). In this paper, a cooling stage (CO) is used to post-treat the as-prepared precursor after the second spin-coating. The procedure of intermediate phase transferring to other state is found to be retarded; hence, the appearing velocity of perovskite nucleation is decreased. As a result, components react more adequately and larger perovskite grains with fewer defects are obtained; charge transport as well as carrier recommbination behaviors are therefore optimized. The PSCs based on the CO process achieved a champion power conversion efficiency (PCE) of 21.51% with enhanced stability. Moreover, CO treatment is observed to be beneficial for improving the film quality of perovskite in large-area preparation, which we anticipate can be further extended to the commercialized application of PSCs.
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http://dx.doi.org/10.1021/acsami.0c20126DOI Listing
March 2021

The interaction on hypertension between family history and diabetes and other risk factors.

Sci Rep 2021 Feb 25;11(1):4716. Epub 2021 Feb 25.

Jiading District Center for Disease Control and Prevention, Shanghai, China.

To explore the individual effect and interaction of diabetes and family history and other risk factors on hypertension in Han in Shanghai China. The method of case-control study with l:l matched pairs was used, 342 cases of hypertension and 342 controls were selected and investigate their exposed factors with face-to-face. The method of epidemiology research was used to explore the individual effect and interaction of diabetes and family history and other risk factors on hypertension. The individual effect of family history (OR = 4.103, 95%CI 2.660-6.330), diabetes (OR = 4.219, 95%CI 2.926-6.083), personal taste (OR = 1.256, 95%CI 1.091-1.593), drinking behavior (OR = 1.391, 95%CI 1.010-1.914) and smoking behavior (OR = 1.057, 95%CI 1.00-1.117) were significant (p < 0.05). But individual effect of sex, education, occupation, work/life pressure, environmental noise, sleeping time and sports habit were not significant (p > 0.05). The OR of interaction between FH and DM to hypertension was 16.537 (95%CI 10.070-21.157), between FH and drinking behavior was 4.0 (95%CI 2.461-6.502), FH and sport habit was 7.668 (95%CI 3.598-16.344), FH and personal taste was 6.521 (95%CI 3.858-11.024), FH and smoking behavior was 5.526 (95%CI 3.404-8.972), FH and work/life pressure was 4.087 (95%CI 2.144-7.788). The SI of FH and DM was 2.27, RERI was 8.68, AP was 52.48% and PAP was 55.86%. FH and DM, personal taste, smoking behavior had positive interaction on hypertension, but FH and sport habits, drinking behavior, work/life pressure had reverse interaction on hypertension. FH and diabetes were very important risk factors with significant effect for hypertension. FH and diabetes, personal taste, smoking behavior had positive interaction on hypertension, but FH and sport habits, drinking behavior, work/life pressure had reverse interaction on hypertension.
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http://dx.doi.org/10.1038/s41598-021-83589-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907071PMC
February 2021

Gas-phase amination of aromatic hydrocarbons by corona discharge-assisted nitrogen fixation.

Sci Rep 2021 Feb 2;11(1):2841. Epub 2021 Feb 2.

Department of Chemistry, Zhejiang University, Hangzhou, 310027, People's Republic of China.

This paper reports on the gas-phase amination reaction of aromatic hydrocarbons occurring under corona discharge conditions with N gas as the nitrogen source. The corona discharge device within an atmospheric pressure chemical ionization source was employed to achieve the plasma-assisted N fixation, and the coupled ion trap mass spectrometer (IT-MS) was used to detect positively charged product ions. In the model case, under APCI conditions, unusual product ions, [M + 16] and [M + 14], were observed. Based on the high resolution MS data and tandem mass spectrometric information, [M + 16] was confirmed to be protonated p-toluidine and [M + 14] was confirmed to be p-methylphenylnitrenium ion. According to the experimental results of the isotopic labelling and substituent effect, one feasible mechanism is proposed as follows. Firstly, N is activated by plasma caused via the corona discharge and then electrophilically attacks toluene, yielding the key intermediate, p-methylphenylnitrenium; secondly, the intermediate undergoes double-hydrogen transfer reaction to give rise to the final product ion, protonated p-toluidine. This study may provide a novel idea to explore new and green method for the synthesis of anilines.
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http://dx.doi.org/10.1038/s41598-021-82190-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854734PMC
February 2021

Discrimination of Aminobiphenyl Isomers in the Gas Phase and Investigation of Their Complex Conformations.

J Am Soc Mass Spectrom 2021 Mar 2;32(3):716-724. Epub 2021 Feb 2.

Zhejiang Provincial Key Laboratory of Advanced Mass Spectrometry and Molecular Analysis, Institute of Mass Spectrometry, School of Material Science and Chemical Engineering, Ningbo University, Ningbo, Zhejiang 315211, China.

The analysis of positional isomers is of great significance because their different chemical properties but similar structures make separation difficult. In this work, a simple method for simultaneously discriminating three positional isomers of 2-aminobiphenyl (2-ABP), 3-ABP, and 4-ABP was studied by ion mobility spectrometry (IMS) and quantum mechanical calculations at the molecular level. In the experiments, three ABP isomers were mixed with α-, β-, and γ-cyclodextrins (CD), and the IMS results show that the three ABP isomers were clearly recognized by the formed complex of [α-CD + ABP + H] via measuring their IMS, in which the different ion mobilities of 1.515, 1.544, 1.585 Vscom with the collision cross sections (CCS) of 307.3, 312.5, 320.8 Å were obtained for [α-CD + 2-ABP + H], [α-CD + 3-ABP + H], and [α-CD + 4-ABP + H], respectively. Collision induced dissociation analysis of the three [α-CD + ABP + H] isomer complexes were further studied, indicating that the same fragmentation process required different collisional energies, and the greater the CCS for the [α-CD + ABP + H] with looser structure and the smaller energy required. Besides, the favorable conformation and the CCS value of the different [CD + ABP + H] isomer complexes were measured via quantum mechanical calculations to detail their intermolecular interactions. It revealed that the intermolecular binding between 2-ABP and α-CD is different from that of 3- and 4-ABP, resulting in different molecular conformations and CCS, and the interaction modes of ABP with β-CD are similar to that with γ-CD, which are very consistent with the experimental observations. Finally, relative quantification of the method was performed, and satisfactory linearity with correlation coefficients () greater than 0.99 was obtained. This method for isomer discrimination and conformation analysis possesses the advantages of simplicity, sensitivity, cost-effectiveness, and as such it may be widely applied in chemistry and pharmaceutical sciences.
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http://dx.doi.org/10.1021/jasms.0c00426DOI Listing
March 2021

Point-of-care test system for detection of immunoglobulin-G and -M against nucleocapsid protein and spike glycoprotein of SARS-CoV-2.

Sens Actuators B Chem 2021 Mar 4;331:129415. Epub 2021 Jan 4.

Center for Advanced Measurement Science, National Institute of Metrology, Beijing, 100029, PR China.

The coronavirus disease 2019 (COVID-19) epidemic continues to ravage the world. In epidemic control, dealing with a large number of samples is a huge challenge. In this study, a point-of-care test (POCT) system was successfully developed and applied for rapid and accurate detection of immunoglobulin-G and -M against nucleocapsid protein (anti-N IgG/IgM) and receptor-binding domain in spike glycoprotein (anti-S-RBD IgG/IgM) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Any one of the IgG/IgM found in a sample was identified as positive. The POCT system contains colloidal gold-based lateral flow immunoassay test strips, homemade portable reader, and certified reference materials, which detected anti-N and anti-S-RBD IgG/IgM objectively in serum within 15 min. Receiver operating characteristic curve analysis was used to determine the optimal cutoff values, sensitivity, and specificity. It exhibited equal to or better performances than four approved commercial kits. Results of the system and chemiluminescence immunoassay kit detecting 108 suspicious samples had high consistency with kappa coefficient at 0.804 (P < 0.001). Besides, the levels and alterations of the IgG/IgM in an inpatient were primarily investigated by the POCT system. Those results suggested the POCT system possess the potential to contribute to rapid and accurate serological diagnosis and epidemiological survey of COVID-19.
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http://dx.doi.org/10.1016/j.snb.2020.129415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833039PMC
March 2021

Pro-inflammatory Mediators and Oxidative Stress: Therapeutic Markers for Recurrent Angina Pectoris after Coronary Artery Stenting in Elderly Patients.

Curr Vasc Pharmacol 2021 Jan 29. Epub 2021 Jan 29.

Department of Geriatrics, The Affiliated Huaian Hospital of Xuzhou Medical University, Huaian 223002. China.

Background: Pro-inflammatory mediators and oxidative stress are related to severity of angina pectoris in patients with coronary heart disease.

Objective: We evaluated the effects of pro-inflammatory mediators and oxidative stress on recurrent angina pectoris after coronary artery stenting in elderly patients.

Methods: We determined the expression levels of malondialdehyde (MDA), acrolein (ACR), tumour necrosis factor-α (TNF-α), toll-like receptor 4 (TLR4), superoxide dismutase 3 (SOD3), paraoxonase-1 (PON-1), stromal cell-derived factor-1α (SDF-1α) and endothelial progenitor cells (EPCs) in elderly patients with recurrent angina pectoris after coronary artery stenting.

Results: Levels of MDA, ACR, TNF-α and TLR4 were significantly increased (p<0.001), and levels of SOD3, PON-1, SDF-1α and EPCs were significantly decreased (p<0.001) in the elderly patients with recurrent angina pectoris after coronary artery stenting. MDA, ACR, TNF-α and TLR4 as markers of oxidative stress and pro-inflammatory mediators may have suppressed SOD3, PON-1, SDF-1α and EPCs as markers of anti-oxidative stress/anti-inflammatory responses. Oxidative stress and pro-inflammatory mediators were important factors involved in recurrent angina pectoris of elderly patients after coronary artery stenting.

Conclusion: Oxidative stress and pro-inflammatory mediators could be considered as potential non-invasive prognostic, predictive and therapeutic biomarkers for stable recurrent angina and recurrent unstable angina in the elderly patients after coronary artery stenting.
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http://dx.doi.org/10.2174/1570161119666210129142707DOI Listing
January 2021

Association between acne and smoking: systematic review and meta-analysis of observational studies.

Chin Med J (Engl) 2021 Jan 5;Publish Ahead of Print. Epub 2021 Jan 5.

Department of Dermatology, People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Key Laboratory of Dermatology Research (XJYS1707), Urumqi, Xinjiang 830001, China.

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http://dx.doi.org/10.1097/CM9.0000000000001286DOI Listing
January 2021

Effect of Kefir on Soybean Isoflavone Aglycone Content in Soymilk Kefir.

Front Nutr 2020 16;7:587665. Epub 2020 Dec 16.

College of Food Science, South China Agricultural University, Guangzhou, China.

Kefir is a traditional fermented milk originating in the Caucasus area and parts of Eastern Europe. In this study, the kefir culture, which is modified upon the addition of lactic acid bacteria (LAB) cells, specifically for soymilk kefir fermentation with the highest capacity of isoflavone biotransformation, was successfully produced, and the metagenomics composition of soymilk or milk fermented using these kefir cultures was investigated. The metagenome analysis showed that the microbiota of kefir in M-K (milk inoculated with kefir), SM-K (equal volumes of soymilk and milk inoculated with kefir), and S-K (pure milk inoculated with kefir) were related to the addition of soymilk or not. Furthermore, the HPLC chromatogram revealed that Guixia 2 (Guangzhou, China) may be a good source of soymilk kefir fermentation due to its high isoflavone aglycone content (90.23 ± 1.26 μg/g in daidzein, 68.20 ± 0.74 μg/g in genistein). Importantly, the starter culture created by adding 1.5 g probiotics (Biostime®, Guangzhou, China) to Chinese kefir showed a significant increase in the levels of isoflavone aglycones (72.07 ± 0.53 μg/g in isoflavone aglycones). These results provided insight into understanding the suitable soybean cultivar and starter cultures, which exhibit promising results of isoflavone biotransformation and flavor promotion during soymilk kefir fermentation.
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http://dx.doi.org/10.3389/fnut.2020.587665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772187PMC
December 2020

Highly accurate and sensitive diagnostic detection of SARS-CoV-2 by digital PCR.

Talanta 2021 Mar 27;224:121726. Epub 2020 Oct 27.

Center for Advanced Measurement Science, National Institute of Metrology, Beijing, 100013, China. Electronic address:

The outbreak of COVID-19 caused by a novel Coronavirus (termed SARS-CoV-2) has spread to over 210 countries around the world. Currently, reverse transcription quantitative qPCR (RT-qPCR) is used as the gold standard for diagnosis of SARS-CoV-2. However, the sensitivity of RT-qPCR assays of pharyngeal swab samples are reported to vary from 30% to 60%. More accurate and sensitive methods are urgently needed to support the quality assurance of the RT-qPCR or as an alternative diagnostic approach. A reverse transcription digital PCR (RT-dPCR) method was established and evaluated. To explore the feasibility of RT-dPCR in diagnostic of SARS-CoV-2, a total of 196 clinical pharyngeal swab samples from 103 suspected patients, 77 close contacts and 16 supposed convalescents were analyzed by RT-qPCR and then measured by the proposed RT-dPCR. For the 103 fever suspected patients, 19 (19/25) negative and 42 (42/49) equivocal tested by RT-qPCR were positive according to RT-dPCR. The sensitivity of SARS-CoV-2 detection was significantly improved from 28.2% by RT-qPCR to 87.4% by RT-dPCR. For 29 close contacts (confirmed by additional sample and clinical follow up), 16 (16/17) equivocal and 1 negative tested by RT-qPCR were positive according to RT-dPCR, which is implying that the RT-qPCR is missing a lot of asymptomatic patients. The overall sensitivity, specificity and diagnostic accuracy of RT-dPCR were 91%, 100% and 93%, respectively. RT-dPCR is highly accurate method and suitable for detection of pharyngeal swab samples from COVID-19 suspected patients and patients under isolation and observation who may not be exhibiting clinical symptoms.
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http://dx.doi.org/10.1016/j.talanta.2020.121726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588801PMC
March 2021