Publications by authors named "Meng Xu"

994 Publications

Tuberculosis recurrence over 7-year follow-up period in successfully treated patients in a routine programme setting in China: a prospective longitudinal study.

Int J Infect Dis 2021 Jul 28. Epub 2021 Jul 28.

International Union Against Tuberculosis and Lung Disease, Paris, France.

Objectives: To determine tuberculosis (TB) recurrence in previously successfully treated patients in routine program setting and baseline characteristics associated with TB recurrence.

Methods: A prospective longitudinal study in Jiangxi Province, China. Patients, ≥14 years old, were consecutively registered and were followed-up for 7-year to assess TB recurrence against patients' individual baseline data that was entered into a database at TB registration.

Results: There were 800 TB patients registered at baseline and 634 (79.2%) of them completed anti-TB treatments. Fifty nine (9.3%) died and 21 (3.3%) were lost to follow-up over the follow-up period. There were 96 patients with recurrent episodes (total incidence 15.2% or annual incidence 2,200/100,000). Of the recurrent cases, 53 (55.2%) happened within 2-year after completion of anti-TB treatments. After controlling confounding factors, risk of TB recurrence was significantly higher in age range 34-73 years (P<0.01) and current smokers (P<0.01).

Conclusions: Overall recurrence rate among previously treated TB patients was much higher compared to initial incidence in the same population (61-98/100,000) and settings with similar TB incidence. TB programs should consider closer monitoring for these patients for early detection of recurrence. Particular attention should be given to those between 34-73 years and those who use tobacco products.
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http://dx.doi.org/10.1016/j.ijid.2021.07.057DOI Listing
July 2021

Azoxystrobin increases the infection of spring viraemia of carp virus in fish.

Chemosphere 2021 Jul 9;285:131465. Epub 2021 Jul 9.

State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, 315211, China; Key Laboratory of Applied Marine Biotechnology of Ministry of Education, Meishan Campus, Ningbo University, Ningbo, 315832, China. Electronic address:

Azoxystrobin (AZ) has entered aquatic ecosystems and produced serious damages to fish associated with potentially increasing the susceptibility to pathogens. This study characterized the defense abilities of fish by exposed to AZ on challenging with the infection of spring viraemia of carp virus (SVCV). The results showed that SVCV replication increased significantly in EPC cells and zebrafish that were exposed to up to 50 μg/L of AZ at 3, 5, 7, and 14 d. Intracellular biochemical assays indicated that AZ at 5 and 50 μg/L inhibited the activation of Nrf2-ARE pathway including a decrease in Nrf2 expression, Nrf2 phosphorylation, HO-1 content, and three antioxidant activities. While no significant difference in ERK1/2 and JNK MAPKs in zebrafish was observed, P38 phosphorylation was significantly decreased at 7 and 14 d, and the changes in MAPKs were more evident in EPC cells previously exposed to AZ at 7 d. These results revealed that AZ initially induced low phosphorylation of MAPKs, triggering the attenuation of Nrf2 phosphorylation to weaken Nrf2 translocation into the nucleus in a longer exposure period (more than 5 d). The data in the cells and fish also showed that antioxidant activities were decreased to some extent at 5-7 d for the cells and 7-14 d for the fish. Furthermore, interferon-related factors were decreased in AZ-exposed zebrafish, explaining the reason that fish can't resist the virus infection. Overall, the present study provided a new adverse threat of AZ by amplifying the viral outbreak to endanger ecological safety in aquatic environment.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131465DOI Listing
July 2021

Cryo-EM structure of human Wntless in complex with Wnt3a.

Nat Commun 2021 07 27;12(1):4541. Epub 2021 Jul 27.

Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.

Wntless (WLS), an evolutionarily conserved multi-pass transmembrane protein, is essential for secretion of Wnt proteins. Wnt-triggered signaling pathways control many crucial life events, whereas aberrant Wnt signaling is tightly associated with many human diseases including cancers. Here, we report the cryo-EM structure of human WLS in complex with Wnt3a, the most widely studied Wnt, at 2.2 Å resolution. The transmembrane domain of WLS bears a GPCR fold, with a conserved core cavity and a lateral opening. Wnt3a interacts with WLS at multiple interfaces, with the lipid moiety on Wnt3a traversing a hydrophobic tunnel of WLS transmembrane domain and inserting into membrane. A β-hairpin of Wnt3a containing the conserved palmitoleoylation site interacts with WLS extensively, which is crucial for WLS-mediated Wnt secretion. The flexibility of the Wnt3a loop/hairpin regions involved in the multiple binding sites indicates induced fit might happen when Wnts are bound to different binding partners. Our findings provide important insights into the molecular mechanism of Wnt palmitoleoylation, secretion and signaling.
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http://dx.doi.org/10.1038/s41467-021-24731-3DOI Listing
July 2021

Quantitative Microbial Risk Assessment of and in Public Drinking Water in China.

Biomed Environ Sci 2021 Jun;34(6):493-498

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), Shanghai 200025, China;NHC Key Laboratory of Parasite and Vector Biology, Shanghai 200025, China;WHO Collaborating Centre for Tropical Diseases, Shanghai 200025, China;National Center for International Research on Tropical Diseases, Shanghai 200025, China;School of Global Health, Chinese Center for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

We aimed to assess the risks of and infections associated with drinking water for local residents, based on a quantitative microbial risk assessment, in three densely populated regions of China. In total, 45 source water samples and 45 treated water samples were collected from June to December 2014. Five -positive samples and 5 -positive samples were found. The annual probability of infection for individuals in Jintan (6.27 × 10 -2.05 × 10 for and 7.18 × 10 -2.32 × 10 for ), Ezhou (6.27 × 10 -1.10 × 10 for and 3.65 × 10 -1.20 × 10 for ), and Binyang (3.79 × 10 -1.25 × 10 for ) exceeded the tolerable risk of infection of 10 set by the United States Environmental Protection Agency. Moreover, the corresponding disease burdens of cryptosporidiosis and giardiasis, due to direct drinking and residual water in these regions, exceeded the threshold of 10 disability-adjusted life years per person per year set by the World Health Organization. These results provide insights into strategies to improve the safety of drinking water.
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http://dx.doi.org/10.3967/bes2021.068DOI Listing
June 2021

Targeting local lymphatics to ameliorate heterotopic ossification via FGFR3-BMPR1a pathway.

Nat Commun 2021 07 19;12(1):4391. Epub 2021 Jul 19.

Department of Wound Repair and Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China.

Acquired heterotopic ossification (HO) is the extraskeletal bone formation after trauma. Various mesenchymal progenitors are reported to participate in ectopic bone formation. Here we induce acquired HO in mice by Achilles tenotomy and observe that conditional knockout (cKO) of fibroblast growth factor receptor 3 (FGFR3) in Col2 cells promote acquired HO development. Lineage tracing studies reveal that Col2 cells adopt fate of lymphatic endothelial cells (LECs) instead of chondrocytes or osteoblasts during HO development. FGFR3 cKO in Prox1 LECs causes even more aggravated HO formation. We further demonstrate that FGFR3 deficiency in LECs leads to decreased local lymphatic formation in a BMPR1a-pSmad1/5-dependent manner, which exacerbates inflammatory levels in the repaired tendon. Local administration of FGF9 in Matrigel inhibits heterotopic bone formation, which is dependent on FGFR3 expression in LECs. Here we uncover Col2 lineage cells as an origin of lymphatic endothelium, which regulates local inflammatory microenvironment after trauma and thus influences HO development via FGFR3-BMPR1a pathway. Activation of FGFR3 in LECs may be a therapeutic strategy to inhibit acquired HO formation via increasing local lymphangiogenesis.
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http://dx.doi.org/10.1038/s41467-021-24643-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289847PMC
July 2021

High Expression of Tomm34 and Its Correlations With Clinicopathology in Oral Squamous Cell Carcinoma.

Pathol Oncol Res 2021 16;27:641042. Epub 2021 Apr 16.

Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China.

Tomm34, as a member of the outer mitochondrial membrane proteins, is evenly distributed between the cytoplasm and the outer mitochondrial membrane. It is up-regulated in a variety of tumors and correlates with poor prognosis. This study aimed to investigate expression of Tomm34 and its correlations with clinicopathology in oral squamous cell carcinoma (OSCC). Oncomine database and UALCAN database were utilized to predict the expression and prognosis values of Tomm34 in head and neck squamous cell carcinoma (HNSCC). By immunohistochemistry, a retrospective study was performed to verify the bioinformatics results to evaluate the Tomm34 expression and clinicopathological variables in both HPV-positive OSCC and HPV-negative OSCC. Immunohistochemistry of our cohort revealed that 48 cases fulfilled the Tomm34 high expression judgment criteria, and the overall positive rate was 60% (48/80), and 27 cases fulfilled the p16 expression judgment criteria (33.75%, 27/80). The high expression of Tomm34 was closely related with the TNM classification of OSCC ( < 0.01) and tumor size ( < 0.01) both in HPV-negative OSCC and HPV-positive OSCC, while related with lymph node metastasis ( = 0.001) in HPV-negative OSCC and drinking history ( = 0.044) in HPV-positive OSCC. In addition, the Kaplan-Meier curves indicated that higher level of Tomm34 was correlated with poorer overall survival (OS) and disease-free survival (DFS) in HPV-negative OSCC (OS, = 0.046; DFS, = 0.020) but not in HPV-positive OSCC (OS, = 0.824; DFS, = 0.782). In conclusion, Tomm34 is highly expressed in OSCC and may be a useful factor to provide prognostic information, especially in HPV-negative OSCC group.
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http://dx.doi.org/10.3389/pore.2021.641042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262227PMC
April 2021

Importance of brain alterations in spinal cord injury.

Sci Prog 2021 Jul-Sep;104(3):368504211031117

Beijing Key Laboratory for Biomaterials and Neural Regeneration, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.

Spinal cord injury (SCI) destroys the sensorimotor pathway and blocks the information flow between the peripheral nerve and the brain, resulting in autonomic function loss. Numerous studies have explored the effects of obstructed information flow on brain structure and function and proved the extensive plasticity of the brain after SCI. Great progress has also been achieved in therapeutic strategies for SCI to restore the "re-innervation" of the cerebral cortex to the limbs to some extent. Although no thorough research has been conducted, the changes of brain structure and function caused by "re-domination" have been reported. This article is a review of the recent research progress on local structure, functional changes, and circuit reorganization of the cerebral cortex after SCI. Alterations of structure and electrical activity characteristics of brain neurons, features of brain functional reorganization, and regulation of brain functions by reconfigured information flow were also explored. The integration of brain function is the basis for the human body to exercise complex/fine movements and is intricately and widely regulated by information flow. Hence, its changes after SCI and treatments should be considered.
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http://dx.doi.org/10.1177/00368504211031117DOI Listing
July 2021

Efficient propagation of the hierarchical equations of motion using the Tucker and hierarchical Tucker tensors.

J Chem Phys 2021 May;154(19):194104

Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Zhongguancun, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China; and Physical Science Laboratory, Huairou National Comprehensive Science Center, Beijing 101407, China.

We develop new methods to efficiently propagate the hierarchical equations of motion (HEOM) by using the Tucker and hierarchical Tucker (HT) tensors to represent the reduced density operator and auxiliary density operators. We first show that by employing the split operator method, the specific structure of the HEOM allows a simple propagation scheme using the Tucker tensor. When the number of effective modes in the HEOM increases and the Tucker representation becomes intractable, the split operator method is extended to the binary tree structure of the HT representation. It is found that to update the binary tree nodes related to a specific effective mode, we only need to propagate a short matrix product state constructed from these nodes. Numerical results show that by further employing the mode combination technique commonly used in the multi-configuration time-dependent Hartree approaches, the binary tree representation can be applied to study excitation energy transfer dynamics in a fairly large system including over 10 effective modes. The new methods may thus provide a promising tool in simulating quantum dynamics in condensed phases.
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http://dx.doi.org/10.1063/5.0050720DOI Listing
May 2021

Identification and characterization of a novel ELN mutation in congenital heart disease with pulmonary artery stenosis.

Sci Rep 2021 Jul 8;11(1):14154. Epub 2021 Jul 8.

Department of Cardiology, Shanghai Children's Hospital, Shanghai Jiaotong University, No. 355 Luding Road, Shanghai, 200062, China.

Congenital heart defects, one of the most common birth defects, affect approximately 1% of live birth globally and remain the leading cause of infant mortality in developed countries. Utilizing the pathogenicity score and inheritance mode from whole exome sequencing results, a heterozygous mutation (NM_001278939.1: c.1939G>T, p.Gly647Ter) in elastin (ELN) was identified among 6,440 variants in a female proband born with an atrial septal defect accompanied by pulmonary artery stenosis. Results of RT-PCR showed that the mutation (NM_001278939.1: c.1939G>T, p.Gly647Ter) did not affect the expression levels of ELN mRNA but increased protein level. The content of ELN truncate (functional component) was significantly lower in both the intracellular and extracellular compartments after mutation. These results indicate that the ELN mutation (NM_001278939.1: c.1939G>T, p.Gly647Ter) affected the protein truncate, which may be a functional component of ELN and play crucial roles for this pedigree. Here we report of an ELN heterozygous variant associated with congenital heart disease accompanied with pulmonary artery stenosis, which is less common. Based on our results, we speculate that this may be the main molecular mechanism underlying the mutation-led functional changes, and propose that the decrease of ELN protein level may cause this pedigree vascular abnormality, especially pulmonary artery stenosis, and reinforce the view that ELN insufficiency is the primary cause of these vascular lesions. This may be the main molecular mechanism underlying the mutation-led functional changes. Thus, systematic analysis not only enables us to better understand the etiology of this disease but also contributes to clinical and prenatal diagnosis.
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http://dx.doi.org/10.1038/s41598-021-93736-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266886PMC
July 2021

Severe right ventricular hypertrophy in hypertrophic cardiomyopathy: Serious symptoms, complex surgical procedures, and poor prognosis in Fuwai Hospital.

Anatol J Cardiol 2021 07;25(7):476-483

Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College; Beijing-China.

Objective: Severe right ventricular hypertrophy (SRVH) in hypertrophic cardiomyopathy (HCM) is rare. We studied the clinical characteristics and prognosis of 36 patients with HCM and SRVH in a Chinese cohort.

Methods: Patients with HCM and SRVH were enrolled between 2013 and 2017. The clinical characteristics, treatment therapies, and clinical outcomes of the 36 patients were retrospectively studied and compared with those of 128 patients without SRVH.

Results: Patients in the group with SRVH were younger than those in the group without SRVH (27.58±15.09 years vs 40.34±13.21 years, respectively; p<0.001). Patients with SRVH had more serious clinical symptoms and a higher New York Heart Association functional class than those without SRVH. Most patients in the group with SRVH exhibited diffuse RV hypertrophy, and 13 patients presented with biventricular outflow tract obstruction. Maximal left ventricular (LV) wall thickness (27.29±7.95 mm vs 24.33±5.85 mm, respectively; p=0.027) and LV outflow tract gradient (80.83±24.41 mm Hg vs 42.3±5.7 mm Hg, respectively; p=0.000) were significantly greater in patients with SRVH than in those without SRVH. A total of 30 patients in the group with SRVH underwent surgical correction. During a median follow-up period of 48 months, six patients with SRVH reached primary clinical endpoints (four sudden cardiac deaths, one heart failure-related death, and one heart transplantation), whereas only two deaths occurred in the patients without SRVH.

Conclusion: We conclude that patients with HCM and SRVH exhibit serious symptoms and have complex surgical requirements and poor clinical outcomes.
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http://dx.doi.org/10.5152/AnatolJCardiol.2021.98537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274897PMC
July 2021

LINC00174 Facilitates Cell Proliferation, Cell Migration and Tumor Growth of Osteosarcoma Regulating the TGF-β/SMAD Signaling Pathway and Upregulating SSH2 Expression.

Front Mol Biosci 2021 17;8:697773. Epub 2021 Jun 17.

Department of Orthopedics, The Second Hospital of Jilin University, Changchun, China.

Osteosarcoma (OS), a frequent malignant tumor which mainly occurs in the bone. The roles of long noncoding RNAs (lncRNAs) have been revealed in cancers, including OS. LncRNA long intergenic non-protein coding RNA (LINC00174) has been validated as an oncogene in several cancers. However, the role of LINC00174 in OS has not been explored. In our research, loss-of-function assays were conducted to explore the function of LINC00174 in OS cells. Then, we explored the downstream pathway of LINC00174 in OS cells. Bioinformatics, RNA pull-down and RIP experiments investigated the downstream mechanism of LINC00174 in OS cells. Finally, assays clarified the effect of LINC00174 on tumorigenesis. We found that LINC00174 was upregulated in OS tissues and cells. LINC00174 knockdown repressed OS cell growth. Mechanistically, LINC00174 knockdown suppressed the TGF-β/SMAD pathway. LINC00174 interacted with miR-378a-3p, and slingshot protein phosphatase 2 (SSH2) 3'UTR was targeted by miR-378a-3p in OS cells. Rescue assays showed that SSH2 upregulation or miR-378a-3p inhibition counteracted the inhibitory effect of LINC00174 depletion in OS cell growth. Additionally, LINC00174 depletion suppressed tumor growth in mice. In conclusion, LINC00174 promotes OS cellular malignancy and tumorigenesis the miR-378a-3p/SSH2 axis and the TGF-β/SMAD pathway, which might provide a novel insight for OS treatment.
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http://dx.doi.org/10.3389/fmolb.2021.697773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245779PMC
June 2021

Associated Factors of Oral Health-related Quality of Life in Chinese Adolescents Aged 12-15 Years.

Chin J Dent Res 2021 Jun;24(2):105-112

adolescents aged 12 to 15 years based on the 4th National Oral Health Survey and to explore its associated factors.

Methods: Students aged 12 to 15 years were recruited using to a multistage stratified random sampling method. All the subjects received oral examination and completed a questionnaire. Information relating to OHRQoL was collected through a Mandarin version of the child oral impacts on daily performances (Child-OIDP) questionnaire. The relationship between the Child-OIDP scores and independent variables was assessed using a Mann-Whitney U-test, Kruskal-Wallis test and a multivariate Poisson regression.

Results: A total of 89,582 subjects were included in the analysis, of whom 76.6% reported oral impacts in the last 6 months. Eating was the most affected daily performance. The results of the regression analysis showed that factors associated with adolescents' OHRQoL included sex, location of residence, region, only child status, parents' level of education, frequency of sugar consumption, self-perception of general/oral health, dental appointments in the past 12 months, oral health knowledge status, age, decayed, missing and filled teeth (DMFT) index and number of teeth with gingival bleeding.

Conclusion: Oral impacts were common among Chinese adolescents, although most were not so severe. Eating was the most commonly affected performance. Sex, location of residence, region, only child status, parents' level of education, frequency of sugar consumption, selfperception of general/oral health status, dental appointments in the previous 12 months, oral health knowledge status, age, DMFT index and number of teeth with gingival bleeding were found to be associated with OHRQoL.
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http://dx.doi.org/10.3290/j.cjdr.b1530497DOI Listing
June 2021

[Soil bacterial community composition and functional potentials along the vertical vegetation transect on Mount Segrila, Tibet, China].

Ying Yong Sheng Tai Xue Bao 2021 Jun;32(6):2147-2157

College of Agriculture, Guizhou University, Guiyang 550025, China.

Information on the spatial distribution of soil microbial communities on the Tibetan Pla-teau is critical for in-depth understanding the important roles of microbes in typical alpine ecosystems. In this study, 16S rDNA Illumina Miseq sequencing was used to analyze the variations in bacterial community composition and functional potentials in soils sampled from four elevations on Mount Segrila, Tibet, and the driving environmental factors. Results showed that richness and Shannon diversity index of soil bacteria significantly decreased with increasing altitude. The relative abundances of Acidobacteria, Chloroflexi, Gemmatimonadetes, and Nitrospirae significantly increased, whereas that of Proteobacteria, Actinobacteria and Bacteroidetes significantly decreased with increasing altitude. In KEGG pathway (level Ⅱ), the relative abundance of genes related to membrane transport and the metabolism of amino acids, lipids, terpenoids and polyketones was significantly lower at high elevations. In contrast, genes related to carbohydrates metabolism, signal transduction, replication and repair and enzyme family were more abundant at high altitudes. Soil bacterial community composition and predicted functions were significantly affected by vegetation types and soil properties, with soil pH being the key driver. There were significant correlations between the abundances of predicted functions and bacterial taxa, such as Acitnobacteria, Bacteroidetes, and Fibrobacteres. The dissimilarity in the composition of KEGG pathway genes along the elevational gradient (β-diversity) showed a significantly positive correlation with the dissimilarity in bacterial community structure, indicating that there was a strong relationship between microbial community composition and potential functionality.
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http://dx.doi.org/10.13287/j.1001-9332.202106.035DOI Listing
June 2021

Molecular Cloning, Transcriptional Profiling, Subcellular Localization, and miRNA-Binding Site Analysis of Six Genes in Poplar.

Plants (Basel) 2021 Jun 30;10(7). Epub 2021 Jun 30.

Key Laboratory of Forest Genetics and Biotechnology of Ministry of Education, Co-Innovation Center for Sustainable Forestry in Southern China, Nanjing Forestry University, Nanjing 210037, China.

The SCL9 subfamily is a key member of the GRAS family that regulates plant development and stress responses. Nevertheless, the functional role of these genes in the growth and development of poplar still unclear. Here, we reported the six genes, which were found to be differentially expressed during poplar adventitious root formation. The full-length sequences of genes of 'Nanlin895' poplar ( × ) were cloned by the RACE technique All genes lacked introns. RT-qPCR revealed that genes displayed a dynamic expression pattern in the adventitious root of poplar, according to RT-qPCR data. A series of comprehensive genes characteristics analysis were carried out for six genes by bioinformation. Meanwhile, transient expression analysis of the protoplasts showed that all the PeSCL9 proteins were localized in the nucleus. In addition, the degradome and sRNA of 'Nanlin895' poplar in combination were used to predict miRNAs that regulate . It was found that miR396a and miR396c may affect expression via cleavage, which was further verified by a transient expression experiment in protoplasts. Overall, the development of poplar adventitious root and other tissues was closely related to these six genes, and they serve as a starting point for further research into the mechanisms regulating poplar growth and development.
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http://dx.doi.org/10.3390/plants10071338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309000PMC
June 2021

Quantification and molecular imaging of fatty acid isomers from complex biological samples by mass spectrometry.

Chem Sci 2021 May 4;12(23):8115-8122. Epub 2021 May 4.

School of Pharmacy, University of Wisconsin-Madison Madison WI 53705 USA

Elucidating the isomeric structure of free fatty acids (FAs) in biological samples is essential to comprehend their biological functions in various physiological and pathological processes. Herein, we report a novel approach of using peracetic acid (PAA) induced epoxidation coupled with mass spectrometry (MS) for localization of the C[double bond, length as m-dash]C bond in unsaturated FAs, which enables both quantification and spatial visualization of FA isomers from biological samples. Abundant diagnostic fragment ions indicative of the C[double bond, length as m-dash]C positions were produced upon fragmentation of the FA epoxides derived from either in-solution or on-tissue PAA epoxidation of free FAs. The performance of the proposed approach was evaluated by analysis of FAs in human cell lines as well as mapping the FA isomers from cancer tissue samples with MALDI-TOF/TOF-MS. Merits of the newly developed method include high sensitivity, simplicity, high reaction efficiency, and capability of spatial characterization of FA isomers in tissue samples.
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http://dx.doi.org/10.1039/d1sc01614hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208125PMC
May 2021

Effect of acetabular morphological parameters applied in proximal femoral varus osteotomy on the treatment of developmental dysplasia of the hip in children.

Transl Pediatr 2021 May;10(5):1361-1368

Department of Pediatric Surgery, Linyi Central Hospital, Linyi, China.

Background: The study was carried out based on the background that though proximal femoral varus osteotomy is one of the most effective methods in treating developmental dysplasia of the hip (DDH), its surgical efficiency and effect need to be improved.

Methods: The neck shaft angle and acetabular morphological parameters were measured before and after operation and during clinical follow-up. The Severin criteria and McKay criteria were both adopted to score the measurements. The distance from the center of the femoral head to the medial cutting bone (expressed as C value) and the shortened lengths of the proximal femur (expressed as Δ S) calculated by formula and obtained by actual measurement were compared.

Results: The neck shaft angle and acetabular morphological parameters after operation and during clinical follow-up were significantly lower than those before operation (P<0.05). The proportion of children with McKay scores of I, II, III, and IV after operation was 50.00%, 41.67%, 8.33%, and 0.00%, respectively; while the proportion of children with Severin scores of I, II, III, and IV was 55.00%, 38.33%, 6.67%, and 0.00%, respectively. There were no significant differences in the C value and Δ S obtained after formula calculation and actual measurement (P>0.05).

Conclusions: The acetabular morphological parameters applied in proximal femoral varus osteotomy are of great value for the treatment of DDH in children.
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http://dx.doi.org/10.21037/tp-21-200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193007PMC
May 2021

An L0 regularization method for imaging genetics and whole genome association analysis on Alzheimer's disease.

IEEE J Biomed Health Inform 2021 Jun 28;PP. Epub 2021 Jun 28.

Although the neuroimaging measures build a bridge between genetic variants and disease phenotype, an assessment of single nucleotide variants changes in brain structure and their clinically influence on the progression of Alzheimers disease remain largely preliminary. Note that each variant has very weak correlation signal to neuroimaging measures or Alzheimers disease phenotype. Therefore, traditional sparse regression-based image genetics approaches confront with unresolvable features, relative high regression error or inapplicability of high-dimensional data. Adopting an L0 regularization method, we significantly elevate the regression accuracy of imaging genetics compared with group-sparse multitask regression method. With further analysis on the simulation results, we conclude that multiple regression tasks model may be unsuitable for image genetics. In addition, we carried out a whole genome association analysis between genetic variants (about 388 million loci) and phenotype (cognition normal, mild cognitive impairment and Alzheimer's disease) with using the L0 regularization method. After annotating the effect of all variants by Ensembl Variant Effect Predictor (VEP), our method located 33 missense variants which can explain 40.1% phenotypevariance. Then, we mapped each missense variant to the nearest gene and carried out pathway enrichment analysis. The Notch signaling pathway and Apoptosis pathway have been reported to be related to the formation of Alzheimer's disease.
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http://dx.doi.org/10.1109/JBHI.2021.3093027DOI Listing
June 2021

Roxadustat treatment for anemia in peritoneal dialysis patients: A randomized controlled trial.

J Formos Med Assoc 2021 Jun 21. Epub 2021 Jun 21.

Department of Nephrology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, China; Department of Nephrology, Institute of Nephrology, 2nd Affiliated Hospital of Hainan Medical University, Haikou, China. Electronic address:

Background/purpose: Roxadustat, a first-in-class hypoxia-inducible factor prolyl hydroxylase inhibitor, promotes erythropoiesis and regulates iron metabolism. This study investigated the efficacy and safety of roxadustat in Chinese patients with anemia on peritoneal dialysis (PD).

Methods: One hundred and twenty-nine patients were randomized and treated with roxadustat (n = 86) or erythropoiesis-stimulating agents (ESAs) (n = 43) for 24 weeks. The primary end points were the mean hemoglobin (Hb) level at week 24, the change in average Hb levels from baseline to week 24, and the cumulative response rate throughout the treatment period. The secondary end points included changes in hepcidin and iron indices and serum lipid levels. Subgroup analysis examined the effect of inflammatory status on the efficacy of Hb. Safety was assessed as the occurrence of emergent adverse events after treatment.

Results: The mean average Hb levels at week 24 and average change in Hb levels from baseline to week 24 were 11.5 g/dL and 2.5 g/dL in the roxadustat group and 11.2 g/dL and 2.2 g/dL in the ESAs group, respectively. The cumulative response rate was 96% in the roxadustat group and 92% in the ESAs group at week 24. Roxadustat decreased hepcidin levels and increased total iron-binding capacity. The decreases in total cholesterol and low-density lipoprotein cholesterol were greater with roxadustat than with ESAs. Roxadustat-induced Hb increases were independent of baseline C-reactive protein levels. Common adverse events included hyperkalemia, hypertension, and insomnia.

Conclusion: Roxadustat effectively corrected and maintained target Hb levels in Chinese PD patients. This trial was registered in the Chinese Clinical Trial Register (ChiCTR2000035054).
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http://dx.doi.org/10.1016/j.jfma.2021.06.004DOI Listing
June 2021

Clinico-pathological classification of rheumatic mitral valve damage and surgical strategy.

Authors:
Tiange Luo Xu Meng

J Thorac Dis 2021 May;13(5):2933-2941

Cardiac Valve Centre, Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University-Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.

Background: There is a lack of established pathological indications for rheumatic valve repair. Therefore, we summarized the pathological classifications of rheumatic heart diseases and their correlations with the surgical strategies.

Methods: This observational study enrolled patients with rheumatic heart diseases who underwent mitral valve repair (MVP) or replacement at our centre between January 2017 and January 2019. Mitral leaflet, mitral commissural, and sub-valvular apparatus were classified into three grades from mild to severe, according to their degree of pathological damage. Based on certain principles and the grade of mitral leaflet, mitral commissural, and sub-valvular apparatus damage, three pathological types were identified (types I to III), based on which all patients were classified. The features of each pathological type were summarised. Differences between the three pathological types were analysed using chi-square test of tendency. These data were used to propose a clinico-pathological classification of rheumatic mitral valve damage in Chinese patients.

Results: Of 398 patients, 284 (70%) underwent MVP for rheumatic mitral valve diseases. There were 58 type I (15%) patients in the study, all of whom underwent repair (repair rate, 100%). Preoperative moderate-to-severe regurgitation with mild pathological lesions was observed in 64% of these patients. In 260 type II (65%) patients, the repair rate was 76% (197/260); preoperative moderate-to-severe stenosis was observed in 88% of these patients. In 80 type III (20%) patients, the repair rate was 36% (29/80); the preoperative rates of extremely severe stenosis and moderate-to-severe regurgitation in these patients were 50% and 40%, respectively. Several preoperative parameters show the change in trend with the increase in the pathological classification severity.

Conclusions: Our clinico-pathological classification of rheumatic mitral valve damage is applicable to MVP. Considering that the classification principles are based on the possibility of mitral repair, it provides a phased and achievable target ratio for MVP and a principle of screening patients who should undergo rheumatic MVP.
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http://dx.doi.org/10.21037/jtd-20-3456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182522PMC
May 2021

Modified cotton fabric based on thiolene click reaction and its oil/water separation application.

Environ Technol 2021 Jun 23:1-10. Epub 2021 Jun 23.

College of Life Science, College of Textile and Garment, Shaoxing University, Shaoxing, People's Republic of China.

A cotton fabric with special wettability was prepared in two simple steps. The surface of the fabric was grafted with silicon-oxygen group using 3-(methacryloyloxy) propyl trimethoxysilane (MSPMA) as the reagent, and then (3-mercaptopropyl)triethoxysilane (MPTES) was used to react with the grafted fabric under ultraviolet light according to the principle of thiolene reaction. Meanwhile, the modified cotton fabrics with various pore sizes were obtained via modifying the cotton fabric with different pore size under the same experimental conditions. The as-prepared fabric had a better hydrophobic and lipophilic effect, whose water contact angle could be up to 146.7° and the separation efficiency for different kinds of oil/water mixtures was better than 94%. In addition, the pore sizes of cotton fabrics had a great effect on the rate of oil/water separation, which increased with the increase of the pore size.
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http://dx.doi.org/10.1080/09593330.2021.1944324DOI Listing
June 2021

Ulinastatin plus biapenem for severe pneumonia in the elderly and its influence on pulmonary function and inflammatory cytokines.

Am J Transl Res 2021 15;13(5):5027-5034. Epub 2021 May 15.

Intensive Care Unit, The First Hospital of Kunming Kunming 650224, Yunnan Province, China.

To estimate the efficacy of ulinastatin (UTI) plus biapenem (BIPM) in the treatment of severe pneumonia in the elderly and its influence on pulmonary function (PF) and inflammatory cytokines.

Methods: We included 97 elderly patients with severe pneumonia in the present study. Patients in control group (n=47) were given BIPM, and those in research group (n=50) were treated with BIPM plus UTI. The clinical efficacy, adverse reactions, arterial blood gas (ABG) indices, PF and inflammatory cytokines were recorded.

Results: Patients in the research group had earlier fever clearance, inflammation absorption and cough disappearance than those in control group, as well as better clinical efficacy. In addition, no significant differences were found in the incidence of adverse reactions between the two groups during treatment. Monitoring changes in ABG indices, PF, and inflammatory cytokines revealed increased levels of PaO, pH, FEV1, FVC, FEV1/FVC after treatment, but levels of PaCO, IL-1β, IL-6, TNF-α, and hs-CRP decreased compared to before treatment. Levels of indices that increased after treatment in the research group were higher than those in the control group, whereas the levels of other indices that decreased after treatment were lower.

Conclusion: The combination of UTI and BIPM shortens the time of symptom disappearance, enhances PF, and inhibits inflammation, achieving higher efficacy in the treatment of severe pneumonia in the elderly.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205704PMC
May 2021

Vpr counteracts the restriction of LAPTM5 to promote HIV-1 infection in macrophages.

Nat Commun 2021 06 17;12(1):3691. Epub 2021 Jun 17.

Department of Laboratory Medicine, Key Laboratory of AIDS Immunology of Ministry of Health, The First Affiliated Hospital, China Medical University, Shenyang, China.

The HIV-1 accessory proteins Vif, Vpu, and Nef can promote infection by overcoming the inhibitory effects of the host cell restriction factors APOBEC3G, Tetherin, and SERINC5, respectively. However, how the HIV-1 accessory protein Vpr enhances infection in macrophages but not in CD4 T cells remains elusive. Here, we report that Vpr counteracts lysosomal-associated transmembrane protein 5 (LAPTM5), a potent inhibitor of HIV-1 particle infectivity, to enhance HIV-1 infection in macrophages. LAPTM5 transports HIV-1 envelope glycoproteins to lysosomes for degradation, thereby inhibiting virion infectivity. Vpr counteracts the restrictive effects of LAPTM5 by triggering its degradation via DCAF1. In the absence of Vpr, the silencing of LAPTM5 precisely phenocopied the effect of Vpr on HIV-1 infection. In contrast, Vpr did not enhance HIV-1 infection in the absence of LAPTM5. Moreover, LAPTM5 was highly expressed in macrophages but not in CD4 T lymphocytes. Re-expressing LAPTM5 reconstituted the Vpr-dependent promotion of HIV-1 infection in primary CD4 T cells, as observed in macrophages. Herein, we demonstrate the molecular mechanism used by Vpr to overcome LAPTM5 restriction in macrophages, providing a potential strategy for anti-HIV/AIDS therapeutics.
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http://dx.doi.org/10.1038/s41467-021-24087-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211709PMC
June 2021

Efficacy and Treatment Strategies in Advanced Cancers with Liver Metastasis Receiving Atezolizumab Therapy.

Cancer Manag Res 2021 8;13:4541-4551. Epub 2021 Jun 8.

Department of Surgery, Guangdong Women and Children Hospital, Guangzhou, People's Republic of China.

Background: Atezolizumab has been used to treat patients with liver metastasis (LM). However, whether atezolizumab is superior to standard of care therapy in an all-comer or selective population with LM is still uncertain.

Methods: A pooled analysis based on 10 randomized controlled trials was conducted to evaluate the clinical benefit of atezolizumab versus standard therapy in patients stratified by liver metastatic status, followed by biomarker-based individual analyses of the non-small cell lung cancer (NSCLC) cohort (OAK and POPLAR studies) and urothelial cancer cohort (IMvigor210 study).

Results: The pooled analysis demonstrated an overall survival (OS) improvement using atezolizumab treatment versus standard therapy across cancer types and treatment lines regardless of liver metastatic status. However, the efficacy of atezolizumab in patients with LM from the second-line setting was limited, based on the individual analysis of NSCLC cohorts ( = 0.053). PD-L1 strong expression emerged as a predominant biomarker ( = 0.015) to screen atezolizumab-advantageous patients with LM. Notably, the combination of PD-L1 and LM improved the predictive power for atezolizumab therapy in both NSCLC and urothelial cancer cohorts. Exploratory translational analysis revealed that strong expression of PD-L1 might have reversed the non-inflamed immune phenotype of liver metastasis, thus sensitizing these patients to immunotherapy.

Conclusion: Our study demonstrated a preferable efficacy of atezolizumab in patients with LM as first-line therapy over standard of care therapy, while sensitive patients should be selected in second-line settings. PD-L1 was demonstrated as the most effective biomarker for screening atezolizumab-advantageous patients with LM.
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http://dx.doi.org/10.2147/CMAR.S310331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197666PMC
June 2021

Detection of Posttranslational Modification Autoantibodies Using Peptide Microarray.

Methods Mol Biol 2021 ;2344:99-106

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences-Beijing (PHOENIX Center), Beijing Institute of Lifeomics, Beijing, China.

Autoantibodies are humoral antibodies against self-proteins and play vital roles in maintaining the homeostasis. Autoantibodies can also target posttranslational modifications (PTMs) of proteins and the identification of new PTM autoantibodies is important to identify biomarkers for the early diagnosis of cancer and autoimmune diseases. In this chapter, we describe a method to detect PTM autoantibodies using citrullinated peptide microarray as an example. This method can be used to screen serum autoantibodies for different human diseases.
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http://dx.doi.org/10.1007/978-1-0716-1562-1_7DOI Listing
January 2021

Fluorescence Switchable Block Copolymer Particles with Doubly Alternate-Layered Nanoparticle Arrays.

Small 2021 Jul 10;17(28):e2101222. Epub 2021 Jun 10.

Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.

The precise self-assembly of block copolymers (BCPs) and inorganic nanoparticles (NPs) under 3D confinement offers microparticles with programmable nanostructures and functionalities. Here, fluorescence-switchable hybrid microspheres are developed by forming doubly alternating arrays of Au NPs and CdSe/ZnS quantum dots (QDs) within polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP) BCP domains. These doubly alternating arrays afford controlled nonradiative energy transfer (NRET) between the QDs and Au NPs that is dependent on the layer-to-layer distance. Solvent-selective swelling of the hybrid particles tunes the distance between layers, modulating their NRET behavior and affording switchable fluorescence. The particle fluorescence is "OFF" in water through strong NRET from the QDs to Au NPs, but is "ON" in alcohols due to the increased distance between the Au NP and QD arrays in the swollen P4VP domains. The experimentally observed NRET intensity as a function of interparticle distance shows larger quenching efficiencies than those theoretically predicted due to the enhanced quenching within a 3D-confined system. Finally, the robust and reversible fluorescence switching of the hybrid particles in different solvents is demonstrated, highlighting their potentials for bioimaging, sensing, and diagnostic applications.
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http://dx.doi.org/10.1002/smll.202101222DOI Listing
July 2021

CHD4 variants are associated with childhood idiopathic epilepsy with sinus arrhythmia.

CNS Neurosci Ther 2021 Jun 9. Epub 2021 Jun 9.

Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China.

Aims: CHD4 gene, encoding chromodomain helicase DNA-binding protein 4, is a vital gene for fetal development. In this study, we aimed to explore the association between CHD4 variants and idiopathic epilepsy.

Methods: Trios-based whole-exome sequencing was performed in a cohort of 482 patients with childhood idiopathic epilepsy. The Clinical Validity Framework of ClinGen and an evaluating method from five clinical-genetic aspects were used to determine the association between CHD4 variants and epilepsy.

Results: Four novel heterozygous missense mutations in CHD4, including two de novo mutations (c.1597A>G/p.K533E and c.4936G>A/p.E1646K) and two inherited mutations with co-segregation (c.856C>G/p.P286A and c.4977C>G/p.D1659E), were identified in four unrelated families with eight individuals affected. Seven affected individuals had sinus arrhythmia. From the molecular sub-regional point of view, the missense mutations located in the central regions from SNF2-like region to DUF1087 domain were associated with multisystem developmental disorders, while idiopathic epilepsy-related mutations were outside this region. Strong evidence from ClinGen Clinical Validity Framework and evidences from four of the five clinical-genetic aspects suggested an association between CHD4 variants and epilepsy.

Conclusions: CHD4 was potentially a candidate pathogenic gene of childhood idiopathic epilepsy with arrhythmia. The molecular sub-regional effect of CHD4 mutations helped explaining the mechanisms underlying phenotypic variations.
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http://dx.doi.org/10.1111/cns.13692DOI Listing
June 2021

LncRNA BCRT1 facilitates osteosarcoma progression via regulating miR-1303/FGF7 axis.

Aging (Albany NY) 2021 06 8;13(11):15501-15510. Epub 2021 Jun 8.

Department of Orthopedics, The First Medical Center of General Hospital of PLA, Beijing 100853, China.

Growing studies noted that lncRNA was closely related with the initiation and progression of tumors. However, the role of BCRT1 in the progression of osteosarcoma remains unknown. We noted that BCRT1 is significantly upregulated in osteosarcoma specimens and cells. Elevated expression of BCRT1 promotes cell growth and cell cycle in osteosarcoma cell. Moreover, BCRT1 induces EMT and secretion of inflammatory mediators in osteosarcoma cell. We illustrated that elevated expression of BCRT1 decreases miR-1303 expression in MG-63 cell. The expression of miR-1303 is lower in osteosarcoma specimens than in non-tumor specimens. There is an inverse interrelation between miR-1303 levels and BCRT1 levels in osteosarcoma specimens. Furthermore, we identified FGF7 is one direct target gene of miR-1303 in osteosarcoma cell. Ectopic expression of miR-1303 suppresses FGF7 expression and elevated expression of BCRT1 enhanced FGF7 expression in MG-63 cell. Finally, we illustrated that BCRT1 induces osteosarcoma cell cycle and proliferation and promotes EMT progression and inflammatory mediators secretion via modulating FGF7 expression. Our study suggested that BCRT1 acts as one oncogene in osteosarcoma progression.
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http://dx.doi.org/10.18632/aging.203106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221344PMC
June 2021

Goethite/biochar-activated peroxymonosulfate enhances tetracycline degradation: Inherent roles of radical and non-radical processes.

Sci Total Environ 2021 Aug 14;783:147102. Epub 2021 Apr 14.

School of Water Conservancy and Environment, University of Jinan, Jinan 250022, PR China.

While biochar supported iron materials have been widely studied in advanced oxidation processes (AOPs), little is known about the effect and mechanism of goethite/biochar in sulfate radical (SO) based AOPs. Herein, a novel goethite/biochar composite was applied as peroxymonosulfate (PMS) activator for tetracycline (TC) degradation in the water. The superior catalytic efficiency of goethite/biochar was achieved through radical (OH and SO) and non-radical (O) processes according to the radicals quenching experiments and electron paramagnetic resonance analysis. Carbonyl group and Fe species were the main active sites on the surface of goethite/biochar, which was demonstrated by combining Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and reaction kinetic experiments. Furthermore, nine main by-products of TC degradation were detected by liquid chromatography-mass spectrometry and the reasonable degradation pathway was proposed according to the molecular structure analysis. Overall, the goethite/biochar materials could be applied to activate PMS for TC degradation, and this study will benefit the application of iron/biochar materials in practical water treatment.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147102DOI Listing
August 2021

Positively charged collective oscillations induce efficient Aβ1-42 fibril degradation in the presence of novel [email protected] core/shell nanorods.

Chem Commun (Camb) 2021 Jun;57(52):6384-6387

Beijing Key Laboratory of Construction Tailorable Advanced Functional Materials and Green Applications, Experimental Center of Advanced Materials, School of Materials Science and Engineering, Beijing Institute of Technology, China. and Key Laboratory of Medical Molecular Science and Pharmaceutical Engineering, MIIT, Institute for Engineering Medicine, BIT, Beijing 100081, China.

We synthesized [email protected] core/shell nanorods (NRs) that have synergistic surface plasmon resonance (SPR) effects using a new cation exchange process in ethylene glycol (EG) phase. The dual effect - NIR photothermal and surface positive charge plasmon - of [email protected] NRs, promote the capability to degrade Aβ1-42 fibrils into amorphous protein.
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http://dx.doi.org/10.1039/d1cc01470fDOI Listing
June 2021
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