Publications by authors named "Huan Wu"

211 Publications

Trends in Comorbidities and Postoperative Complications of Geriatric Hip Fracture Patients from 2000 to 2019: Results from a Hip Fracture Cohort in a Tertiary Hospital.

Orthop Surg 2021 Aug 25. Epub 2021 Aug 25.

Department of Orthopedics, Chinese PLA General Hospital, Beijing, China.

Objective: To describe the secular trends in comorbidities and postoperative complications of geriatric hip fracture patients from the Chinese People's Liberation Army General Hospital Hip Fracture Cohort between 2000 and 2019.

Methods: We included 2,805 hip fracture patients aged 65 years or older and received surgical treatment from 25 January 2000 to 19 December 2019. Demographic characteristics, comorbidities, postoperative complications, length of hospital stay, and the time to surgery were extracted and examined in each 5-year period based on the admission year, namely 2000-2004, 2005-2009, 2010-2014, and 2015-2019. Categorical data were analyzed by chi-squared or Fisher's exact test, with ordinal data by row mean scores difference test and continuous data by one-way analysis of variance. Trends in comorbidities and postoperative complications were examined by the Cochran-Armitage trend test.

Results: The average age of the included population was 79.1 ± 7.3 years (mean ± standard deviation), and 69.1% were female. From 2000 to 2019, the proportion of females increased from 59.8% to 73.0% (P for trend <0.05). Hypertension (51.8%), type 2 diabetes (23.6%), coronary heart disease (20.9%), stroke (18.7%), and arrhythmia (11.2%) were the most prevalent five comorbidities. The proportion of hypertension was 27.0%, 45.4%, 53.0%, and 57.2% in each 5-year period with an increasing trend (P for trend <0.05). The proportion of type 2 diabetes was 9.8%, 22.8%, 23.5%, and 26.0% in each 5-year period (P for trend <0.05). Similar increasing trends were found in myocardial infarction, arrhythmia, and tumor. On the contrary, the proportion of patients with major postoperative complications decreased from 2000 to 2019, with 23.0%, 14.6%, 6.5%, and 5.6% in each 5-year period (P for trend <0.05). For each specific postoperative complication, i.e. pneumonia, cardiovascular event, respiratory failure, and in-hospital death, similar decreasing trends were found (all P for trend <0.05).

Conclusion: This descriptive analysis sheds light on the fact that the health status of the hip fracture population tends to shift gradually. Improving concepts and practices of clinical interventions may help reduce postoperative complications, whereas challenges in the management of comorbidities increase.
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http://dx.doi.org/10.1111/os.13142DOI Listing
August 2021

Case Report: Novel Biallelic Mutations in Cause Primary Ciliary Dyskinesia and Male Infertility in a Chinese Family.

Front Genet 2021 30;12:715339. Epub 2021 Jul 30.

Department of Obstetrics and Gynecology, Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Primary ciliary dyskinesia (PCD) is a clinically and genetically heterogeneous ciliopathy affecting the cilia and sperm flagella. Mutations in genes related to the structural and functional defects of respiratory ciliary axoneme have been reported to be the predominant cause of this symptom; however, evidence regarding male infertility and genotype-phenotype associations between some of these genes and flagellar axoneme remains unclear. Here, we reported a male patient from a non-consanguineous Chinese family who exhibited left/right body asymmetry and oligoasthenoterazoospermia factor infertility. Novel compound heterozygous mutations in (NM:018076: c.2095C>T: p. Gln699; c.1679C>T: p. Ala560Val) were identified in this patient, and his parents were a heterozygous carrier for the mutations. Morphological and ultrastructural analysis of the spermatozoa from the man showed aberrant sperm flagella with axonemal disorganization and outer dynein arm (ODA) loss. In addition, immunofluorescence analysis of the spermatozoa from the proband and a control man revealed a significant lower expression of ARMC4 protein due to pathogenic mutations. Therefore, our findings help to expand the spectrum of pathogenic mutations and linked biallelic mutations to male infertility for the first time.
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http://dx.doi.org/10.3389/fgene.2021.715339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362595PMC
July 2021

Polystyrene microplastics disrupt the blood-testis barrier integrity through ROS-Mediated imbalance of mTORC1 and mTORC2.

Environ Pollut 2021 Aug 3;289:117904. Epub 2021 Aug 3.

Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, PR China; Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing Key Laboratory of Pediatrics, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, PR China.

It has been found that polystyrene microplastics (PS-MPs) exposure leads to decreased sperm quality and quantity, and we aim to explore the underlying mechanisms. Therefore, we gave 20 mg/kg body weight (bw) and 40 mg/kg bw 4 μm and 10 μm PS-MPs to male Balb/c mice by gavage. RNA sequencing of testes was performed. After PS-MPs exposure, blood-testis barrier (BTB) integrity was impaired. Since cytoskeleton was closely related to BTB integrity maintenance, and cytoskeleton disorganization could be induced by PS-MPs exposure in the testis, which resulted in the truncation of actin filaments and disruption of BTB integrity. Such processes were attributed to the differential expression of Arp3 and Eps8 (two of the most important actin-binding proteins). According to the transcriptome sequencing results, we examined the oxidative stress level in the testes and Sertoli cells. We found that PS-MPs exposure induced increased reactive oxygen species (ROS) level, which destroyed the balance between mTORC1 and mTORC2 (the mTORC1 activity was increased, while the mTORC2 activity was decreased). In conclusion, PS-MPs induced the imbalance of mTORC1 and mTORC2 via the ROS burst, and altered the expression profile of actin-binding proteins, resulting in F-actin disorganization and reduced expression of junctional proteins in the BTB. Eventually PS-MPs led to BTB integrity disruption and spermatogenesis dysfunction.
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http://dx.doi.org/10.1016/j.envpol.2021.117904DOI Listing
August 2021

Wnt5a Regulates Junctional Function of Sertoli cells Through PCP-mediated Effects on mTORC1 and mTORC2.

Endocrinology 2021 Oct;162(10)

Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, PR China.

The blood-testis barrier (BTB) and apical ectoplasmic specialization (ES), which are synchronized through the crosstalk of Sertoli cells and Sertoli germ cells, are required for spermatogenesis and sperm release. Here, we show that Wnt5a, a noncanonical Wnt signaling pathway ligand, is predominately expressed in both the BTB and apical ES and has a specific expression pattern during the seminiferous epithelium cycle. We employed siRNA to knockdown Wnt5a expression in testis and Sertoli cells, and then identified elongated spermatids that lost their polarity and were embedded in the seminiferous epithelium. Moreover, phagosomes were found near the tubule lumen. These defects were due to BTB and apical ES disruption. We also verified that the expression level and/or location of BTB-associated proteins, actin binding proteins (ABPs), and F-actin was changed after Wnt5a knockdown in vivo and in vitro. Additionally, we demonstrated that Wnt5a regulated actin dynamics through Ror2-mediated mTORC1 and mTORC2. This study clarified the molecular mechanism of Wnt5a in Sertoli cell junctions through the planar cell polarity (PCP) signaling pathway. Our findings could provide an experimental basis for the clinical diagnosis and treatment of male infertility caused by Sertoli cell junction impairment.
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http://dx.doi.org/10.1210/endocr/bqab149DOI Listing
October 2021

Bi-allelic truncating variants in CFAP206 cause male infertility in human and mouse.

Hum Genet 2021 Sep 13;140(9):1367-1377. Epub 2021 Jul 13.

Université Grenoble Alpes, INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences, Team Genetics Epigenetics and Therapies of Infertility, 38000, Grenoble, France.

Spermatozoa are polarized cells with a head and a flagellum joined together by the connecting piece. Flagellum integrity is critical for normal sperm function, and flagellum defects consistently lead to male infertility. Multiple morphological abnormalities of the flagella (MMAF) is a distinct sperm phenotype consistently leading to male infertility due to a reduced or absent sperm motility associated with severe morphological and ultrastructural flagellum defects. Despite numerous genes recently described to be recurrently associated with MMAF, more than half of the cases analyzed remain unresolved, suggesting that many yet uncharacterized gene defects account for this phenotype. By performing a retrospective exome analysis of the unsolved cases from our initial cohort of 167 infertile men with a MMAF phenotype, we identified one individual carrying a homozygous frameshift variant in CFAP206, a gene encoding a microtubule-docking adapter for radial spoke and inner dynein arm. Immunostaining experiments in the patient's sperm cells demonstrated the absence of WDR66 and RSPH1 proteins suggesting severe radial spokes and calmodulin and spoke-associated complex defects. Using the CRISPR-Cas9 technique, we generated homozygous Cfap206 knockout (KO) mice which presented with male infertility due to functional, structural and ultrastructural sperm flagellum defects associated with a very low rate of embryo development using ICSI. Overall, we showed that CFAP206 is essential for normal sperm flagellum structure and function in human and mouse and that bi-allelic mutations in CFAP206 cause male infertility in man and mouse by inducing morphological and functional defects of the sperm flagellum that may also cause ICSI failures.
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http://dx.doi.org/10.1007/s00439-021-02313-zDOI Listing
September 2021

Liver and urine metabolomics reveal the protective effect of Gandou decoction in copper-laden Hepatolenticular degeneration model rats.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Aug 2;1179:122844. Epub 2021 Jul 2.

The Experimental Research Center, Anhui University of Chinese Medicine, Hefei 230038, China; Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei 230012, China. Electronic address:

Hepatolenticular degeneration (HLD) is an inherited disorder associated with human copper metabolism. Gandou decoction (GDD), a traditional Chinese medicinal formula, has been used as a therapeutic agent for the treatment of HLD in China for decades. Recent pharmacological evaluation in our laboratory has demonstrated that GDD exerts positive and beneficial effects on HLD model rats. However, its underlying therapeutic mechanisms are not yet well understood. To explore the potential therapeutic effects of GDD against HLD, liver and urine metabolomics approach combined with histopathological examination were performed to reveal the underlying mechanisms. Changes in metabolic profiles were estimated by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) coupled with multivariate statistical analyses. The results indicated that GDD could significantly improve liver pathological variations. Moreover, 19 and 11 significantly altered metabolites were found in the liver and urine between the normal and model groups, respectively. After GDD treatment, the levels of all these disordered metabolites showed different degrees of improvement compared with the model group, including lysoPC(18:2), lysoPE(20:2/0:0), PC(18:1/14:1), alpha-linolenic acid, sphinganine, taurochenodesoxycholic acid, tetracosahexaenoic acid, 13-OxoODE, and 13-L-hydroperoxyl inoleic acid. Metabolic pathway enrichment suggested that lipid and oxidative stress metabolism were the two main pathways that participated in copper-laden rat models with GDD administration. This work indicates that GDD could achieve a therapeutic effect on HLD by ameliorating the associated metabolic disturbances.
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http://dx.doi.org/10.1016/j.jchromb.2021.122844DOI Listing
August 2021

Bi-allelic mutations of DNAH10 cause primary male infertility with asthenoteratozoospermia in humans and mice.

Am J Hum Genet 2021 08 7;108(8):1466-1477. Epub 2021 Jul 7.

Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha 410000, China; Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha 410000, China. Electronic address:

Multiple morphological abnormalities of the sperm flagella (MMAF)-induced asthenoteratozoospermia is a common cause of male infertility. Previous studies have identified several MMAF-associated genes, highlighting the condition's genetic heterogeneity. To further define the genetic causes underlying MMAF, we performed whole-exome sequencing in a cohort of 643 Chinese MMAF-affected men. Bi-allelic DNAH10 variants were identified in five individuals with MMAF from four unrelated families. These variants were either rare or absent in public population genome databases and were predicted to be deleterious by multiple bioinformatics tools. Morphological and ultrastructural analyses of the spermatozoa obtained from men harboring bi-allelic DNAH10 variants revealed striking flagellar defects with the absence of inner dynein arms (IDAs). DNAH10 encodes an axonemal IDA heavy chain component that is predominantly expressed in the testes. Immunostaining analysis indicated that DNAH10 localized to the entire sperm flagellum of control spermatozoa. In contrast, spermatozoa from the men harboring bi-allelic DNAH10 variants exhibited an absence or markedly reduced staining intensity of DNAH10 and other IDA components, including DNAH2 and DNAH6. Furthermore, the phenotypes were recapitulated in mouse models lacking Dnah10 or expressing a disease-associated variant, confirming the involvement of DNAH10 in human MMAF. Altogether, our findings in humans and mice demonstrate that DNAH10 is essential for sperm flagellar assembly and that deleterious bi-allelic DNAH10 variants can cause male infertility with MMAF. These findings will provide guidance for genetic counseling and insights into the diagnosis of MMAF-associated asthenoteratozoospermia.
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http://dx.doi.org/10.1016/j.ajhg.2021.06.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387467PMC
August 2021

[Rapid identification of chemical components in Qi-Yu-San-Long decoction by ultra high performance liquid chromatography-quadrupole time-of-flight mass spectrometry].

Se Pu 2021 Jul;39(7):730-743

Scientific Research & Experiment Center, Anhui University of Chinese Medicine, Hefei 230038, Chin.

Qi-Yu-San-Long decoction (QYSLD) is a classic traditional Chinese medicine prescription consisting of ten types of herbal medicines, including Astragali Radix, Polygonati Odorati Rhizoma, Scolopendra, Pheretima, L., Willd., Coicis Semen, L., Curcumae Rhizoma, and Fritillariae Cirrhosae Bulbus, combined in a ratio of 15∶5∶3∶3∶10∶10∶10∶3∶5∶3 by weight. QYSLD has been used to treat non-small cell lung cancer (NSCLC) for over 20 years in clinical practice, and its curative effect is considered credible. However, the chemical constituents of QYSLD have not been revealed because of their complexity, which has significantly hindered the systematic clarification of the efficacy of the materials and quality evaluation. In this study, a reliable strategy based on the data-independent acquisition (DIA) technology of ultra high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) combined with a targeted screening method was established to investigate the chemical components of QYSLD. A 2-μL aliquot from each vial was injected into a Waters ACQUITY UPLC BEH C column (100 mm×2.1 mm, 1.7 μm) to separate complex components. The temperature of the column was 35 ℃, and the flow rate was set at 0.2 mL/min. The mobile phase consisted of 0.1% formic acid aqueous solution and acetonitrile. Detection was conducted using an Xevo G2-XS QTOF-MS with a LockSpray capable-electrospray interface. The data for complex components in QYSLD were collected by full-information tandem mass spectrometry (MS ) in the positive and negative ion modes. In the MS mode, data acquisition was performed using a mass spectrometer by rapidly switching from a low-collision-energy (CE) scan to a high-CE scan during a single LC run. Thus, accurate precursor and fragment ions were collected in a single run, which was helpful for the structural elucidation of multiple components in QYSLD. In addition, systematic information on isolated chemical compounds was collected and distinguished from the ten individual herbs in QYSLD using databases such as China Academic Journals Full-text database (CNKI), PubMed, Web of Science, Medline, and ChemSpider. Accordingly, a self-building library of QYSLD, including the component name, molecular formula, and structure of the components from the herbs, was established. Subsequently, the raw MS data of the collected samples and the self-building chemical composition library were imported into a natural product post-processing screening (UNIFI) platform for targeted screening of the chemical components in QYSLD. The parameters for UNIFI platform were as follows: the retention time deviation was ±0.1 min; an error margin of no more than 5×10 for the identified compounds was allowed; positive adducts, including [M+H]and [M+Na], were selected; and negative adducts, including [M-H] and [M+HCOO], were selected. The results showed that a total of 166 compounds were initially identified, including 22 saponins, 13 alkaloids, 27 flavonoids, 32 terpenes, 20 amino acids, 16 phenylpropanoids, 9 organic acids, 6 sterols, 6 anthraquinones, and 15 other components. Among them, sixteen components were confirmed unambiguously with the reference substances. To better understand the chemical contribution of individual herbs to the entire decoction, the attributes of each component were summarized. This study provides a foundation for exploring the pharmacodynamic substances of QYSLD.
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http://dx.doi.org/10.3724/SP.J.1123.2020.10016DOI Listing
July 2021

Novel Mutations in X-Linked, -Induced Asthenoteratozoospermia and Male Infertility.

Cells 2021 Jun 25;10(7). Epub 2021 Jun 25.

Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.

Male infertility is a multifactorial disease with a strong genetic background. Abnormal sperm morphologies have been found to be closely related to male infertility. Here, we conducted whole-exome sequencing in a cohort of 150 Han Chinese men with asthenoteratozoospermia. Two novel hemizygous mutations were identified in , an X-linked gene preferentially expressed in the testis and encoding a deubiquitinating enzyme. These variants are extremely rare in human population genome databases and have been predicted to be deleterious by multiple bioinformatics tools. Hematoxylin-eosin staining and electron microscopy analyses of the spermatozoa from men harboring hemizygous variants showed a highly aberrant morphology and ultrastructure of the sperm heads and flagella. Real-time quantitative PCR and immunoblotting assays revealed obviously reduced levels of mRNA and protein in the spermatozoa from men harboring hemizygous deleterious variants of . Furthermore, intracytoplasmic sperm injections performed on infertile men harboring hemizygous variants achieved satisfactory outcomes. Overall, our study demonstrates that is essential for normal sperm morphogenesis, and hemizygous mutations can induce X-linked asthenoteratozoospermia. These findings will provide effective guidance for the genetic and reproductive counseling of infertile men with asthenoteratozoospermia.
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http://dx.doi.org/10.3390/cells10071594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307012PMC
June 2021

Identification of Novel Biallelic Variants in Female Infertility With Preimplantation Embryonic Lethality.

Front Genet 2021 11;12:666136. Epub 2021 Jun 11.

Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Preimplantation embryonic lethality is a rare cause of primary female infertility. It has been reported that variants in the transducin-like enhancer of split 6 () gene can lead to preimplantation embryonic lethality. However, the incidence of variants in patients with preimplantation embryonic lethality is not fully understood. In this study, we identified four patients carrying novel biallelic variants in a cohort of 28 patients with preimplantation embryonic lethality by whole-exome sequencing and bioinformatics analysis, accounting for 14.29% (4/28) of the cohort. Immunofluorescence showed that the TLE6 levels in oocytes from patients were much lower than in normal control oocytes, suggesting that the variants result in the lower expression of the TLE6 protein in oocytes. In addition, a retrospective analysis showed that the four patients underwent a total of nine failures of fertilization and intracytoplasmic sperm injection attempts, and one of them became pregnant on the first attempt using donated oocytes. Our study extends the genetic spectrum of female infertility caused by variants in and further confirms previously reported findings that TLE6 plays an essential role in early embryonic development. In such case, oocyte donation may be the preferred treatment.
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http://dx.doi.org/10.3389/fgene.2021.666136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226231PMC
June 2021

Loss of DRC1 function leads to multiple morphological abnormalities of the sperm flagella and male infertility in human and mouse.

Hum Mol Genet 2021 Jun 24. Epub 2021 Jun 24.

State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, China.

Motile cilia and flagellar defects can result in primary ciliary dyskinesia (PCD), which is a multisystemic genetic disorder that affects roughly 1:10000 individuals. The nexin-dynein regulatory complex (N-DRC) links neighboring doublet microtubules within flagella, serving as a central regulatory hub for motility in Chlamydomonas. Herein, we identified two homozygous DRC1 variants in human patients that were associated with multiple morphological abnormalities of the sperm flagella (MMAF) and male infertility. Drc1-/-, Drc1R554X/R554X, and Drc1W244X/W244X mice on the C57BL/6 background suffered from prepubertal mortality. However, when the ICR background was introduced, some of these mice were able to survive and recapitulate the MMAF phenotypes detected in human patients. By analyzing these animals, we determined that DRC1 is an essential regulator of N-DRC assembly in cilia and flagella. When DRC1 is absent, this results in the shortening of cilia and consequent impairment of their motility. Damage associated with DRC1 deficiency in sperm flagella was more pronounced than in cilia, as manifested by complete axoneme structural disorder in addition to the loss of the DRC structure. Together, these findings suggest that DRC1 is required for the structural stability of flagella but not cilia, emphasizing the key role of this protein in mammalian species.
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http://dx.doi.org/10.1093/hmg/ddab171DOI Listing
June 2021

Establishment of an induced pluripotent stem cell line from a patient with primary ciliary dyskinesia carrying biallelic mutations in CCNO.

Stem Cell Res 2021 05 29;53:102372. Epub 2021 Apr 29.

Reproductive Medicine Center, Department of Obstetrics and Gynecology, First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China. Electronic address:

Primary ciliary dyskinesia (PCD) is an autosomal recessive hereditary disorder affecting motile cilia structure and function, which leads to respiratory diseases and infertility. Here, an induced pluripotent stem cell (iPSC) line of PCD was generated from peripheral blood mononuclear cells of a female patient carrying biallelic mutations in Cyclin O (CCNO) gene. Reprogramming was performed with the non-integrated episomal vectors. The obtained transgene-free iPSCs had normal karyotypes, expressed pluripotency genes, and differentiated into three germ layers. This iPSC line could be a useful guide for studying the pathogenic mechanism, establishing a disease model of PCD, and screening potential therapeutic targets.
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http://dx.doi.org/10.1016/j.scr.2021.102372DOI Listing
May 2021

Interference fading suppression in φ-OTDR using space-division multiplexed probes.

Opt Express 2021 May;29(10):15452-15462

We propose and experimentally demonstrate a novel interference fading suppression method for phase-sensitive optical time domain reflectometry (φ-OTDR) using space-division multiplexed (SDM) pulse probes in a few-mode fiber. The SDM probes consist of multiple different modes, and three spatial modes (LP01, LP11a, and LP11b) are used in this work for the proof of concept. Firstly, the Rayleigh backscattering light of different modes is experimentally characterized, and it turns out that the waveforms of the φ-OTDR traces for distinct modes are all different and independent. Thanks to the spatial difference of the fading positions for distinct modes, multiple probes from spatially multiplexed modes can be used to suppress the interference fading in φ-OTDR. Then, the performances of the φ-OTDR systems using a single probe and multiple probes are evaluated and compared. Specifically, the statistical analysis shows that the fading probabilities over both the fiber length and the time scale are reduced significantly by using multiple SDM probes, which verifies the significant performance improvement on fading suppression. By introducing the concept of SDM to φ-OTDR, the proposed novel interference fading suppression method avoids the complicated frequency or phase modulation, which has the advantages of simplicity, good effectiveness and high reliability.
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http://dx.doi.org/10.1364/OE.422608DOI Listing
May 2021

De novo transcriptome assembly of Angelica dahurica and characterization of coumarin biosynthesis pathway genes.

Gene 2021 Jul 9;791:145713. Epub 2021 May 9.

Anhui University of Chinese Medicine and Anhui Academy of Chinese Medicine, Hefei 230038, China; Synergetic Innovation Center of Anhui Authentic Chinese Medicine Quality Improvement, Hefei 230012, China. Electronic address:

Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav (A. dahurica) is a famous Chinese herb known for the production of coumarins, important secondary metabolites with wide-ranging pharmacological activities. In particular, the methoxylated coumarins like those produced by A. dahurica are known for their anti-inflammatory, anti-cancer, and anti-oxidant pharmacological effects. However, the molecular mechanism of coumarin biosynthesis in A. dahurica has not been studied. Such investigation could help scientists harness the biosynthesis potential of methoxylated coumarins. Here we present, three transcriptomes corresponding to leaf, root, and stem tissues of A. dahurica. A total of 114,310 unigenes with an average length of 1118 bp were de novo assembled, and 81,404 (71.21%) of those unigenes were annotated. Then, 181 unigenes encoding the seven key enzymes involved were identified, for which COMT (Caffeic acid 3-O-methyltransferase) was spatially used in a phylogenetic analysis, and some of these key enzyme genes were verified by qRT-PCR. Differentially expressed genes and root-specific-expressed genes were identified, by comparing genes' profile activity between roots and other tissues. Furthermore, multiple genes encoding key enzymes or transcription factors related to coumarin biosynthesis were identified and analyzed. This study is the first to report comprehensive gene information of A. dahurica at the transcriptional level, and to distinguish candidate genes related to its biosynthesis of coumarin, thus laying a foundation for this pathway's further exploration in A. dahurica.
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http://dx.doi.org/10.1016/j.gene.2021.145713DOI Listing
July 2021

Genome-wide identification and expression pattern analysis of lipoxygenase gene family in banana.

Sci Rep 2021 May 11;11(1):9948. Epub 2021 May 11.

College of Horticulture, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.

The LOX genes have been identified and characterized in many plant species, but studies on the banana LOX genes are very limited. In this study, we respectively identified 18 MaLOX, 11 MbLOX, and 12 MiLOX genes from the Musa acuminata, M. balbisiana and M. itinerans genome data, investigated their gene structures and characterized the physicochemical properties of their encoded proteins. Banana LOXs showed a preference for using and ending with G/C and their encoded proteins can be classified into 9-LOX, Type I 13-LOX and Type II 13-LOX subfamilies. The expansion of the MaLOXs might result from the combined actions of genome-wide, tandem, and segmental duplications. However, tandem and segmental duplications contribute to the expansion of MbLOXs. Transcriptome data based gene expression analysis showed that MaLOX1, 4, and 7 were highly expressed in fruit and their expression levels were significantly regulated by ethylene. And 11, 12 and 7 MaLOXs were found to be low temperature-, high temperature-, and Fusarium oxysporum f. sp. Cubense tropical race 4 (FocTR4)-responsive, respectively. MaLOX8, 9 and 13 are responsive to all the three stresses, MaLOX4 and MaLOX12 are high temperature- and FocTR4-responsive; MaLOX6 and MaLOX17 are significantly induced by low temperature and FocTR4; and the expression of MaLOX7 and MaLOX16 are only affected by high temperature. Quantitative real-time PCR (qRT-PCR) analysis revealed that the expression levels of several MaLOXs are regulated by MeJA and FocTR4, indicating that they can increase the resistance of banana by regulating the JA pathway. Additionally, the weighted gene co-expression network analysis (WGCNA) of MaLOXs revealed 3 models respectively for 5 (MaLOX7-11), 3 (MaLOX6, 13, and 17), and 1 (MaLOX12) MaLOX genes. Our findings can provide valuable information for the characterization, evolution, diversity and functionality of MaLOX, MbLOX and MiLOX genes and are helpful for understanding the roles of LOXs in banana growth and development and adaptations to different stresses.
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http://dx.doi.org/10.1038/s41598-021-89211-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113564PMC
May 2021

Comprehensive RNA-Seq Analysis of Potential Therapeutic Targets of Gan-Dou-Fu-Mu Decoction for Treatment of Wilson Disease Using a Toxic Milk Mouse Model.

Front Pharmacol 2021 15;12:622268. Epub 2021 Apr 15.

Department of Pharmacy, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China.

Gan-Dou-Fu-Mu decoction (GDFMD) improves liver fibrosis in experimental and clinical studies including those on toxic mouse model of Wilson disease (Model). However, the mechanisms underlying the effect of GDFMD have not been characterized. Herein, we deciphered the potential therapeutic targets of GDFMD using transcriptome analysis. We constructed a tx-j Wilson disease (WD) mouse model, and assessed the effect of GDFMD on the liver of model mice by hematoxylin and eosin, Masson, and immunohistochemical staining. Subsequently, we identified differentially expressed genes (DEGs) that were upregulated in the Model (Model vs. control) and those that were downregulated upon GDFMD treatment (compared to the Model) using RNA-sequencing (RNA-Seq). Biological functions and signaling pathways in which the DEGs were involved were determined by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses. A protein-protein interaction (PPI) network was constructed using the STRING database, and the modules were identified using MCODE plugin with the Cytoscape software. Several genes identified in the RNA-Seq analysis were validated by real-time quantitative PCR. Total of 2124 DEGs were screened through the Model vs. control and Model vs. GDFMD comparisons, and dozens of GO and KEGG pathway terms modulated by GDFMD were identified. Dozens of pathways involved in metabolism (including metabolic processes for organic acids, carboxylic acids, monocarboxylic acids, lipids, fatty acids, cellular lipids, steroids, alcohols, eicosanoids, long-chain fatty acids), immune and inflammatory response (such as complement and coagulation cascades, cytokine-cytokine receptor interaction, inflammatory mediator regulation of TRP channels, antigen processing and presentation, T-cell receptor signaling pathway), liver fibrosis (such as ECM-receptor interactions), and cell death (PI3K-Akt signaling pathway, apoptosis, TGF-beta signaling pathway, etc.) were identified as potential targets of GDFMD in the Model. Some hub genes and four modules were identified in the PPI network. The results of real-time quantitative PCR analysis were consistent with those of RNA-Seq analysis. We performed gene expression profiling of GDFMD-treated WD model mice using RNA-Seq analysis and found the genes, pathways, and processes effected by the treatment. Our study provides a theoretical basis to prevent liver fibrosis resulting from WD using GDFMD.
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http://dx.doi.org/10.3389/fphar.2021.622268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082393PMC
April 2021

Degradation and Transformation of Lignin by a Fungus Strain F-1.

Iran J Biotechnol 2020 Jul 1;18(3):e2461. Epub 2020 Jul 1.

School of Food and Biological Engineering, Hefei University of Technology, Hefei, China.

Background: Lignin is the largest natural aromatic polymer in nature and is also a unique aromatic-based biopolymer, accounting for nearly 30% of the earth's organic carbon. Generally, lignin is regarded as waste and is mainly used as a low- value fuel that is burned to generate heat and energy to solve the problem of biomass waste; for this obstacle of lignin, highly efficient biodegradation plays a critical role in developing an environmentally friendly technique for lignin biotransformation.

Objectives: This study intends to isolate and purify several microbial strains from nature. It also explores how their lignin degradation is able to enhance the biodegradation and recycling of biomass and the reclamation of lignin in wastewater from pulp and paper mills.

Materials And Methods: Lignin-degrading microbial strains were isolated from soil using medium containing sodium lignosulphonate as the sole carbon source. They were then screened by aniline blue and guaiacol plate, and then the best strain was chosen and identified. The conventional one-factor method was used to optimize various parameters that affect lignin's degradation ability.

Results: The strain possessing the highest lignin biodegradation ability was identified and denominated as F-1. After optimization, the maximum degradation rate of lignin, 44.6% within 3 days, was obtained at pH 7.0, 30 ℃, 2.5 g·L ammonium sulfate, 2 g·L lignin and 0.5 g·L glucose. The results show the LiP and Lac secreted from F-1 played the main role in the degradation of lignin.

Conclusion: One microbial strain, F-1, was successfully isolated with a lignin-degrading ability that can cut the lignin into fragments. This provides a promising candidate for the transformation and utilization of crop waste biomass for various industrial purposes.
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http://dx.doi.org/10.30498/IJB.2020.155690.2461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035421PMC
July 2020

Sperm DNA integrity status is associated with DNA methylation signatures of imprinted genes and non-imprinted genes.

J Assist Reprod Genet 2021 Aug 30;38(8):2041-2048. Epub 2021 Mar 30.

Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China.

Purpose: To evaluate the association between the DNA methylation of specific genes and sperm DNA integrity status in human sperm samples.

Methods: A total of 166 semen samples were evaluated (86 controls and 80 cases with impaired sperm DNA integrity). We detected the methylation status of 257 CpG sites among two imprinted genes (H19 and SNRPN) and four non-imprinted genes related to male infertility (MTHFR, GSTM1, DAZL, and CREM) by using a targeted next-generation sequencing method.

Results: Differential methylation was found in 43 CpG sites of the promoters of the six candidate genes. H19, SNRPN, MTHFR, DAZL, GSTM1, and CREM contained 22, 12, 1, 4, 0, and 4 differentially methylated CpG sites (P<0.05), respectively. The imprinting genes were associated with relatively higher rates of differentially methylated CpG sites (28.21% in H19 and 41.38% in SNRPN) than the non-imprinting genes. One CpG site in H19 remained significant after performing strict Bonferroni correction.

Conclusion: In this study, we found that different site-specific DNA methylation signatures were correlated with sperm DNA integrity status. Further studies are needed to investigate the specific mechanisms leading to the epigenetic modifications.
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http://dx.doi.org/10.1007/s10815-021-02157-6DOI Listing
August 2021

Detection of the chiral drug Ephedrine by resonance Rayleigh scattering based on Ce functionalized gold nanoparticles.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Jul 17;255:119695. Epub 2021 Mar 17.

Chongqing Three Gorges University, Wanzhou, Chongqing 404100, China. Electronic address:

Two chiral drugs, ephedrine (EH) and pseudoephedrine (PEH), were commonly used in clinical treatment. Ephedrine (EH) and pseudoephedrine (PEH) could make different changes in resonance Rayleigh scattering spectrum of the detection system which use Ce functionalized gold nanoparticles as probe. Therefore, a new method of detecting EH and PEH separately was developed. The RRS spectrum and UV-Vis absorption spectrum of AuNPs-Ce detection system was analyzed in order to discuss the mechanism. Under optimal experimental conditions, the linear range of EH and PEH were 20-920 ng/mL and 40-520 ng/mL, respectively. The detection limit were 1.9 ng/mL and 3.8 ng/mL, respectively. Last used for actual testing, this method had obtained good results.
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http://dx.doi.org/10.1016/j.saa.2021.119695DOI Listing
July 2021

Deciphering the metabolic profile and pharmacological mechanisms of Achyranthes bidentata blume saponins using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry coupled with network pharmacology-based investigation.

J Ethnopharmacol 2021 Jun 23;274:114067. Epub 2021 Mar 23.

Anhui University of Chinese Medicine, Hefei, 230012, China; Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui Province Key Laboratory of R&D of Chinese Medicine, Hefei, 230012, China; Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, 230012, China.

Ethnopharmacological Relevance: Achyranthes bidentata Blume (AB) is a traditional Chinese medicine (TCM) widely used as a dietary supplement and anti-arthritis drug. Pharmacological studies have shown that Achyranthes bidentata Blume saponins (ABS) are the main bioactive ingredient. However, the metabolic profile and mechanisms of action of ABS against rheumatic arthritis (RA) remain to be established.

Aim Of The Study: Our main objective was to investigate the metabolic profile and pharmacological activities of ABS against RA.

Materials And Methods: In this study, an analytical method based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) coupled with a metabolism platform was developed for metabolic profiling of ABS in rat liver microsomes and plasma. Then, the in vivo metabolites of ABS and their targets associated with RA were used to construct the network pharmacological analysis. Gene ontology (GO) enrichment, KEGG signaling pathway analyses and pathway network analyses were performed. The therapeutic effect of ABS on RA was further evaluated using an adjuvant arthritis (AA) model and network pharmacology results validated via Western blot.

Results: Overall, 26 and 21 metabolites of ABS were tentatively characterized in rat liver microsomes and plasma, respectively. The metabolic pathways of ABS mainly included M+O, M+O-H, M+O, and M+O-H. Data form network pharmacology analysis suggested that MAPK, apoptosis, PI3K-AKT and p53 signaling pathways contribute significantly to the therapeutic effects of ABS on RA. In pharmacodynamics experiments, ABS ameliorated the symptoms in AA rats in a dose-dependent manner and restored the homeostasis of pro/anti-inflammatory factors. Western blot results further demonstrated a significant ABS-induced decrease in phosphorylation of ERK in the MAPK pathway (P < 0.01).

Conclusion: Application of an analytical method based on UPLC-QTOF/MS, network pharmacology and validation experiments offers novel insights into the components and mechanisms of ABS that contribute to its therapeutic effects against RA, providing useful directions for further research.
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http://dx.doi.org/10.1016/j.jep.2021.114067DOI Listing
June 2021

Novel bi-allelic variants in DNAH2 cause severe asthenoteratozoospermia with multiple morphological abnormalities of the flagella.

Reprod Biomed Online 2021 May 22;42(5):963-972. Epub 2021 Jan 22.

Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei 230032, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, Hefei 230032, China. Electronic address:

Research Question: Multiple morphological abnormalities of the flagella (MMAF) is characterized by excessive immotile spermatozoa with severe flagellar abnormalities in the ejaculate. Previous studies have reported a heterogeneous genetic profile associated with MMAF. What other genetic variants might explain the cause of MMAF?

Design: Whole-exome sequencing was conducted in a cohort of 90 Chinese patients with MMAF. The pathogenicity of identified mutations was assessed through electron microscopy and immunofluorescent examinations.

Results: Three unrelated men with bi-allelic DNAH2 variants were identified. Sanger sequencing verified that the six novel variants originated from every parent. All these variants were located at the conserved domains of DNAH2 and predicted to be deleterious by bioinformatic tools. Haematoxylin and eosin staining and scanning electron microscopy revealed that spermatozoa harbouring DNAH2 variants displayed severely aberrant morphology mainly with absent and short flagella (≥78%). Moreover, transmission electron microscopy revealed the obvious absence of a central pair of microtubules and inner dynein arms in the spermatozoa with mutated DNAH2. Immunofluorescence data further validated these findings, showing reduced DNAH2 protein expression in the spermatozoa with DNAH2 variants, compared with normal spermatozoa. Intracytoplasmic sperm injection using spermatozoa from the three men with mutated DNAH2 resulted in blastocyst formation in all cases. Embryo transfer was carried out in two couples, both resulting in clinical pregnancy.

Conclusions: These experimental and clinical data suggest that bi-allelic DNAH2 variants might induce MMAF-associated asthenoteratozoospermia, which can be overcome through intracytoplasmic sperm injection. These findings contribute to the knowledge of the genetic landscape of asthenoteratozoospermia and clinical counselling of male infertility.
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http://dx.doi.org/10.1016/j.rbmo.2021.01.011DOI Listing
May 2021

Pattern recognition in distributed fiber-optic acoustic sensor using an intensity and phase stacked convolutional neural network with data augmentation.

Opt Express 2021 Feb;29(3):3269-3283

Distributed acoustic sensors (DASs) have the capability of registering faint vibrations with high spatial resolution along the sensing fiber. Advanced algorithms are important for DAS in many applications since they can help extract and classify the unique signatures of different types of vibration events. Deep convolutional neural networks (CNNs), which have powerful spectro-temporal feature learning capability, are well suited for event classification in DAS. Generally, these data-driven methods are highly dependent on the availability of large quantities of training data for learning a mapping from input to output. In this work, to fully utilize the collected information and maximize the power of CNNs, we propose a method to enlarge the useful dataset for CNNs from two aspects. First, we propose an intensity and phase stacked CNN (IP-CNN) to utilize both the intensity and phase information from a DAS with coherent detection. Second, we propose to use data augmentation to further increase the training dataset size. The influence of different data augmentation methods on the performance of the proposed CNN architecture is thoroughly investigated. The experimental results show that the proposed IP-CNN with data augmentation produces a classification accuracy of 88.2% on our DAS dataset with 1km sensing length. This indicates that the usage of both intensity and phase information together with the enlarged training dataset after data augmentation can greatly improve the classification accuracy, which is useful for DAS pattern recognition in real applications.
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http://dx.doi.org/10.1364/OE.416537DOI Listing
February 2021

Gandou Decoction Decreases Copper Levels and Alleviates Hepatic Injury in Copper-Laden Hepatolenticular Degeneration Model Rats.

Front Pharmacol 2020 28;11:582390. Epub 2020 Oct 28.

The Experimental Research Center, Anhui University of Chinese Medicine, Hefei, China.

This study was designed to investigate the therapeutic efficacy and underlying mechanisms of Gandou Decoction (GDD) in copper-laden hepatolenticular degeneration (HLD) model rats. In this study, high-performance liquid chromatography (HPLC) fingerprint analysis and eight representative active components were simultaneously measured for quality control of GDD. The therapeutic effect of GDD in HLD was studied by constructing a rat model of copper-laden HLD. The copper levels in the liver, serum, urine, and feces were quantified by atomic absorption spectrophotometry (AAS). Subsequently, UV-Vis spectrophotometry was used to study the coordination ability of copper ion (Cu) with six representative active components in GDD to explore its potential copper expulsion mechanism. Serological indexes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (AKP) were evaluated. Hepatic indicators including superoxide dismutase (SOD), glutathione (GSH), and the total antioxidant capacity (T-AOC) were determined. Moreover, the liver tissue was stained with hematoxylin-eosin to observe the histological changes. Thirty characteristic fingerprint peaks were used to assess the similarities among 10 samples and showed the similarity was >0.98, indicating a good correlation among the common peaks. Simultaneous quantification of eight markers in GDD was then performed to determine the consistency of quality. GDD could decrease the serum and hepatic copper levels by increasing the urinary and fecal copper content in copper-laden rats. Meanwhile, the results of UV-Vis absorption studies show that six representative active ingredients in GDD can coordinate with Cu, indicating that complexing copper removal may be a potential mechanism for GDD to play a role in copper removal. Serum hepatic enzyme markers AST, ALT, and AKP activities and antioxidant enzyme SOD, T-AOC activities, and GSH level in hepatic tissue showed the protection of GDD against liver injury induced by excessive copper. Additionally, the hepatoprotective effect of GDD was also evidenced by the results of the liver histological evaluation. This study suggested that GDD could reduce the serum and hepatic copper levels through promoting urinary and fecal copper excretion in copper-laden rats. At the same time, GDD could alleviate hepatic injury by inhibition of oxidative stress.
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http://dx.doi.org/10.3389/fphar.2020.582390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970920PMC
October 2020

No significant long-term complications from inadvertent exposure to gonadotropin-releasing hormone agonist during early pregnancy in mothers and offspring: a retrospective analysis.

Reprod Biol Endocrinol 2021 Mar 20;19(1):46. Epub 2021 Mar 20.

Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230022, China.

Background: Administration of gonadotropin-releasing hormone agonist (GnRH-a) in the luteal phase is commonly used for pituitary suppression during in vitro fertilisation (IVF). There is an ineluctable risk of inadvertent exposure of spontaneous pregnancy to GnRH-a. However, little is known about the pregnancy complications and repregnancy outcomes of the affected women and the neurodevelopmental outcomes of the GnRH-a-exposed children.

Methods: Retrospective analysis was used to determine obstetric and repregnancy outcomes after natural conception in 114 women who naturally conceived while receiving GnRH-a during their early pregnancy over the past 17 years. The GnRH-a-exposed children were evaluated to determine their neonatal characteristics and long-term neurodevelopmental outcomes. The outcomes were compared to those of relevant age-matched control groups.

Results: Sixty-five women had 66 live births. The neonatal health outcomes and the incidence of maternal complications were similar in the GnRH-a-exposed and control groups. Thirty-one GnRH-a-exposed children, aged 2-8 years, were available for investigation of neurodevelopment. Except for one case of autism spectrum disorder, the full-scale intelligence quotient score was within the normal range and similar to that of the control group. Most mothers with successful pregnancies and about one-third of the women who had spontaneous abortions were subsequently able to conceive naturally again. IVF is recommended for repregnancy in women who have experienced ectopic pregnancies.

Conclusions: Accidental exposure to GnRH-a in early pregnancy might be safe. Reproductive treatment suggestions for repregnancy should be made with consideration of the outcomes of the previously GnRH-a-exposed spontaneous pregnancy.
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http://dx.doi.org/10.1186/s12958-021-00732-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980339PMC
March 2021

Add-On Chinese Medicine for Coronavirus Disease 2019 (ACCORD): A Retrospective Cohort Study of Hospital Registries.

Am J Chin Med 2021 5;49(3):543-575. Epub 2021 Mar 5.

Hepatic Disease Institute, Hubei Key Laboratory of Theoretical and Applied, Research of Liver and Kidney in Traditional Chinese Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan 430061, P. R. China.

Chinese medicine (CM) was extensively used to treat COVID-19 in China. We aimed to evaluate the real-world effectiveness of add-on semi-individualized CM during the outbreak. A retrospective cohort of 1788 adult confirmed COVID-19 patients were recruited from 2235 consecutive linked records retrieved from five hospitals in Wuhan during 15 January to 13 March 2020. The mortality of add-on semi-individualized CM users and non-users was compared by inverse probability weighted hazard ratio (HR) and by propensity score matching. Change of biomarkers was compared between groups, and the frequency of CMs used was analyzed. Subgroup analysis was performed to stratify disease severity and dose of CM exposure. The crude mortality was 3.8% in the semi-individualized CM user group and 17.0% among the non-users. Add-on CM was associated with a mortality reduction of 58% (HR = 0.42, 95% CI: 0.23 to 0.77, [Formula: see text] = 0.005) among all COVID-19 cases and 66% (HR = 0.34, 95% CI: 0.15 to 0.76, [Formula: see text] = 0.009) among severe/critical COVID-19 cases demonstrating dose-dependent response, after inversely weighted with propensity score. The result was robust in various stratified, weighted, matched, adjusted and sensitivity analyses. Severe/critical patients that received add-on CM had a trend of stabilized D-dimer level after 3-7 days of admission when compared to baseline. Immunomodulating and anti-asthmatic CMs were most used. Add-on semi-individualized CM was associated with significantly reduced mortality, especially among severe/critical cases. Chinese medicine could be considered as an add-on regimen for trial use.
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http://dx.doi.org/10.1142/S0192415X21500257DOI Listing
April 2021

Androgenic and Teratogenic Effects of Iodoacetic Acid Drinking Water Disinfection Byproduct and .

Environ Sci Technol 2021 03 1;55(6):3827-3835. Epub 2021 Mar 1.

Department of Occupational and Environmental Health, School of Public Health, Guangxi Medical University, Shuang Yong Road 22, Nanning, Guangxi 530021, China.

Iodoacetic acid (IAA) is the most genotoxic iodinated disinfection byproduct known in drinking water. Previous studies have shown that IAA may be an endocrine disruptor. However, whether IAA has reproductive and developmental toxicity remains unclear. In this study, the reproductive and developmental toxicity of IAA was evaluated using a battery of and reproductive/developmental toxicity screening tests. The results of E-Screen, uterotrophic, and H295R steroidogenesis assays were negative. The Hershberger bioassay revealed that IAA could induce significant increases in absolute and relative weights of paired Cowper's glands. Moreover, there was an increasing trend in the relative weights of the ventral prostate. The micromass test showed that IAA could inhibit the differentiation of midbrain and limb bud cells. A reproductive/developmental toxicity screening test showed that IAA resulted in significantly increased relative weights of testis and seminal vesicles plus coagulating glands in parental male rats, with a dose-response relationship. IAA could not only induce head congestion in offspring but also decrease litter weight, viability index, and anogenital distance index of male pups on postnatal day 4. All these results indicated that IAA had reproductive and developmental toxicity.
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http://dx.doi.org/10.1021/acs.est.0c06620DOI Listing
March 2021

Inhibitory Effects of Combined Bone Morphogenetic Protein 2, Vascular Endothelial Growth Factor, and Basic Fibroblast Growth Factor on Osteoclast Differentiation and Activity.

Tissue Eng Part A 2021 Apr 13. Epub 2021 Apr 13.

College of Biomedical Engineering, Sichuan University, Chengdu, P.R. China.

Bone morphogenetic protein 2 (BMP-2), vascular endothelial growth factor (VEGF), and basic fibroblast growth factors (bFGF) are important regulators of bone development and bone remodeling involving the coordination of osteoblast-mediated bone formation and osteoclast-mediated bone resorption. The synergistic promotions of these growth factors on osteogenesis in the appropriate combination have been confirmed by a lot of studies, but the effect of this combined application on osteoclastogenesis still remains ambiguous. On the basis of comparing the osteoclastic potentials under stimulation of BMP-2, VEGF, or bFGF alone, this study focused on their combined effects on the differentiation and activity of osteoclasts. Our results showed that osteoclastogenesis was enhanced to some extent under the stimulation of BMP-2, VEGF, or bFGF alone, and the potential of these three growth factors to stimulate osteoclastogenesis was VEGF > BMP-2 > bFGF. However, the treatment with the combination of BMP-2 (50 ng/mL), VEGF (1 ng/mL), and bFGF (10 ng/mL), the most suitable dose combination for osteogenesis optimized in our previous study, weakened osteoclast differentiation confirmed by smaller tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells, lower TRAP activity, and lower expression of dendritic cell-specific transmembrane protein, an important molecule regulating osteoclast fusion. Moreover, BMP-2, VEGF, and bFGF in combination also moderately inhibited the bone-resorbing activity of mature osteoclasts by suppressing the expression of osteoclast-specific genes cathepsin K, and matrix metalloproteinase-9. The underlying molecular mechanisms involved the suppression of the receptor activator of nuclear factor-κB ligand-induced c-Fos levels and the activation of nuclear factor of activated T cells c1, two major transcription factors in osteoclast differentiation. Taken together, our study showed that the combination of BMP-2 (50 ng/mL), VEGF (1 ng/mL), and bFGF (10 ng/mL) promoted osteoblastogenesis but inhibited osteoclastogenesis. Thus, the simultaneous use of BMP-2 (50 ng/mL), VEGF (1 ng/mL), and bFGF (10 ng/mL) in an appropriate combination might improve efficacious bone regeneration in a clinical setting.
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http://dx.doi.org/10.1089/ten.TEA.2020.0325DOI Listing
April 2021

Differences in the Gut Microbiome of Women With and Without Hypoactive Sexual Desire Disorder: Case Control Study.

J Med Internet Res 2021 02 25;23(2):e25342. Epub 2021 Feb 25.

Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Background: The gut microbiome is receiving considerable attention as a potentially modifiable risk factor and therapeutic target for numerous mental and neurological diseases.

Objective: This study aimed to explore and assess the difference in the composition of gut microbes and fecal metabolites between women with hypoactive sexual desire disorder (HSDD) and healthy controls.

Methods: We employed an online recruitment method to enroll "hard-to-reach" HSDD populations. After a stringent diagnostic and exclusion process based on DSM-IV criteria, fecal samples collected from 24 women with HSDD and 22 age-matched, healthy controls underwent microbiome analysis using 16S ribosomal RNA gene sequencing and metabolome analysis using untargeted liquid chromatography-mass spectrometry.

Results: We found a decreased abundance of Ruminococcaceae and increased abundance of Bifidobacterium and Lactobacillus among women with HSDD. Fecal samples from women with HSDD showed significantly altered metabolic signatures compared with healthy controls. The abundance of Bifidobacterium, Lactobacillus, and several fecal metabolites correlated negatively with the sexual desire score, while the number of Ruminococcaceae correlated positively with the sexual desire score in all subjects.

Conclusions: Our analysis of fecal samples from women with HSDD and healthy controls identified significantly different gut microbes and metabolic signatures. These preliminary findings could be useful for developing strategies to adjust the level of human sexual desire by modifying gut microbiota.

Trial Registration: Chinese Clinical Trial Registry ChiCTR1800020321; http://www.chictr.org.cn/showproj.aspx?proj=34267.
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http://dx.doi.org/10.2196/25342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952237PMC
February 2021

Flexible thermal interface based on self-assembled boron arsenide for high-performance thermal management.

Nat Commun 2021 Feb 24;12(1):1284. Epub 2021 Feb 24.

Department of Mechanical and Aerospace Engineering, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA.

Thermal management is the most critical technology challenge for modern electronics. Recent key materials innovation focuses on developing advanced thermal interface of electronic packaging for achieving efficient heat dissipation. Here, for the first time we report a record-high performance thermal interface beyond the current state of the art, based on self-assembled manufacturing of cubic boron arsenide (s-BAs). The s-BAs exhibits highly desirable characteristics of high thermal conductivity up to 21 W/m·K and excellent elastic compliance similar to that of soft biological tissues down to 100 kPa through the rational design of BAs microcrystals in polymer composite. In addition, the s-BAs demonstrates high flexibility and preserves the high conductivity over at least 500 bending cycles, opening up new application opportunities for flexible thermal cooling. Moreover, we demonstrated device integration with power LEDs and measured a superior cooling performance of s-BAs beyond the current state of the art, by up to 45 °C reduction in the hot spot temperature. Together, this study demonstrates scalable manufacturing of a new generation of energy-efficient and flexible thermal interface that holds great promise for advanced thermal management of future integrated circuits and emerging applications such as wearable electronics and soft robotics.
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http://dx.doi.org/10.1038/s41467-021-21531-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904764PMC
February 2021

Clinical characteristics and genotype in Dubin-Johnson syndrome: A case report and review of the literature.

World J Clin Cases 2021 Feb;9(4):878-885

Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang 550001, Guizhou Province, China.

Background: Dubin-Johnson syndrome (DJS) is a benign autosomal recessive liver disease involving mutations of the gene. It is characterized by chronic or intermittent conjugated hyperbilirubinemia, with chronic idiopathic jaundice as the main clinical manifestation. Genetic alterations of the gene are commonly used for diagnosing DJS; however, the causative point mutation in Chinese patients remains unknown. Research on mutations in Chinese DJS patients is extremely rare, and the diagnosis of DJS remains limited. The routine analysis of mutations is helpful for the diagnosis of DJS. Here, we report the clinical characteristics and genotype of an adult female DJS patient. This article is to expound the discovery of more potentially pathogenic variants will that contribute to DJS identification.

Case Summary: This study investigated a woman referred for DJS and involved clinical and genetic analyses. mutations were identified by next-generation sequencing (NGS). The patient showed intermittent jaundice and conjugated hyper-bilirubinemia. Histopathological examinations were consistent with the typical phenotype of DJS. Genetic diagnostic analysis revealed an genotype exhibiting a pathogenic variant, namely c.2443C>T (p.Arg815*), which has not been reported previously in the domestic or foreign literature.

Conclusion: Pathogenic mutations play an important role in the diagnosis of DJS, especially in patients with atypical presentations. Currently, NGS is used in the routine analysis of DJS cases and such tests of further cases will better illuminate the relationship between various genotypes and phenotypes of DJS.
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http://dx.doi.org/10.12998/wjcc.v9.i4.878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852649PMC
February 2021
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