Publications by authors named "Fang Zhou"

807 Publications

Superparamagnetic core-shell electrospun scaffolds with sustained release of IONPs facilitating and bone regeneration.

J Mater Chem B 2021 Sep 8. Epub 2021 Sep 8.

State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210009, China.

Bone tissue engineering (BTE) is a promising approach to recover insufficient bone in dental implantations. However, the clinical application of BTE scaffolds is limited by their low mechanical strength and lack of osteoinduction. In an attempt to circumvent these limitations and improve osteogenesis, we introduced magnetic iron oxide nanoparticles (IONPs) into a core-shell porous electrospun scaffold and evaluated their impact on the physical, mechanical, and biological properties of the scaffold. We used poly(lactic--glycolic acid)/polycaprolactone/beta-tricalcium phosphate (PPT) scaffolds with and without γ-FeO encapsulation, namely PPT-Fe scaffolds and PPT scaffolds, respectively. The γ-FeO used in the PPT-Fe scaffolds was coated with polyglucose sorbitol carboxymethylether and was biocompatible. Structurally, PPT-Fe scaffolds showed uniform iron distribution encapsulated within the resorbable PPT scaffolds, and these scaffolds supported sustainable iron release. Furthermore, compared with PPT scaffolds, PPT-Fe scaffolds showed significantly better physical and mechanical properties, including wettability, superparamagnetism, hardness, tensile strength, and elasticity modulus. tests of rat adipose-derived mesenchymal stem cells (rADSCs) seeded onto the scaffolds showed increased expression of integrin β1, alkaline phosphatase, and osteogenesis-related genes. In addition, enhanced bone regeneration was observed after implanting PPT-Fe scaffolds in rat calvarial bone defects. Thus, we can conclude that the incorporation of IONPs into porous scaffolds for long-term release can provide a new strategy for BTE scaffold optimization and is a promising approach that can offer enhanced osteogenic capacity in clinical applications.
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http://dx.doi.org/10.1039/d1tb01261dDOI Listing
September 2021

Elucidation of Distinct Modular Assemblies of Smoothened Receptor by Bitopic Ligand Measurement.

J Med Chem 2021 Sep 7;64(18):13830-13840. Epub 2021 Sep 7.

iHuman Institute, ShanghaiTech University, Ren Building, 393 Middle Huaxia Road, Shanghai 201210, China.

Class F G protein-coupled receptors are characterized by a large extracellular domain (ECD) in addition to the common transmembrane domain (TMD) with seven α-helixes. For smoothened receptor (SMO), structural studies revealed dissected ECD and TMD, and their integrated assemblies. However, distinct assemblies were reported under different circumstances. Using an unbiased approach based on four series of cross-conjugated bitopic ligands, we explore the relationship between the active status and receptor assembly. Different activity dependency on the linker length for these bitopic ligands corroborates the various occurrences of SMO assembly. These results reveal a rigid "near" assembly for active SMO, which is in contrast to previous results. Conversely, inactive SMO adopts a free ECD, which would be remotely captured at "far" assembly by cholesterol. Altogether, we propose a mechanism of cholesterol flow-caused SMO activation involving an erection of ECD from far to near assembly.
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http://dx.doi.org/10.1021/acs.jmedchem.1c01220DOI Listing
September 2021

Stress Assessment of Vestibular Endurance Training for Civil Aviation Flight Students Based on EEG.

Front Hum Neurosci 2021 19;15:582636. Epub 2021 Aug 19.

Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China.

The main goal of this study is to clarify the electroencephalogram (EEG) characteristics of the stress response caused by vestibular endurance training under real conditions. Ten pilot trainees received a series of acute anti-vertigo training stimulations on the rotary ladder while recording electroencephalographic data (64 electrodes). Afterward, the anti-vertigo ability of the subject was tested for the best performance after 1 month of training and verified whether it is related to the EEG signals we collected before. (1) The absolute power of α waves in the C3 and C4 regions is the same as the difference between 1 min before and 2 min after stimulation, and their activity is enhanced by stimulation. Otherwise, the activation of the C3 region after 5 min of stimulation is still significantly changed. (2) Through Spearman's correlation analysis, we found that the α waves in the C3 and C4 the greater the power change, the better the performance of the subject in the proficient stage. C3 and C4 areas are specific brain regions of the stress response of anti-vertigo endurance training, and the absolute power of the α wave can be used as a parameter for identifying the degree of motion sickness (MS). The absolute power changes of α waves in the C3 and C4 areas are positively correlated with their anti-vertigo potential. Increasing the absolute power of α wave in the C3 and C4 is a manifestation of MS stress adaptability.
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http://dx.doi.org/10.3389/fnhum.2021.582636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417248PMC
August 2021

Rational Remodeling of Atypical Scaffolds for the Design of Photoswitchable Cannabinoid Receptor Tools.

J Med Chem 2021 Sep 3;64(18):13752-13765. Epub 2021 Sep 3.

iHuman Institute, ShanghaiTech University, Pudong, Shanghai 201210, China.

Azobenzene-embedded photoswitchable ligands are the widely used chemical tools in photopharmacological studies. Current approaches to azobenzene introduction rely mainly on the isosteric replacement of typical azologable groups. However, atypical scaffolds may offer more opportunities for photoswitch remodeling, which are chemically in an overwhelming majority. Herein, we investigate the rational remodeling of atypical scaffolds for azobenzene introduction, as exemplified in the development of photoswitchable ligands for the cannabinoid receptor 2 (CB2). Based on the analysis of residue-type clusters surrounding the binding pocket, we conclude that among the three representative atypical arms of the CB2 antagonist, AM10257, the adamantyl arm is the most appropriate for azobenzene remodeling. The optimizing spacer length and attachment position revealed with excellent thermal bistability, decent photopharmacological switchability between its two configurations, and high subtype selectivity. This structure-guided approach gave new impetus in the extension of new chemical spaces for tool customization for increasingly diversified photo-pharmacological studies and beyond.
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http://dx.doi.org/10.1021/acs.jmedchem.1c01088DOI Listing
September 2021

A Novel Fluorescence Probe for the Reversible Detection of Bisulfite and Hydrogen Peroxide Pair in Vitro and in Vivo.

Chem Asian J 2021 Sep 2. Epub 2021 Sep 2.

School of Chemical Engineering, University of Science and Technology Liaoning, Anshan, Liaoning Province, 114051, P. R. China.

The detection of changes in the reactive oxygen species (ROS)/reactive sulfur species (RSS) couple is important for studying the cellular redox state. Herein, we developed a 1,8-naphthalimide-based fluorescence probe (NI) for the reversible detection of bisulfite (HSO ) and hydrogen peroxide (H O ) in vitro and in vivo. NI has been designed with a reactive ethylene unit which specifically reacts with HSO by a Michael addition reaction mechanism, resulting in the quenching of yellow fluorescence at 580 nm and the appearing of green fluorescence at 510 nm upon excitation at 500 nm and 430 nm, respectively. The addition product (NI-HSO ) could be specifically oxidized to form the original C=C bond of NI, recovering the fluorescence emission and color. The detection limits of NI for HSO and NI-HSO for H O were calculated to be 2.05 μM and 4.23 μM, respectively. The reversible fluorescence response of NI towards HSO /H O couple can be repeated for at least five times. NI is reliable at a broad pH range (pH 3.0-11.5) and features outstanding selectivity, which enabled its practical applications in biological and food samples. Monitoring the reversible and dynamic inter-conversion between HSO and H O in vitro and in vivo has been verified by fluorescence imaging in live HeLa cells, adult zebrafish and nude mice. Moreover, NI has been successfully applied to detect of HSO levels in food samples.
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http://dx.doi.org/10.1002/asia.202100926DOI Listing
September 2021

Ginsenoside 20(S)-Rh2 promotes cellular pharmacokinetics and intracellular antibacterial activity of levofloxacin against Staphylococcus aureus through drug efflux inhibition and subcellular stabilization.

Acta Pharmacol Sin 2021 Aug 30. Epub 2021 Aug 30.

Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, 210009, China.

Intracellular Staphylococcus aureus (S. aureus) often causes clinical failure and relapse after antibiotic treatment. We previously found that 20(S)-ginsenoside Rh2 [20(S)-Rh2] enhanced the therapeutic effect of quinolones in a mouse model of peritonitis, which we attributed to the increased concentrations of quinolones within bacteria. In this study, we investigated the enhancing effect of 20(S)-Rh2 on levofloxacin (LVF) from a perspective of intracellular bacteria. In S. aureus 25923-infected mice, coadministration of LVF (1.5 mg/kg, i.v.) and 20(S)-Rh2 (25, 50 mg/kg, i.g.) markedly increased the survival rate, and decreased intracellular bacteria counts accompanied by increased accumulation of LVF in peritoneal macrophages. In addition, 20(S)-Rh2 (1, 5, 10 μM) dose-dependently increased the uptake and accumulation of LVF in peritoneal macrophages from infected mice without drug treatment. In a model of S. aureus 25923-infected THP-1 macrophages, we showed that 20(S)-Rh2 (1, 5, 10 μM) dose-dependently enhanced the intracellular antibacterial activity of LVF. At the cellular level, 20(S)-Rh2 increased the intracellular accumulation of LVF by inhibiting P-gp and BCRP. PK-PD modeling revealed that 20(S)-Rh2 altered the properties of the cell but not LVF. At the subcellular level, 20(S)-Rh2 did not increase the distribution of LVF in lysosomes but exhibited a stronger sensitizing effect in acidic environments. Molecular dynamics (MD) simulations showed that 20(S)-Rh2 improved the stability of the DNA gyrase-LVF complex in lysosome-like acidic conditions. In conclusion, 20(S)-Rh2 promotes the cellular pharmacokinetics and intracellular antibacterial activities of LVF against S. aureus through efflux transporter inhibition and subcellular stabilization, which is beneficial for infection treatment.
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http://dx.doi.org/10.1038/s41401-021-00751-zDOI Listing
August 2021

Effects of multiple modes of UltraPulse fractional CO laser treatment on extensive scarring: a retrospective study.

Lasers Med Sci 2021 Aug 26. Epub 2021 Aug 26.

Department of Plastic and Burn Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Rd, Nanjing, 210029, Jiangsu Province, China.

The main therapeutic options for extensive scarring (e.g., > 20% of the total body surface area, or TBSA) after burns and trauma have focused on conservative treatments, such as compression, moisturization, and topical agent application. However, these treatments may not achieve optimal effects due to the large size and complexity of the scars. UltraPulse fractional CO laser treatment is a novel approach that is currently a subject of intense interest; this treatment is most widely used to improve texture, pliability, and pigmentation in all types of scars. However, no studies on the independent use of UltraPulse fractional CO laser treatment for extensive scars have been reported. This retrospective study evaluated a total of 21 patients, whose scars covered 20 to 65% TBSA. Scar thickness was measured by ultrasonography before treatment. Personalized treatment modalities and parameters were set according to the scar type and thickness. Scar formation and treatment effects were evaluated by photography, the Patient and Observer Scar Assessment Scale (POSAS), and patients' judgment of effectiveness. Where the scars covered joints, joint function was assessed by measuring the maximum range of motion (ROM). With laser therapy, scars became flatter and lighter; furthermore, pruritus, pain, and discomfort decreased significantly. POSAS scores significantly decreased after laser therapy, including the item scores for pain and pruritus. There were no instances of joint contracture, ROM reduction, apparent functional impairment, serious adverse events, or comorbidities. This study demonstrates the safety and efficiency of UltraPulse fractional CO laser treatment for extensive scarring.
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http://dx.doi.org/10.1007/s10103-021-03406-xDOI Listing
August 2021

Catalytically Cleavable Detergent for Membrane Protein Studies.

ACS Omega 2021 Aug 4;6(32):21087-21093. Epub 2021 Aug 4.

iHuman Institute, ShanghaiTech University, Y Building, 393 Middle Huaxia Road, Shanghai 201210, China.

Throughout the studies of membrane proteins (MPs), proper detergents are essential for the preparation of stable aqueous samples. To date, universally applicable detergents have not yet been reported to accommodate the distinct requirements for the highly diversified MPs and at the different stages of MP manipulation. Detergent exchange often has to be performed. We report herein the catalytically cleavable detergents (CatCDs) that can be efficiently removed to facilitate a complete exchange. To this end, functional groups, like propargyl and allyl, are introduced as branched chains or built in the hydrophobic chain close to the hydrophilic head. The representative CatCDs can be used as usual detergents in the extraction and purification of MPs and later be removed upon the addition of catalytic palladium. Mediated by , reconstitution of a transporter protein MsbA into a series of detergents was achieved. The extension of these designs could facilitate the future optimization of other biophysics studies.
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http://dx.doi.org/10.1021/acsomega.1c02894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375090PMC
August 2021

Metformin Attenuates Bone Cancer Pain by Reducing TRPV1 and ASIC3 Expression.

Front Pharmacol 2021 4;12:713944. Epub 2021 Aug 4.

Center for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, China.

Bone cancer pain (BCP) is a common pathologic pain associated with destruction of bone and pathological reconstruction of nervous system. Current treatment strategies in clinical is inadequate and have unacceptable side effects due to the unclear pathology mechanism. In the present study, we showed that transplantation of Walker 256 cells aggravated mechanical allodynia of BCP rats (** < 0.01 vs. Sham), and the expression of ASIC3 (Acid-sensitive ion channel 3) and TRPV1 was obviously enhanced in L4-6 dorsal root ganglions (DRGs) of BCP rats (** < 0.01 vs. Sham). ASIC3 and TRPV1 was mainly expressed in CGRP and IB4 positive neurons of L4-6 DRGs. While, TRPV1 but not ASIC3 was markedly upregulated in L4-6 spinal dorsal horn (SDH) of BCP rats (** < 0.01 vs. Sham). Importantly, intrathecal injection of CPZ (a TRPV1 inhibitor) or Amiloride (an ASICs antagonist) markedly increased the paw withdraw threshold (PWT) of BCP rats response to Von Frey filaments (** < 0.01 vs. BCP + NS). What's more, intraperitoneally injection of Metformin or Vinorelbine markedly elevated the PWT of BCP rats, but reduced the expression of TRPV1 and ASIC3 in L4-6 DRGs and decreased the TRPV1 expression in SDH (* < 0.05, ** < 0.01 vs. BCP + NS). Collectively, these results suggest an effective analgesic effect of Metformin on mechanical allodynia of BCP rats, which may be mediated by the downregulation of ASIC3 and TRPV1.
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http://dx.doi.org/10.3389/fphar.2021.713944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371459PMC
August 2021

Overexpression of miR-378 Alleviates Chronic Sciatic Nerve Injury by Targeting EZH2.

Neurochem Res 2021 Aug 18. Epub 2021 Aug 18.

Department of Anesthesiology, The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, China.

In numerous studies, microRNAs (miRNAs) have been authenticated to play vital roles in the pathophysiology of neuropathic pain and other neurological diseases. In our study, we focused on evaluating miR-378 and its potential effects in neuropathic pain development, as well as the underlying molecular mechanisms. Primarily, a chronic sciatic nerve injury (CCI) rat model was established. Next, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to measure the expression levels of miR-378 and EZH2 mRNA; the EZH2 protein expression levels were detected by western blot. A luciferase activity assay monitored the interaction of miR-378 and EZH2. Mechanical and thermal hyperalgesia was also performed to quantitate the effects of overexpression of miR-378 or EZH2 on the CCI rats. We found that miR-378 was down-regulated in the CCI rats, and the overexpression of miR-378 produced significant relief in their pain management. EZH2 was the downstream gene of miR-378 and was negatively regulated by miR-378. The up-regulation of EZH2 reduced the inhibitory effects of miR-378 on the development of neuropathic pain in the CCI rats. miR-378 acts as an inhibitor in the progression of neuropathic pain via targeting EZH2; the miR-378/EZH2 axis may be a novel target for the diagnosis and therapy of neuropathic pain in clinical treatment.
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http://dx.doi.org/10.1007/s11064-021-03424-9DOI Listing
August 2021

Comparison of solid tissue sequencing and liquid biopsy accuracy in identification of clinically relevant gene mutations and rearrangements in lung adenocarcinomas.

Mod Pathol 2021 Aug 6. Epub 2021 Aug 6.

Departments of Pathology, New York University School of Medicine, New York, NY, USA.

Screening for therapeutic targets is standard of care in the management of advanced non-small cell lung cancer. However, most molecular assays utilize tumor tissue, which may not always be available. "Liquid biopsies" are plasma-based next generation sequencing (NGS) assays that use circulating tumor DNA to identify relevant targets. To compare the sensitivity, specificity, and accuracy of a plasma-based NGS assay to solid-tumor-based NGS we retrospectively analyzed sequencing results of 100 sequential patients with lung adenocarcinoma at our institution who had received concurrent testing with both a solid-tissue-based NGS assay and a commercially available plasma-based NGS assay. Patients represented both new diagnoses (79%) and disease progression on treatment (21%); the majority (83%) had stage IV disease. Tissue-NGS identified 74 clinically relevant mutations, including 52 therapeutic targets, a sensitivity of 94.8%, while plasma-NGS identified 41 clinically relevant mutations, a sensitivity of 52.6% (p < 0.001). Tissue-NGS showed significantly higher sensitivity and accuracy across multiple patient subgroups, both in newly diagnosed and treated patients, as well as in metastatic and nonmetastatic disease. Discrepant cases involved hotspot mutations and actionable fusions including those in EGFR, ALK, and NTRK1. In summary, tissue-NGS detects significantly more clinically relevant alterations and therapeutic targets compared to plasma-NGS, suggesting that tissue-NGS should be the preferred method for molecular testing of lung adenocarcinoma when tissue is available. Plasma-NGS can still play an important role when tissue testing is not possible. However, given its low sensitivity, a negative result should be confirmed with a tissue-based assay.
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http://dx.doi.org/10.1038/s41379-021-00880-0DOI Listing
August 2021

Molecular cytology of the respiratory tract and pleura.

Cytopathology 2021 Aug 1. Epub 2021 Aug 1.

Department of Pathology, New York University Langone Health, New York, NY, USA.

There is growing evidence that molecular testing is feasible on all types of cytological preparation, which is fortunate as more diagnostic markers and biomarkers for targeted therapies are discovered for use in pulmonary and pleural malignancies. In this article we will discuss the pre-analytic, analytic, and post-analytic (interpretive) considerations for successful implementation of molecular tests for diagnostic and predictive markers in respiratory and pleural cytology. The vast majority of laboratories are familiar with, and have validated their molecular protocols for, formalin-fixed paraffin-embedded surgical specimens, which are not directly applicable to cytology specimens. Thus, rigorous validation must be performed for each type of fixative and cytology preparation before it is implemented in the clinical setting.
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http://dx.doi.org/10.1111/cyt.13045DOI Listing
August 2021

Assessment of the feasibility of frozen sections for the detection of spread through air spaces (STAS) in pulmonary adenocarcinoma.

Mod Pathol 2021 Jul 29. Epub 2021 Jul 29.

Department of Pathology, New York University Langone Health, New York, NY, USA.

Spread through air spaces (STAS) is reportedly associated with worse prognosis in sublobar resections of lung adenocarcinoma. Recently, it was proposed that STAS detected on frozen sections can be an indication for lobectomy instead of sublobar resection. We undertook this study to evaluate the reliability of STAS assessment on frozen sections compared to permanent sections, as well as the associations among STAS, tumor grade, and recurrence-free survival (RFS) after sublobar resection. A total of 163 stage I lung adenocarcinoma resections with frozen sections were identified retrospectively. For each case, and for frozen and permanent sections separately, the presence or absence of STAS, as well as the tumor grade, were recorded. Compared to permanent sections, STAS detection on frozen sections had low sensitivity (55%), low positive predictive value (48%), and fair agreement (K = 0.34), whereas there was higher specificity (80%) and negative predictive value (85%). Accuracy was 74%. Tumor grade assessment on frozen sections showed higher sensitivity (77%), positive predictive value (90%), agreement (K = 0.72), specificity (94%), and accuracy (87%), and the same negative predictive value (85%). High-grade histology on frozen sections was associated with shorter RFS (p = 0.02), whereas STAS on frozen sections was not (p = 0.47). Our results suggest that the intraoperative detection of STAS has low sensitivity and positive predictive value. False-positive results may lead to overtreatment of patients with lung cancer. The determination of tumor grade on frozen sections offers better sensitivity and specificity, plus it is associated with RFS, whereas STAS on frozen sections is not. Further study is needed to explore the utility of assessing tumor grade on frozen sections.
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http://dx.doi.org/10.1038/s41379-021-00875-xDOI Listing
July 2021

p16 immunostaining in fine-needle aspirations of the head and neck: determining the optimal positivity threshold in HPV-related squamous cell cancer.

J Am Soc Cytopathol 2021 Jul 7. Epub 2021 Jul 7.

Department of Pathology and New York University Langone Health, New York, New York. Electronic address:

Introduction: There is no consensus for interpretation of p16 immunohistochemistry (IHC) in cytology preparations. Our study aims to assess p16 IHC staining in formalin-fixed cytology cell blocks (CBs) from head and neck squamous cell carcinoma (HNSCC) fine-needle aspiration (FNA) specimens in comparison with surgical pathology p16 staining and to determine the reproducibility of p16 IHC scoring in CBs.

Methods: A total of 40 FNAs from 2014 to 2019 of HNSCC with p16 IHC were obtained. CB p16 staining was scored independently by 5 cytopathologists as interval percentages of tumor cell positivity. Receiver operating characteristic (ROC) curves were examined to determine optimal cutoffs for each pathologist based on sensitivity and specificity values. Gwet's coefficient (AC) was calculated to assess inter-rater reliability.

Results: Greater than 10% was the lowest threshold to reach 100% specificity with high sensitivity (55%-84%) in all 5 raters. Rater performances were similar, with areas under the curve (AUCs) ranging from 0.89 to 0.95. Using the >10% threshold, Gwet's AC = 0.72 (95% CI: 0.56-0.89). Diagnostic performance improved further when low-cellularity cases were excluded, with AUC ranging from 0.94 to 0.99 and Gwet's AC = 0.79 (95% CI: 0.61-0.98).

Conclusion: p16 IHC performed on cytology CBs can serve as a surrogate marker for the detection of HPV with high sensitivity and specificity levels. Using a threshold lower than that recommended for surgical pathology for the interpretation of p16 positivity may be appropriate for FNA cytology CB preparations. All cytopathologists in our study displayed reproducible high sensitivity and specificity values at the >10% threshold.
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http://dx.doi.org/10.1016/j.jasc.2021.06.008DOI Listing
July 2021

Risk factors for implant failure of intertrochanteric fractures with lateral femoral wall fracture after intramedullary nail fixation.

Injury 2021 Jul 18. Epub 2021 Jul 18.

Department of Orthopedics, Peking University Third Hospital, Beijing 100191, China; Engineering Research Center of Bone and Joint Precision Medicine, Ministry of Education, Beijing 100191, China.

Introduction: Few studies have specifically evaluated the comminution extent of lateral femoral wall (LFW) fracture and risk factors of implant failure in intertrochanteric fractures with LFW fracture. The aim of present study was to evaluate the influence of comminution extent of LFW fracture on implant failure and identify risk factors of implant failure in cases with LFW fracture after intramedullary fixation.

Methods: This retrospective study included 130 intertrochanteric fracture with LFW fracture treated with intramedullary fixation at a teaching hospital over a 13-year period from January 2006 to December 2018. Demographic information, cortical thickness index, the reduction quality, status of medial support, position of the screw/blade and status of lateral femoral wall were collected and compared. The logistic regression analyzes was performed to evaluate risk factors of implant failure in intertrochanteric fractures with LFW fracture after intramedullary nail fixation.

Results: 10 patients (7.69%) suffered from mechanical failure after intramedullary fixation. Univariate analyzes showed that comminuted LFW fracture (OR, 7.625; 95%CI, 1.437~40.446; p = 0.017), poor reduction quality (OR, 49.375; 95%CI, 7.217~337.804; p < 0.001) and loss of medial support (OR, 17.818; 95%CI, 3.537~89.768; p < 0.001) were associated with implant failure. After adjustment for confounding variables, the multivariable logistic regression analyzes showed that poor reduction quality (OR, 11.318; 95%CI, 1.126~113.755; p = 0.039) and loss of medial support (OR, 7.734; 95%CI, 1.062~56.327; p = 0.043) were independent risk factors for implant failure. Whereas, comminuted LFW fracture was not associated with implant failure (p = 0.429).

Conclusions: The comminution extent of the LFW fracture might influence the stability of intertrochanteric fractures; and intramedullary fixation might be an effective treatment method. Furthermore, poor reduction quality and loss of medial support could increaze the risk of implant failure in intertrochanteric fractures with LFW fractures after intramedullary fixation. Therefore, we should pay great emphasis on fracture reduction quality in future.
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http://dx.doi.org/10.1016/j.injury.2021.07.025DOI Listing
July 2021

Prevalence and correlates of lifestyle behavior, anxiety and depression in Chinese college freshman: A cross-sectional survey.

Int J Nurs Sci 2021 Jul 5;8(3):347-353. Epub 2021 Jun 5.

Division of Humanity & Social Sciences, School of Nursing, Peking University, Beijing, China.

Objectives: First-year college students had exposure to unhealthy lifestyle behaviors that correlate with a high prevalence of anxiety and depression. Regarding to the modifiable lifestyle behaviors factors, this study investigated the prevalence and correlation of multiple lifestyle behaviors, anxiety and depression in a sample of Chinese first-year college students.

Methods: Cross-sectional data were extracted from app of health lifestyle behaviors survey from September to October 2019. Anxiety, depression, eating regular meals, consumption of snacks in-between meals, consumption of fruit, dessert and sugar-sweetened beverages, smoking and secondhand smoke exposure, consuming alcohol, physical activity, sedentary time were assessed by self-report. Socio-demographic including age, gender, education, family income, religion, and health condition were captured. Logistic regression was used to explore the association of multiple lifestyle behaviors, anxiety and depression.

Results: Totally 1,017 participants were included in the study. The prevalence of anxiety and depression (from mild to severe) were 40.3% and 45.3%, respectively. In multivariable analyses, religion (believe in Buddhism,  = 2.438, 95%CI: 1.097-5.421; believe in Christian,  = 5.886, 95%CI: 1.604-21.597), gender (Female,  = 1.405, 95%CI: 1.001-1.971), secondhand smoke exposure ( = 1.089, 95%CI: 1.001-1.184), and eating regular meals ( = 0.513, 95%CI: 0.346-0.759) were associated with anxiety. Family income ( = 0.732, 95%CI: 0.596-0.898), eating regular meals ( = 0.641, 95%CI: 0.415-0.990), frequency of breakfast ( = 0.813, 95%CI: 0.690-0.959), with a chronic disease ( = 1.902, 95%CI: 1.335-2.712), and consumption of nocturnal snack ( = 1.337, 95%CI: 1.108-1.612) were associated with depression.

Conclusions: These results highlighted the need for early lifestyle behavior intervention, especially modifying diet patterns considering the background of religion, health condition, and social-economic status in first-year college students to improve their mental health.
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http://dx.doi.org/10.1016/j.ijnss.2021.05.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283720PMC
July 2021

The differentiation of new human CD303 Plasmacytoid dendritic cell subpopulations expressing CD205 and/or CD103 regulated by Non-Small-Cell lung cancer cells.

Int Immunopharmacol 2021 Oct 20;99:107983. Epub 2021 Jul 20.

Department of Experimental and Clinical Immunology, CAS Lamvac Biotech Co., Ltd. Huangpu, Guangzhou, Guangdong, PR China. Electronic address:

CD303 plasmacytoid dendritic cells (pDCs) play an important role in the induction of immune tolerance and antitumor immunity. Here, we focused on the effect of NSCLC cells on the development of CD303 pDC subsets expressing CD205 and/or CD103. The NSCLC cell line H1299 and primary NSCLC cells were incubated with DCs. The protein expression of costimulatory molecules on CD303 pDCs, the production of pro-inflammatory and anti-inflammatory cytokines by CD303 pDCs and the development of CD303 pDC subsets were detected by using flow cytometry. Coculture with NSCLC cells modulates the protein expression of CD86 and HLA-DR on CD303 pDCs. Moreover, NSCLC cells suppressed the production of IL-12 and IL-23 but facilitated the secretion of IL-27 and TGF-β by CD303 pDCs. There were new CD303 pDC subsets expressing CD205 and/or CD103 in healthy donors and NSCLC patients: CD303CD205CD103, CD303CD205CD103, CD303CD205CD103 and CD303CD205CD103 pDCs. NSCLC cells modulated the differentiation of CD303 pDC subpopulations by regulating the protein expression of CD205 and/or CD103 on CD303 pDCs. NSCLC cells may regulate the immune functions of CD303 pDCs by modulating the expression of costimulatory molecules on DCs and the production of pro-inflammatory/anti-inflammatory cytokines by DCs. NSCLC cells also regulate the development of CD303 pDC subsets expressing CD205 and/or CD103. These outcomes may reveal a new cellular mechanism leading to the NSCLC-induced immune-suppressive microenvironment.
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http://dx.doi.org/10.1016/j.intimp.2021.107983DOI Listing
October 2021

Recent advance of ACE2 and microbiota dysfunction in COVID-19 pathogenesis.

Heliyon 2021 Jul 10;7(7):e07548. Epub 2021 Jul 10.

Department of Gastroenterology, Henan Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) and has become the world's most pressing public health threat. Although not as common as respiratory symptoms, a substantial proportion of patients with COVID-19 presented the gastrointestinal symptoms. ACE2, as the receptor of SARS-CoV and SARS-CoV-2, is highly expressed in the epithelia of the epithelium cells in lung and intestine. In addition, ACE2 is essential for the innate immunity, amino acid transportation and the homeostasis of intestinal microecology. The composition of gut microbiota in COVID-19 patients was altered and concordant with inflammatory, which may explain the gastrointestinal symptoms in patients. Here we reviewed and discussed the evolving role for ACE2 and gut microbiota in SARS-CoV-2 infection which might provide innovative approaches to targeting ACE2 and gut microbiota for the COVID-19 therapy.
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http://dx.doi.org/10.1016/j.heliyon.2021.e07548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270732PMC
July 2021

A comprehensive synthesis unveils the mysteries of phosphate-solubilizing microbes.

Biol Rev Camb Philos Soc 2021 Jul 21. Epub 2021 Jul 21.

Institute of Ecological Science, Guangzhou Key Laboratory of Subtropical Biodiversity and Biomonitoring, Guangdong Provincial Key Laboratory of Biotechnology for Plant Development, School of Life Sciences, South China Normal University, Guangzhou, 510631, PR China.

Phosphate-solubilizing microbes (PSMs) drive the biogeochemical cycling of phosphorus (P) and hold promise for sustainable agriculture. However, their global distribution, overall diversity and application potential remain unknown. Here, we present the first synthesis of their biogeography, diversity and utility, employing data from 399 papers published between 1981 and 2017, the results of a nationwide field survey in China consisting of 367 soil samples, and a genetic analysis of 12986 genome-sequenced prokaryotic strains. We show that at continental to global scales, the population density of PSMs in environmental samples is correlated with total P rather than pH. Remarkably, positive relationships exist between the population density of soil PSMs and available P, nitrate-nitrogen and dissolved organic carbon in soil, reflecting functional couplings between PSMs and microbes driving biogeochemical cycles of nitrogen and carbon. More than 2704 strains affiliated with at least nine archaeal, 88 fungal and 336 bacterial species were reported as PSMs. Only 2.59% of these strains have been tested for their efficiencies in improving crop growth or yield under field conditions, providing evidence that PSMs are more likely to exert positive effects on wheat growing in alkaline P-deficient soils. Our systematic genetic analysis reveals five promising PSM genera deserving much more attention.
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http://dx.doi.org/10.1111/brv.12779DOI Listing
July 2021

The role mA RNA methylation is CNS development and glioma pathogenesis.

Mol Brain 2021 07 19;14(1):119. Epub 2021 Jul 19.

Department of Neurosurgery, Cancer Hospital of University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, 310022, People's Republic of China.

Epigenetic abnormalities play a crucial role in many tumors, including glioma. RNA methylation occurs as an epigenetic modification similar to DNA methylation and histone modification. mA methylation is the most common and most intensively studied RNA methylation, which can be found throughout the RNA life cycle and exert biological functions by affecting RNA metabolism. The mA modification is primarily associated with three types of protease, which are encoded by the writer, eraser and reader genes, respectively. It has been shown that the mA methylation has close connections with the occurrence and development of many tumors, including glioma. In this study, the concept and the research progress of mA methylation are reviewed, especially the role of mA methylation in glioma. Moreover, we will discuss how glioma is paving the way to the development of new therapeutic options based on the inhibition of mA deposition.
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http://dx.doi.org/10.1186/s13041-021-00831-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290532PMC
July 2021

Sesame β-ketoacyl-acyl carrier protein synthase I regulates pollen development by interacting with an adenosine triphosphate-binding cassette transporter in transgenic Arabidopsis.

Physiol Plant 2021 Jul 16. Epub 2021 Jul 16.

Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture of the People's Republic of China, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, Wuhan, China.

Male gametogenesis is an important biological process critical for seed formation and successful breeding. Understanding the molecular mechanisms of male fertility might facilitate hybrid breeding and increase crop yields. Sesame anther development is largely unknown. Here, a sesame β-ketoacyl-[acyl carrier protein] synthase I (SiKASI) was cloned and characterized as being involved in pollen and pollen wall development. Immunohistochemical analysis showed that the spatiotemporal expression of SiKASI protein was altered in sterile sesame anthers compared with fertile anthers. In addition, SiKASI overexpression in Arabidopsis caused male sterility. Cytological observations revealed defective microspore and pollen wall development in SiKASI-overexpressing plants. Aberrant lipid droplets were detected in the tapetal cells of SiKASI-overexpressing plants, and most of the microspores of transgenic plants contained few cytoplasmic inclusions, with irregular pollen wall components embedded on their surfaces. Moreover, the fatty acid metabolism and the expression of a sporopollenin biosynthesis-related gene set were altered in the anthers of SiKASI-overexpressing plants. Additionally, SiKASI interacted with an adenosine triphosphate (ATP)-binding cassette (ABC) transporter. Taken together, our findings suggested that SiKASI was crucial for fatty acid metabolism and might interact with ABCG18 for normal pollen fertility in Arabidopsis.
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http://dx.doi.org/10.1111/ppl.13501DOI Listing
July 2021

The Common Thread: A Case of Synchronous Lung Cancers and a Germline CHEK2 Mutation.

Clin Lung Cancer 2021 Jun 12. Epub 2021 Jun 12.

NYU Langone Health, Perlmutter Cancer Center, department of Pathology, New York, NY.

Patients with one form of cancer are at increased risk for another, and this is true for lung cancer, where synchronous primary lung cancers are an increasing multifaceted challenge. Here, we present the case of a middle age woman who was found to have bilateral lung masses. Biopsy and subsequent testing revealed unique synchronous lung adenocarcinomas, each with unique genetic signatures. Despite having two unique tumors, she was found to have CHEK2 mutations in both tumors and in germline testing. Because of this extensive testing that showed unique tumors, she was ultimately diagnosed with stage IIIb and IA2 lung cancers, and this changed her treatment options. Consideration of unique primary tumors leads to thorough diagnostics, which changed this patient's diagnosis, prognosis, and treatment. We hope this case raises awareness for multiple primary tumors, as well as CHEK2 as an important oncogene.
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http://dx.doi.org/10.1016/j.cllc.2021.05.011DOI Listing
June 2021

Intravitreal Conbercept for Idiopathic Choroidal Neovascularization in Nursing Women.

Breastfeed Med 2021 Jul 1. Epub 2021 Jul 1.

Department of Ophthalmology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

To report the clinical course and vascular endothelial growth factor (VEGF) levels in breast milk among three nursing women diagnosed with idiopathic choroidal neovascularization (CNV) before and after intravitreal injection of conbercept. This was an observational case series. The main outcomes and measures included best-corrected visual acuity (BCVA), anatomical features using optical coherence tomography, and breast milk concentrations of VEGF before and after the intravitreal injection of conbercept. BCVA was increased, and no ocular or systemic safety problems were observed in any of the three patients during the follow-up period. An enzyme-linked immunosorbent assay was used to measure VEGF concentrations in the breast milk samples. Samples were collected 1 day before and 1, 7, and 30 days after the first intravitreal injection of conbercept. After conbercept injection, VEGF levels in breast milk were slightly decreased and did not change significantly in the following week; levels recovered fully by 30 days post-treatment. Intravitreal injection of conbercept shows favorable effectiveness and safety in the treatment of idiopathic CNV in nursing women and does not result in a significant reduction in VEGF in human breast milk.
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http://dx.doi.org/10.1089/bfm.2021.0097DOI Listing
July 2021

Imaging Course of Lung Transplantation: From Patient Selection to Postoperative Complications.

Radiographics 2021 Jul-Aug;41(4):1043-1063

From the Department of Radiology (S.J.K., L.A., J.P.K., W.H.M.), Department of Pathology (F.Z., N.N., A.L.M.), Department of Pulmonology, Critical Care, and Sleep Medicine (L.A.), and Transplant Institute (L.A.), New York University, New York, NY; Department of Radiology, Mater Misericordiae University Hospital, Dublin, Ireland (B.D.H.); and Department of Pathology, Vancouver Island Health Authority and University of British Columbia, Victoria, British Columbia, Canada (H.S.).

Lung transplant is increasingly performed for the treatment of end-stage lung disease. As the number of lung transplants and transplant centers continues to rise, radiologists will more frequently participate in the care of patients undergoing lung transplant, both before and after transplant. Potential donors and recipients undergo chest radiography and CT as part of their pretransplant assessment to evaluate for contraindications to transplant and to aid in surgical planning. After transplant, recipients undergo imaging during the postoperative hospitalization and also in the long-term outpatient setting. Radiologists encounter a wide variety of conditions leading to end-stage lung disease and a myriad of posttransplant complications, some of which are unique to lung transplantation. Familiarity with these pathologic conditions, including their imaging findings and their temporal relationship to the transplant, is crucial to accurate radiologic interpretation. Knowledge of the surgical techniques and expected postoperative appearance prevents confusing normal posttransplant imaging findings with complications. A basic understanding of the indications, contraindications, and surgical considerations of lung transplant aids in imaging interpretation and protocoling and also facilitates communication between radiologists and transplant physicians. Despite medical and surgical advances over the past several decades, lung transplant recipients currently have an average posttransplant life expectancy of only 6.7 years. As members of the transplant team, radiologists can help maximize patient survival and hopefully increase posttransplant life expectancy and quality of life in the coming decades. RSNA, 2021 .
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http://dx.doi.org/10.1148/rg.2021200173DOI Listing
July 2021

High-throughput screening and rational design of biofunctionalized surfaces with optimized biocompatibility and antimicrobial activity.

Nat Commun 2021 06 18;12(1):3757. Epub 2021 Jun 18.

Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, University of Oklahoma, Norman, OK, USA.

Peptides are widely used for surface modification to develop improved implants, such as cell adhesion RGD peptide and antimicrobial peptide (AMP). However, it is a daunting challenge to identify an optimized condition with the two peptides showing their intended activities and the parameters for reaching such a condition. Herein, we develop a high-throughput strategy, preparing titanium (Ti) surfaces with a gradient in peptide density by click reaction as a platform, to screen the positions with desired functions. Such positions are corresponding to optimized molecular parameters (peptide densities/ratios) and associated preparation parameters (reaction times/reactant concentrations). These parameters are then extracted to prepare nongradient mono- and dual-peptide functionalized Ti surfaces with desired biocompatibility or/and antimicrobial activity in vitro and in vivo. We also demonstrate this strategy could be extended to other materials. Here, we show that the high-throughput versatile strategy holds great promise for rational design and preparation of functional biomaterial surfaces.
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http://dx.doi.org/10.1038/s41467-021-23954-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213795PMC
June 2021

[Comparison of the effectiveness of the posterior malleolus fixed or not on treatment of different Haraguchi's classification of posterior malleolus fractures].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Jun;35(6):722-728

Department of Spinal Surgery, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou Zhejiang, 310000, P.R.China.

Objective: To investigate the effectiveness of fixation the posterior malleolus or not to treat different Haraguchi's classification of posterior malleolus fractures.

Methods: The clinical data of 86 trimalleolar fracture patients who were admitted between January 2015 and September 2019 and met the selection criteria were retrospectively reviewed. There were 29 males and 57 females; the age ranged from 26 to 82 years with a mean age of 55.2 years. According to Haraguchi's classification, 38 patients were in type Ⅰ group, 30 patients in type Ⅱ group, and 18 patients in type Ⅲ group. There was no significant difference in the general data such as gender, age, and fracture location among the 3 groups ( >0.05). The fixation of the posterior malleolus was performed in 23, 21, and 5 patients in type Ⅰ, Ⅱ, and Ⅲ groups, respectively. The operation time, fracture healing time, full weight-bearing time, postoperative joint flatness, and joint degeneration degree of the patients in each group were recorded and compared. The American Orthopedic Foot and Ankle Society (AOFAS) ankle and hindfoot score was used to evaluate ankle function, including pain, quality of daily life, joint range of motion, and joint stability. The AOFAS scores were compared between fixation and non-fixation groups in each group.

Results: The procedure was successfully completed by all patients in each group, and there was no significant difference in operation time ( =3.677, =0.159). All patients were followed up 12-36 months with a mean time of 16.8 months. At last follow-up, 6 patients were found to have suboptimal ankle planarity, including 2 patients (5.3%) in the type Ⅰ group and 4 patients (13.3%) in the type Ⅱ group, with no significant difference between groups ( =6.566, =0.161). The ankle joints of all the patients in each group showed mild degeneration; the fractures all healed well and no delayed union or nonunion occurred. There was no significant difference in the fracture healing time and full weight-bearing time between groups ( >0.05). No complications such as incision infection, fracture displacement, or plate screw loosening and fracture occurred during follow-up. At last follow-up, the total scores and pain scores of the AOFAS scores in the type Ⅱ group were significantly lower than those in the type Ⅰand Ⅲ groups ( <0.05), there was no significant difference between groups in the scores for the quality of daily life, joint range of motion, and joint stability between groups ( >0.05). There was no significant difference in any of the scores between the unfixed and fixed groups, except for the pain and quality of daily life scores, which were significantly lower ( <0.05) in the unfixed group of type Ⅱ group than the fixed group.

Conclusion: Haraguchi type Ⅱ posterior malleolus fractures have a worse prognosis than types Ⅰ and Ⅲ fractures, especially in terms of postoperative pain, which can be significantly improved by fixing the posterior malleolus; the presence or absence of posterior malleolus fixation in types Ⅰ and Ⅲ has less influence on prognosis.
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http://dx.doi.org/10.7507/1002-1892.202012114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218178PMC
June 2021

Development and Validation of a Nomogram Based on Nutritional Indicators and Tumor Markers for Prognosis Prediction of Pancreatic Ductal Adenocarcinoma.

Front Oncol 2021 31;11:682969. Epub 2021 May 31.

Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.

Purpose: This study aimed to develop and validate a nomogram with preoperative nutritional indicators and tumor markers for predicting prognosis of patients with pancreatic ductal adenocarcinoma (PDAC).

Methods: We performed a bicentric, retrospective study including 155 eligible patients with PDAC. Patients were divided into a training group (n = 95), an internal validation group (n = 34), an external validation group (n = 26), and an entire validation group (n = 60). Cox regression analysis was conducted in the training group to identify independent prognostic factors to construct a nomogram for overall survival (OS) prediction. The performance of the nomogram was assessed in validation groups and through comparison with controlling nutritional status (CONUT) and prognostic nutrition index (PNI).

Results: The least absolute shrinkage and selection operator (LASSO) regression, univariate and multivariate Cox regression analysis revealed that serum albumin and lymphocyte count were independent protective factors while CA19-9 and diabetes were independent risk factors. The concordance index (C-index) of the nomogram in the training, internal validation, external validation and entire validation groups were 0.777, 0.769, 0.759 and 0.774 respectively. The areas under curve (AUC) of the nomogram in each group were 0.861, 0.845, 0.773, and 0.814. C-index and AUC of the nomogram were better than those of CONUT and PNI in the training and validation groups. The net reclassification index (NRI), integrated discrimination improvement (IDI) and decision curve analysis showed improvement of accuracy of the nomogram in predicting OS and better net benefit in guiding clinical decisions in comparison with CONUT and PNI.

Conclusions: The nomogram incorporating four preoperative nutritional and tumor markers including serum albumin concentration, lymphocyte count, CA19-9 and diabetes mellitus could predict the prognosis more accurately than CONUT and PNI and may serve as a clinical decision support tool to determine what treatment options to choose.
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http://dx.doi.org/10.3389/fonc.2021.682969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200845PMC
May 2021

The gut microbiome: implications for neurogenesis and neurological diseases.

Neural Regen Res 2022 Jan;17(1):53-58

Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.

There is an increasing recognition of the strong links between the gut microbiome and the brain, and there is persuasive evidence that the gut microbiome plays a role in a variety of physiological processes in the central nervous system. This review summarizes findings that gut microbial composition alterations are linked to hippocampal neurogenesis, as well as the possible mechanisms of action; the existing literature suggests that microbiota influence neurogenic processes, which can result in neurological disorders. We consider this evidence from the perspectives of neuroinflammation, microbial-derived metabolites, neurotrophins, and neurotransmitters. Based on the existing research, we propose that the administration of probiotics can normalize the gut microbiome. This could therefore also represent a promising treatment strategy to counteract neurological impairment.
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http://dx.doi.org/10.4103/1673-5374.315227DOI Listing
January 2022

A Multi-Phase Based Multi-Application Mapping Approach for Many-Core Networks-on-Chip.

Micromachines (Basel) 2021 May 26;12(6). Epub 2021 May 26.

College of Electronic and Information Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing 211106, China.

More and more attention is being paid to the use of massive parallel computing performed on many-core Networks-on-Chip (NoC) in order to accelerate performance. Simultaneously deploying multiple applications on NoC is one feasible way to achieve this. In this paper, we propose a multi-phase-based multi-application mapping approach for NoC design. Our approach began with a rectangle analysis, which offered several potential regions for application. Then we mapped all tasks of the application into these potential regions using a genetic algorithm, and identified the one which exhibited the strongest performance. When the packeted regions for each application were identified, a B*Tree-based simulated annealing algorithm was used to generate the optimal placement for the multi-application mapping regions. The experiment results show that the proposed approach can achieve a considerable reduction in network power consumption (up to 23.45%) and latency (up to 24.42%) for a given set of applications.
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http://dx.doi.org/10.3390/mi12060613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227643PMC
May 2021

Roles of miR-10a-5p and miR-103a-3p, Regulators of BDNF Expression in Follicular Fluid, in the Outcomes of IVF-ET.

Front Endocrinol (Lausanne) 2021 12;12:637384. Epub 2021 May 12.

Institute of Basic Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, plays critical roles in the physiological process of oocyte mature and IVF outcomes of patients with infertility. However, the regulation of BDNF expression in the microenvironment surrounding the oocyte is still unknown. We initially predicted some microRNA (miRNA) candidates targeting with a series of bioinformatics analysis tools to determine the underlying regulatory mechanisms of BDNF, particularly the effect of miRNAs on BDNF expression. Then, we assessed whether the expression of these 14 selected miRNAs was negatively associated with BDNF expression in follicular fluid (FF) samples obtained from mature (>18 mm) or immature (<15 mm) follicles. Finally, we used the candidate miRNAs, miR-103a-3p and miR-10a-5p, to further investigate the relationship between their expression in FF and the outcomes of infertile patients undergoing IVF-ET treatment. The results of the bioinformatics analysis revealed 14 miRNAs that might directly regulate BDNF expression and might have a close relationship with oocyte development. BDNF was expressed at significantly lower levels in FF from immature follicles than in FF from mature follicles, and only the expression of miR-103a-3p and miR-10a-5p was negatively correlated with BDNF expression in FF. Moreover, in another cohort of 106 infertile women undergoing IVF-ET treatment, miR-103a-3p or miR-10a-5p expression predicted the developmental status of the corresponding oocytes in which high expression of miR-103a-3p or miR-10a-5p resulted in a poor quality of embryo on days 3 and 5 during the IVF-ET treatment. In conclusion, our study is the first to show that miR-103a-3p or miR-10a-5p negatively affects the maturation of oocytes by regulating the expression of BDNF in human FF. Additionally, the expression levels of miR-103a-3p or miR-10a-5p in FF may predict the outcomes of IVF, which are helpful for improving embryo selection and consequently the IVF success rate in the clinic.
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http://dx.doi.org/10.3389/fendo.2021.637384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150000PMC
May 2021
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