Publications by authors named "Zhen Fan"

241 Publications

Mitochondrial-targeting nanoprodrugs to mutually reinforce metabolic inhibition and autophagy for combating resistant cancer.

Biomaterials 2021 Sep 28;278:121168. Epub 2021 Sep 28.

Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University, Shanghai, 200072, China; Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai, 201804, China. Electronic address:

Abnormal energy metabolism is one of the hallmarks of cancer and closely linked to therapy resistance. However, existing metabolic inhibitors suffer from inefficient cell enrichment and therapeutic effects. In this work, we developed an effective strategy to mutually reinforce the metabolic inhibition and autophagy for enhanced tumor killing efficacy and combating resistant cancer. First, mitochondrial homing moiety triphenylphosphonium and metabolic inhibitor lonidamine were grafted onto polylysine. After self-assembly of this functionalized polylysine, ferrocene and glucose oxidase were immobilized to afford additional chemotherapy functions, and the final product was named as FG/T-Nanoprodrug. Effective mitochondrial targeting and metabolic inhibition were observed in resistant cancer cells. In addition, owing to the inhibited metabolism, less glucose is consumed to allow FG/T-Nanoprodrug to produce excess reactive oxygen species (ROS) by glucose oxidase and ferrocene. The enhanced chemodynamic therapy increases the mitochondrial permeability to promote the release of cytochrome c from mitochondria, ultimately induces high levels of autophagy. The FG/T-Nanoprodrug demonstrated superior mutually reinforcing of metabolic inhibition (up to 3.7-fold compared to free lonidamine) and autophagy (up to 125.3-fold compared to free lonidamine) to effectively kill resistant cancer cell both in vitro and in vivo. Overall, this strategy could pave a new way to efficient treatment of resistant cancer and other metabolically abnormal diseases.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121168DOI Listing
September 2021

Bone-Targeting Polymer Vesicles for Effective Therapy of Osteoporosis.

Nano Lett 2021 10 16;21(19):7998-8007. Epub 2021 Sep 16.

Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.

With the aging of the population, postmenopausal osteoporosis becomes increasingly widespread and severe as fractures caused by osteoporosis may lead to permanent disabilities and even death. Inspired by extracellular vesicles that participate in bone remodeling, we present a biomimicking polymer vesicle for bone-targeted β-estradiol (E) delivery. This vesicle is self-assembled from a poly(ε-caprolactone)--poly[(l-glutamic acid)--(l-glutamic acid-alendronic acid)] (PCL--P[Glu--(Glu-ADA)]) diblock copolymer. The alendronic acid (ADA) on the coronas endows the polymer vesicles with a high bone affinity and acts synergistically with E to achieve an enhanced therapeutic effect. As confirmed with ovariectomized osteoporosis rat models, bone loss was significantly reversed as the recovery rates of total BMD (bone mineral density) and trabecular BMD were 70.4% and 99.3%, respectively. Overall, this work provides fresh insight into the treatment of osteoporosis.
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http://dx.doi.org/10.1021/acs.nanolett.1c02150DOI Listing
October 2021

Tilted implantation technique for edentulous patients.

Hua Xi Kou Qiang Yi Xue Za Zhi 2021 Aug;39(4):377-385

Dept. of Implantology, School & Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, China.

The tilted implantation technique is characterized by placing the implant at an angle of more than 15° and less than 45° from the horizontal plane. This technique can avoid damaging the maxillary sinus, inferior alveolar nerve, nasal base, and other anatomical structures when the height of the upper and lower jaw available bone is insufficient, to maximize the use of available bone and avoid a large range of bone increment. The tilted implantation technique can reduce the trauma of the surgery, increase the possibility of immediate restoration and shorten the treatment cycle, which has been widely used clinically. In this review, the scope of application, design elements, design scheme and complications of the tilted implantation technique for edentulous patients will be described.
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http://dx.doi.org/10.7518/hxkq.2021.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381128PMC
August 2021

Nitrogen removal performance and microbiological characteristics of a three-stage series of vertical flow constructed wetlands.

Ying Yong Sheng Tai Xue Bao 2021 Jul;32(7):2578-2588

Anhui Province Key Laboratory of Farmland Ecological Conservation and Pollution Prevention, School of Resources and Environment, Anhui Agricultural University, Hefei 230036, China.

In this study, the treatment performance and underlying molecular mechanisms of nitrogen transformation in a three-stage series of vertical flow constructed wetlands (T-VFCWs) treating rural domestic sewage were investigated at three different hydraulic loading rates (HLRs). Specifi-cally, the T-VFCWs composed of three sequential vertical flow constructed wetlands (termed V-1, V-2 and V-3), which were built according to the topography. The results showed that high pollutant removal rates could be achieved when the T-VFCWs was operated to treat rural domestic sewage, even though the HLR increased from 0.10 to 0.20 m·m·d. Effluent quality of the T-VFCWs could reach Discharge Standard of Pollutants for Municipal Wastewater Treatment Plant (GB 18918-2002) class A standard. Regarding to the T-VFCWs operated under the oxygen-limiting conditions, three different pathways for nitrogen transformation could be respectively formed in V-1, V-2 and V-3, owing to the specific influent quality of each subunit. Consequently, the T-VFCWs were effective in nitrogen removal as a result of the collaboration of the three subunits. When the T-VFCWs ran constantly during the test, nitrogen removal in V-1, V-2, and V-3 respectively relied on the nitritation/denitrification process, the completely autotrophic nitrogen removal over nitrite (CANON) process, and the denitrification process. The contributions of three subunits for total nitrogen (TN) and NH-N removal were (51.3±4.4)% and (63.7±2.6)%, (30.9±4.8)% and (35.5±4.5)%, (17.8±5.0)% and (0.8±0.1)%, respectively. This study could provide scientific basis and technical support for the research and the engineering application of hybrid constructed wetlands.
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http://dx.doi.org/10.13287/j.1001-9332.202107.031DOI Listing
July 2021

Detection of human white matter activation and evaluation of its function in movement decoding using stereo-electroencephalography (SEEG).

J Neural Eng 2021 08 12;18(4). Epub 2021 Aug 12.

State Key Laboratory of Mechanical Systems and Vibrations, Institute of Robotics, Shanghai Jiao Tong University, Shanghai, People's Republic of China.

. White matter tissue takes up approximately 50% of the human brain volume and it is widely known as a messenger conducting information between areas of the central nervous system. However, the characteristics of white matter neural activity and whether white matter neural recordings can contribute to movement decoding are often ignored and still remain largely unknown. In this work, we make quantitative analyses to investigate these two important questions using invasive neural recordings.. We recorded stereo-electroencephalography (SEEG) data from 32 human subjects during a visually-cued motor task, where SEEG recordings can tap into gray and white matter electrical activity simultaneously. Using the proximal tissue density method, we identified the location (i.e. gray or white matter) of each SEEG contact. Focusing on alpha oscillatory and high gamma activities, we compared the activation patterns between gray matter and white matter. Then, we evaluated the performance of such white matter activation in movement decoding.. The results show that white matter also presents activation under the task, in a similar way with the gray matter but at a significantly lower amplitude. Additionally, this work also demonstrates that combing white matter neural activities together with that of gray matter significantly promotes the movement decoding accuracy than using gray matter signals only.. Taking advantage of SEEG recordings from a large number of subjects, we reveal the response characteristics of white matter neural signals under the task and demonstrate its enhancing function in movement decoding. This study highlights the importance of taking white matter activities into consideration in further scientific research and translational applications.
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http://dx.doi.org/10.1088/1741-2552/ac160eDOI Listing
August 2021

LncRNA-encoded microproteins: A new form of cargo in cell culture-derived and circulating extracellular vesicles.

J Extracell Vesicles 2021 Jul 12;10(9):e12123. Epub 2021 Jul 12.

Laboratory of Protein and Peptide Pharmaceuticals and Laboratory of Proteomics Institute of Biophysics Chinese Academy of Sciences Beijing China.

Advancements in omics-based technologies over the past few years have led to the discovery of numerous biologically relevant peptides encoded by small open reading frames (smORFs) embedded in long noncoding RNA (lncRNA) transcripts (referred to as microproteins here) in a variety of species. However, the mechanisms and modes of action that underlie the roles of microproteins have yet to be fully characterized. Herein, we provide the first experimental evidence of abundant microproteins in extracellular vesicles (EVs) derived from glioma cancer cells, indicating that the EV-mediated transfer of microproteins may represent a novel mechanism for intercellular communication. Intriguingly, when examining human plasma, 48, 11 and 3 microproteins were identified from purified EVs, whole plasma and EV-free plasma, respectively, suggesting that circulating microproteins are primarily enriched in EVs. Most importantly, the preliminary data showed that the expression profile of EV microproteins in glioma patient diverged from the health donors, suggesting that the circulating microproteins in EVs might have potential diagnostic application in identifying patients with glioma.
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http://dx.doi.org/10.1002/jev2.12123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275822PMC
July 2021

Astrocyte reactivity with late-onset cognitive impairment assessed in vivo using C-BU99008 PET and its relationship with amyloid load.

Mol Psychiatry 2021 Jul 15. Epub 2021 Jul 15.

Department of Brain Sciences, Imperial College London, London, UK.

C-BU99008 is a novel positron emission tomography (PET) tracer that enables selective imaging of astrocyte reactivity in vivo. To explore astrocyte reactivity associated with Alzheimer's disease, 11 older, cognitively impaired (CI) subjects and 9 age-matched healthy controls (HC) underwent 3T magnetic resonance imaging (MRI), F-florbetaben and C-BU99008 PET. The 8 amyloid (Aβ)-positive CI subjects had higher C-BU99008 uptake relative to HC across the whole brain, but particularly in frontal, temporal, medial temporal and occipital lobes. Biological parametric mapping demonstrated a positive voxel-wise neuroanatomical correlation between C-BU99008 and F-florbetaben. Autoradiography using H-BU99008 with post-mortem Alzheimer's brains confirmed through visual assessment that increased H-BU99008 binding localised with the astrocyte protein glial fibrillary acid protein and was not displaced by PiB or florbetaben. This proof-of-concept study provides direct evidence that C-BU99008 can measure in vivo astrocyte reactivity in people with late-life cognitive impairment and Alzheimer's disease. Our results confirm that increased astrocyte reactivity is found particularly in cortical regions with high Aβ load. Future studies now can explore how clinical expression of disease varies with astrocyte reactivity.
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http://dx.doi.org/10.1038/s41380-021-01193-zDOI Listing
July 2021

Boosting Polarization Switching-Induced Current Injection by Mechanical Force in Ferroelectric Thin Films.

ACS Appl Mater Interfaces 2021 Jun 26;13(22):26180-26186. Epub 2021 May 26.

School of Physics, University College Dublin, Belfield, Dublin D04 V1W8, Ireland.

When scaling the lateral size of a ferroelectric random access memory (FeRAM) device down to the nanometer range, the polarization switching-induced displacement current becomes small and challenging to detect, which greatly limits the storage density of FeRAM. Here, we report the observation of significantly enhanced injection currents, much larger than typical switching currents, induced by polarization switching in BiFeO thin films via conductive atomic force microscopy. Interestingly, this injected current can be effectively modulated by applying mechanical force. As the loading force increases from ∼50 to ∼750 nN, the magnitude of the injected current increases and the critical voltage to trigger the current injection decreases. Notably, changing the loading force by an order of magnitude increases the peak current by 2-3 orders of magnitude. The mechanically boosted injected current could be useful for the development of high-density FeRAM devices. The mechanical modulation of the injected current may be attributed to the mechanical force-induced changes in the barrier height and interfacial layer width.
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http://dx.doi.org/10.1021/acsami.1c04912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289170PMC
June 2021

Genomic Characterization of the Fruity Aroma Gene, , Reveals a Gene Dosage Effect on γ-Decalactone Production in Strawberry ( × ).

Front Plant Sci 2021 4;12:639345. Epub 2021 May 4.

Department of Horticultural Sciences, Institute of Food and Agricultural Sciences (IFAS) Gulf Coast Research and Education Center, University of Florida, Wimauma, FL, United States.

Strawberries produce numerous volatile compounds that contribute to the unique flavors of fruits. Among the many volatiles, γ-decalactone (γ-D) has the greatest contribution to the characteristic fruity aroma in strawberry fruit. The presence or absence of γ-D is controlled by a single locus, . However, this locus has not yet been systematically characterized in the octoploid strawberry genome. It has also been reported that the volatile content greatly varies among the strawberry varieties possessing , suggesting that another genetic factor could be responsible for the different levels of γ-D in fruit. In this study, we explored the genomic structure of and determined the allele dosage of that regulates variations of γ-D production in cultivated octoploid strawberry. The genome-wide association studies confirmed the major locus that regulates the γ-D production in cultivated strawberry. With the hybrid capture-based next-generation sequencing analysis, a major presence-absence variation of was discovered among γ-D producers and non-producers. To explore the genomic structure of in the octoploid strawberry, three bacterial artificial chromosome (BAC) libraries were developed. A deletion of 8,262 bp was consistently found in the region of γ-D non-producing varieties. With the newly developed InDel-based codominant marker genotyping, along with γ-D metabolite profiling data, we revealed the impact of gene dosage effect for the production of γ-D in the octoploid strawberry varieties. Altogether, this study provides systematic information of the prominent role of presence and absence polymorphism in producing γ-D and proposes that both alleles of are required to produce the highest content of fruity aroma in strawberry fruit.
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http://dx.doi.org/10.3389/fpls.2021.639345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129584PMC
May 2021

Self-Related Stimuli Decoding With Auditory and Visual Modalities Using Stereo-Electroencephalography.

Front Neurosci 2021 4;15:653965. Epub 2021 May 4.

State Key Laboratory of Mechanical System and Vibration, School of Mechanical Engineering, Shanghai Jiao Tong University, Shanghai, China.

Name recognition plays important role in self-related cognitive processes and also contributes to a variety of clinical applications, such as autism spectrum disorder diagnosis and consciousness disorder analysis. However, most previous name-related studies usually adopted noninvasive EEG or fMRI recordings, which were limited by low spatial resolution and temporal resolution, respectively, and thus millisecond-level response latencies in precise brain regions could not be measured using these noninvasive recordings. By invasive stereo-electroencephalography (SEEG) recordings that have high resolution in both the spatial and temporal domain, the current study distinguished the neural response to one's own name or a stranger's name, and explored common active brain regions in both auditory and visual modalities. The neural activities were classified using spatiotemporal features of high-gamma, beta, and alpha band. Results showed that different names could be decoded using multi-region SEEG signals, and the best classification performance was achieved at high gamma (60-145 Hz) band. In this case, auditory and visual modality-based name classification accuracies were 84.5 ± 8.3 and 79.9 ± 4.6%, respectively. Additionally, some single regions such as the supramarginal gyrus, middle temporal gyrus, and insula could also achieve remarkable accuracies for both modalities, supporting their roles in the processing of self-related information. The average latency of the difference between the two responses in these precise regions was 354 ± 63 and 285 ± 59 ms in the auditory and visual modality, respectively. This study suggested that name recognition was attributed to a distributed brain network, and the subsets with decoding capabilities might be potential implanted regions for awareness detection and cognition evaluation.
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http://dx.doi.org/10.3389/fnins.2021.653965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129191PMC
May 2021

Corrigendum to "Type 2 diabetes-induced overactivation of P300 contributes to skeletal muscle atrophy by inhibiting autophagic flux" [Life Sci. 2020 Oct 1;258:118243].

Life Sci 2021 Aug 11;279:119589. Epub 2021 May 11.

Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Youyi Road 1, Chongqing 400042, China. Electronic address:

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http://dx.doi.org/10.1016/j.lfs.2021.119589DOI Listing
August 2021

Enhancement of ferroelectricity and homogeneity of orthorhombic phase in HfZrOthin films.

Nanotechnology 2021 May 26;32(33). Epub 2021 May 26.

Guangdong Provincial Key Laboratory of Quantum Engineering and Quantum Materials and Institute for Advanced Materials, South China Academy of Advanced Optoelectronics, South China Normal University, Guangzhou 510006, People's Republic of China.

By adoption of a high permittivity ZrOcapping layer (ZOCL), enhanced ferroelectric properties were achieved in the HfZrO(HZO) thin films. For HZO thin film with 10 Å ZOCL, the 2value can reach as high as ∼43.1C cmunder a sweep electric field of 3 MV cm. In addition, a reduced coercive field of 1.5 MV cmwas observed, which is comparable to that of HZO with metallic CL. Furthermore, the homogeneity of ferroelectric orthorhombic phase in HZO films was observed to be clearly increased, as evidenced by nanoscale piezoelectric force microscopy measurements. These results demonstrate that ZOCL is very favorable for high performance ferroelectric HZO films and their future device applications.
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http://dx.doi.org/10.1088/1361-6528/abfc70DOI Listing
May 2021

Nanoscale Ferroelectric Characterization with Heterodyne Megasonic Piezoresponse Force Microscopy.

Adv Sci (Weinh) 2021 Apr 15;8(8):2003993. Epub 2021 Feb 15.

Department of Mechanical Engineering National University of Singapore Singapore 117576 Singapore.

Piezoresponse force microscopy (PFM), as a powerful nanoscale characterization technique, has been extensively utilized to elucidate diverse underlying physics of ferroelectricity. However, intensive studies of conventional PFM have revealed a growing number of concerns and limitations which are largely challenging its validity and applications. In this study, an advanced PFM technique is reported, namely heterodyne megasonic piezoresponse force microscopy (HM-PFM), which uses 10 to 10 Hz high-frequency excitation and heterodyne method to measure the piezoelectric strain at nanoscale. It is found that HM-PFM can unambiguously provide standard ferroelectric domain and hysteresis loop measurements, and an effective domain characterization with excitation frequency up to ≈110 MHz is demonstrated. Most importantly, owing to the high-frequency and heterodyne scheme, the contributions from both electrostatic force and electrochemical strain can be significantly minimized in HM-PFM. Furthermore, a special measurement of difference-frequency piezoresponse frequency spectrum (DFPFS) is developed on HM-PFM and a distinct DFPFS characteristic is observed on the materials with piezoelectricity. By performing DFPFS measurement, a truly existed but very weak electromechanical coupling in CHNHPbI perovskite is revealed. It is believed that HM-PFM can be an excellent candidate for the ferroelectric or piezoelectric studies where conventional PFM results are highly controversial.
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http://dx.doi.org/10.1002/advs.202003993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061351PMC
April 2021

Reorganization of auditory-visual network interactions in long-term unilateral postlingual hearing loss.

J Clin Neurosci 2021 May 19;87:97-102. Epub 2021 Mar 19.

Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, China; Neurosurgical Institute of Fudan University, China; Shanghai Clinical Medical Center of Neurosurgery, China. Electronic address:

Long-term unilateral hearing loss could reorganize the functional network association between the bilateral auditory cortices, while alterations of other functional networks need to be further explored. We attempted to investigate the pattern of the reorganization of functional network associations between the auditory and visual cortex caused by long-term postlingual unilateral hearing loss (UHI) and its relationship with clinical characteristics. Therefore, 48 patients with hearing loss caused by unilateral acoustic tumors and 52 matched healthy controls were enrolled, and their high-resolution structural MRI and resting-state functional MRI data were also collected to depict the brain network. Degree centrality (DC) was employed to evaluate the functional network association of the auditory-visual network interaction. Group comparisons were performed to investigate the network reorganization, and its correlations with clinical data were calculated. Compared with the healthy control group, patients with UHI showed significantly increased DC between the auditory network (superior temporal gyrus and the medial geniculate body) and the visual network. Meanwhile, this difference was positively correlated with the extent of hearing impairment, and the correlation was more significant with the ipsilateral superior temporal gyrus in cases of acoustic neuroma. These results suggest that long-term unilateral hearing impairment may lead to enhancement of the visual-auditory network interactions and that the degree of reorganization is positively correlated with the pure tone average (PTA) and is more significant for the ipsilateral superior temporal gyrus, which provides clinical evidence regarding cross-modal plasticity in the UHI and its lateralization.
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http://dx.doi.org/10.1016/j.jocn.2021.02.017DOI Listing
May 2021

Volatiles Influencing Sensory Attributes and Bayesian Modeling of the Soluble Solids-Sweetness Relationship in Strawberry.

Front Plant Sci 2021 17;12:640704. Epub 2021 Mar 17.

Horticultural Sciences Department, IFAS Gulf Coast Research and Education Center, University of Florida, Wimauma, FL, United States.

Descriptive analysis trained sensory panels has great power to facilitate flavor improvement in fresh fruits and vegetables. When paired with an understanding of fruit volatile organic compounds, descriptive analysis can help uncover the chemical drivers of sensory attributes. In the present study, 213 strawberry samples representing 56 cultivars and advanced selections were sampled over seven seasons and subjected to both sensory descriptive and chemical analyses. Principal component analysis and K-cluster analyses of sensory data highlighted three groups of strawberry samples, with one classified as superior with high sweetness and strawberry flavor and low sourness and green flavor. Partial least square models revealed 20 sweetness-enhancing volatile organic compounds and two sweetness-reducing volatiles, many of which overlap with previous consumer sensory studies. Volatiles modulating green, sour, astringent, overripe, woody, and strawberry flavors were also identified. The relationship between soluble solids content (SSC) and sweetness was modeled with Bayesian regression, generating probabilities for sweetness levels from varying levels of soluble solids. A hierarchical Bayesian model with month effects indicated that SSC is most correlated to sweetness toward the end of the fruiting season, making this the best period to make phenotypic selections for soluble solids. Comparing effects from genotypes, harvest months, and their interactions on sensory attributes revealed that sweetness, sourness, and firmness were largely controlled by genetics. These findings help formulate a paradigm for improvement of eating quality in which sensory analyses drive the targeting of chemicals important to consumer-desired attributes, which further drive the development of genetic tools for improvement of flavor.
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http://dx.doi.org/10.3389/fpls.2021.640704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010315PMC
March 2021

Strawberry sweetness and consumer preference are enhanced by specific volatile compounds.

Hortic Res 2021 Apr 1;8(1):66. Epub 2021 Apr 1.

Horticultural Sciences Department, University of Florida, IFAS Gulf Coast Research and Education Center, Wimauma, FL, USA.

Breeding crops for improved flavor is challenging due to the high cost of sensory evaluation and the difficulty of connecting sensory experience to chemical composition. The main goal of this study was to identify the chemical drivers of sweetness and consumer liking for fresh strawberries (Fragaria × ananassa). Fruit of 148 strawberry samples from cultivars and breeding selections were grown and harvested over seven years and were subjected to both sensory and chemical analyses. Each panel consisted of at least 100 consumers, resulting in more than 15,000 sensory data points per descriptor. Three sugars, two acids and 113 volatile compounds were quantified. Consumer liking was highly associated with sweetness intensity, texture liking, and flavor intensity, but not sourness intensity. Partial least square analyses revealed 20 volatile compounds that increased sweetness perception independently of sugars; 18 volatiles that increased liking independently of sugars; and 15 volatile compounds that had positive effects on both. Machine learning-based predictive models including sugars, acids, and volatiles explained at least 25% more variation in sweetness and liking than models accounting for sugars and acids only. Volatile compounds such as γ-dodecalactone; 5-hepten-2-one, 6-methyl; and multiple medium-chain fatty acid esters may serve as targets for breeding or quality control attributes for strawberry products. A genetic association study identified two loci controlling ester production, both on linkage group 6 A. Co-segregating makers in these regions can be used for increasing multiple esters simultaneously. This study demonstrates a paradigm for improvement of fruit sweetness and flavor in which consumers drive the identification of the most important chemical targets, which in turn drives the discovery of genetic targets for marker-assisted breeding.
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http://dx.doi.org/10.1038/s41438-021-00502-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012349PMC
April 2021

Newcastle Disease Virus Entry into Chicken Macrophages via a pH-Dependent, Dynamin and Caveola-Mediated Endocytic Pathway That Requires Rab5.

J Virol 2021 06 10;95(13):e0228820. Epub 2021 Jun 10.

Division of Avian Infectious Diseases, the State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People's Republic of China.

The cellular entry pathways and the mechanisms of Newcastle disease virus (NDV) entry into cells are poorly characterized. In this study, we demonstrated that chicken interferon-induced transmembrane protein 1 (chIFITM1), which is located in the early endosomes, could limit the replication of NDV in chicken macrophage cell line HD11, suggesting the endocytic entry of NDV into chicken macrophages. Then, we presented a systematic study about the entry mechanism of NDV into chicken macrophages. First, we demonstrated that a low-pH condition and dynamin were required during NDV entry. However, NDV entry into chicken macrophages was independent of clathrin-mediated endocytosis. We also found that NDV entry was dependent on membrane cholesterol. The NDV entry and replication were significantly reduced by nystatin and phorbol 12-myristate 13-acetate treatment, overexpression of dominant-negative (DN) caveolin-1, or knockdown of caveolin-1, suggesting that NDV entry depends on caveola-mediated endocytosis. However, macropinocytosis did not play a role in NDV entry into chicken macrophages. In addition, we found that Rab5, rather than Rab7, was involved in the entry and traffic of NDV. The colocalization of NDV with Rab5 and early endosome suggested that NDV virion was transported to early endosomes in a Rab5-dependent manner after internalization. Of particular note, the caveola-mediated endocytosis was also utilized by NDV to enter primary chicken macrophages. Moreover, NDV entered different cell types using different pathways. Collectively, our findings demonstrate for the first time that NDV virion enters chicken macrophages via a pH-dependent, dynamin and caveola-mediated endocytosis pathway and that Rab5 is involved in the traffic and location of NDV. Although the pathogenesis of Newcastle disease virus (NDV) has been extensively studied, the detailed mechanism of NDV entry into host cells is largely unknown. Macrophages are the first-line defenders of host defense against infection of pathogens. Chicken macrophages are considered one of the main types of target cells during NDV infection. Here, we comprehensively investigated the entry mechanism of NDV in chicken macrophages. This is the first report to demonstrate that NDV enters chicken macrophages via a pH-dependent, dynamin and caveola-mediated endocytosis pathway that requires Rab5. The result is important for our understanding of the entry of NDV in chicken macrophages, which will further advance the knowledge of NDV pathogenesis and provide useful clues for the development of novel preventive or therapeutic strategies against NDV infection. In addition, this information will contribute to our further understanding of pathogenesis with regard to other members of the genus in the family.
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http://dx.doi.org/10.1128/JVI.02288-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437353PMC
June 2021

FGF19 protects skeletal muscle against obesity-induced muscle atrophy, metabolic derangement and abnormal irisin levels via the AMPK/SIRT-1/PGC-α pathway.

J Cell Mol Med 2021 04 10;25(7):3585-3600. Epub 2021 Mar 10.

Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Obesity is associated with biological dysfunction in skeletal muscle. As a condition of obesity accompanied by muscle mass loss and physical dysfunction, sarcopenic obesity (SO) has become a novel public health problem. Human fibroblast growth factor 19 (FGF19) plays a therapeutic role in metabolic diseases. However, the protective effects of FGF19 on skeletal muscle in obesity and SO are still not completely understood. Our results showed that FGF19 administration improved muscle loss and grip strength in young and aged mice fed a high-fat diet (HFD). Increases in muscle atrophy markers (FOXO-3, Atrogin-1, MuRF-1) were abrogated by FGF19 in palmitic acid (PA)-treated C2C12 myotubes and in the skeletal muscle of HFD-fed mice. FGF19 not only reduced HFD-induced body weight gain, excessive lipid accumulation and hyperlipidaemia but also promoted energy expenditure (PGC-1α, UCP-1, PPAR-γ) in brown adipose tissue (BAT). FGF19 treatment restored PA- and HFD-induced hyperglycaemia, impaired glucose tolerance and insulin resistance (IRS-1, GLUT-4) and mitigated the PA- and HFD-induced decrease in FNDC-5/irisin expression. However, these beneficial effects of FGF19 on skeletal muscle were abolished by inhibiting AMPK, SIRT-1 and PGC-1α expression. Taken together, this study suggests that FGF19 protects skeletal muscle against obesity-induced muscle atrophy, metabolic derangement and abnormal irisin secretion partially through the AMPK/SIRT-1/PGC-α signalling pathway, which might be a potential therapeutic target for obesity and SO.
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http://dx.doi.org/10.1111/jcmm.16448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034456PMC
April 2021

Quasi-one-dimensional metallic conduction channels in exotic ferroelectric topological defects.

Nat Commun 2021 Feb 26;12(1):1306. Epub 2021 Feb 26.

Guangdong Provincial Key Laboratory of Quantum Engineering and Quantum Materials, Institute for Advanced Materials, South China Academy of Advanced Optoelectronics, South China Normal University, Guangzhou, China.

Ferroelectric topological objects provide a fertile ground for exploring emerging physical properties that could potentially be utilized in future nanoelectronic devices. Here, we demonstrate quasi-one-dimensional metallic high conduction channels associated with the topological cores of quadrant vortex domain and center domain (monopole-like) states confined in high quality BiFeO nanoislands, abbreviated as the vortex core and the center core. We unveil via the phase-field simulation that the superfine metallic conduction channels along the center cores arise from the screening charge carriers confined at the core region, whereas the high conductance of vortex cores results from a field-induced twisted state. These conducting channels can be reversibly created and deleted by manipulating the two topological states via electric field, leading to an apparent electroresistance effect with an on/off ratio higher than 10. These results open up the possibility of utilizing these functional one-dimensional topological objects in high-density nanoelectronic devices, e.g. nonvolatile memory.
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http://dx.doi.org/10.1038/s41467-021-21521-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910570PMC
February 2021

Inhibition of soluble epoxide hydrolase (sEH) protects hippocampal neurons and reduces cognitive decline in type 2 diabetic mice.

Eur J Neurosci 2021 04 22;53(8):2532-2540. Epub 2021 Mar 22.

Department of Geriatrics, First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Diabetes mellitus is a metabolic disorder that can lead to cognitive dysfunction. The hippocampus plays an important role in the cognitive function. Research has identified correlations between hippocampal impairment and diabetes, yet their intermediate remains unclear. Soluble epoxide hydrolase (sEH) is an enzyme that degrades epoxyeicosatrienoic acids (EETs), which have multiple protective effects by suppressing inflammation, apoptosis and oxidative stress. In this study, under diabetic conditions both hippocampal injury and cognitive decline are accompanied by upregulation of sEH. Moreover, the sEH inhibitor trans-4-[4-(3-adamantan-1-y1-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB) prevents cognitive dysfunction and decreased ROS accumulation and apoptosis in the diabetic hippocampus. t-AUCB treatment restored neuronal synaptic plasticity by restoring the expression of the postsynaptic proteins Postsynaptic density protein-95 (PSD95) and N-methyl-d-aspartate receptor subunit 2B (NR2B), the levels of which were positively correlated with Proline-rich tyrosine kinase 2 (Pyk2) levels under diabetic conditions. Thus, we suggest that hippocampal protection via sEH inhibition might be a potential therapeutic approach to attenuate the progression of cognitive decline in diabetes.
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http://dx.doi.org/10.1111/ejn.15150DOI Listing
April 2021

The protective role of Ephrin-B2/EphB4 signaling in osteogenic differentiation under inflammatory environment.

Exp Cell Res 2021 03 29;400(2):112505. Epub 2021 Jan 29.

Department of Prosthodontics, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, No.639 Zhizaoju Road, Shanghai, 200011, China; National Clinical Research Center for Oral Diseases, No.639 Zhizaoju Road, Shanghai, 200011, China; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, No.639 Zhizaoju Road, Shanghai, 200011, China. Electronic address:

Inflammation and alveolar bone destruction constitute the main pathological process of periodontitis. However, the molecular mechanisms of bone destruction under the inflammation environment remain unclear. This study aims to explore the role of Ephrin-B2/EphB4 signaling in osteogenic differentiation under the inflammation environment. Mouse pre-osteoblasts MC3T3-E1 were pretreated with lipopolysaccharide of Porphyromonas gingivalis (Pg-LPS). The Ephrin-B2/EphB4 signaling was activated, and the osteogenic differentiation of cells was examined. The results showed that activation of Ephrin-B2/EphB4 signaling promoted the expression levels of osteogenic differentiation-related genes, and also relieved the inhibitory effect of Pg-LPS on osteogenesis. Noticeably, the effect of Ephrin-B2/EphB4 signaling might be related to the mitogen-activated protein kinase (MAPK) pathway. While applying Ephrin-B2-Fc and EphB4-Fc to periodontitis mice, we observed the reduction of alveolar crest destruction. The current study revealed the possible role of Ephrin-B2/EphB4 signaling in reducing bone destruction in periodontitis and suggested its potential values for further research.
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http://dx.doi.org/10.1016/j.yexcr.2021.112505DOI Listing
March 2021

Self-Assembled Peptide Nanofibers with Voltage-Regulated Inverse Photoconductance.

ACS Appl Mater Interfaces 2021 Jan 30;13(1):1057-1064. Epub 2020 Dec 30.

State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016, China.

Inverse photoconductance is an uncommon phenomenon observed in selective low-dimensional materials, in which the electrical conductivity of the materials decreases under light illumination. The unique material property holds great promise for biomedical applications in photodetectors, photoelectric logic gates, and low-power nonvolatile memory, which remains a daunting challenge. Especially, tunable photoconductivity for biocompatible materials is highly desired for interfacing with biological systems but is less explored in organic materials. Here, we report nanofibers self-assembled with cyclo-tyrosine-tyrosine (cyclo-YY) having voltage-regulated inverse photoconductance and photoconductance. The peptide nanofibers can be switched back and forth by a bias voltage for imitating biological sensing in artificial vision and memory devices. A peptide optoelectronic resistive random access memory (PORRAM) device has also been fabricated using the nanofibers that can be electrically switched between long-term and short-term memory. The underlying mechanism of the reversible photoconductance is discussed in this paper. Due to the inherent biocompatibility of peptide materials, the reversible photoconductive nanofibers may have broad applications in sensing and storage for biotic and abiotic interfaces.
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http://dx.doi.org/10.1021/acsami.0c18893DOI Listing
January 2021

MitoQ protects against high glucose-induced brain microvascular endothelial cells injury via the Nrf2/HO-1 pathway.

J Pharmacol Sci 2021 Jan 30;145(1):105-114. Epub 2020 Oct 30.

Department of Neurology, The General Hospital of Western Theater Command, Chendu, Sichuan, China. Electronic address:

Brain microvascular endothelial cells (BMECs) dysfunction is related to the pathogenesis of neurovascular complication of diabetes mellitus that adversely lead to various CNS disorders. Mitoquinone (MitoQ) is a mitochondria targeted antioxidant that exerts multiple protective effects in many oxidative damage-related diseases. In this study, we determined the protective effects of MitoQ on high glucose (HG)-induced BMECs injury and investigated the underlying mechanism. We found that HG significantly reduced the expression of Nrf2 and HO-1, decreased mitochondrial membrane potential, increased intracellular and mitochondrial reactive oxygen species (ROS) generation, induced cytoskeletal damage and apoptosis in BMECs. In addition, Mito tempol, a mitochondrial ROS scavenger, significantly reduced HG-induced mitochondrial ROS production and attenuated cytoskeletal damage and cell apoptosis, suggesting MtROS production was involved in HG-induced BMECs injury. Moreover, we found that MitoQ treatment significantly upregulated the expression of Nrf2 and HO-1 in HG-induced BMECs, which is accompanied by improved mitochondrial membrane potential and decreased MtROS production. Meanwhile, MitoQ treatment also remarkably attenuated HG-induced cytoskeletal damage and cell apoptosis in BMECs. However, inhibitor of Nrf2 with ML385 impaired the protective effects of MitoQ in HG-induced BMECs. In conclusion, our results suggest that MitoQ exerts protective effect on HG-induced BMECs injury via activating Nrf2/HO-1 pathway.
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http://dx.doi.org/10.1016/j.jphs.2020.10.007DOI Listing
January 2021

Highly Controllable and Silicon-Compatible Ferroelectric Photovoltaic Synapses for Neuromorphic Computing.

iScience 2020 Dec 30;23(12):101874. Epub 2020 Nov 30.

Institute for Advanced Materials, South China Academy of Advanced Optoelectronics, South China Normal University, Guangzhou 510006, China.

Ferroelectric synapses using polarization switching (a purely electronic switching process) to induce analog conductance change have attracted considerable interest. Here, we propose ferroelectric photovoltaic (FePV) synapses that use polarization-controlled photocurrent as the readout and thus have no limitations on the forms and thicknesses of the constituent ferroelectric and electrode materials. This not only makes FePV synapses easy to fabricate but also reduces the depolarization effect and hence enhances the polarization controllability. As a proof-of-concept implementation, a Pt/Pb(ZrTi)O/LaNiO FePV synapse is facilely grown on a silicon substrate, which demonstrates continuous photovoltaic response modulation with good controllability (small nonlinearity and write noise) enabled by gradual polarization switching. Using photovoltaic response as synaptic weight, this device exhibits versatile synaptic functions including long-term potentiation/depression and spike-timing-dependent plasticity. A simulated FePV synapse-based neural network achieves high accuracies (>93%) for image recognition. This study paves a new way toward highly controllable and silicon-compatible synapses for neuromorphic computing.
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http://dx.doi.org/10.1016/j.isci.2020.101874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736912PMC
December 2020

The Effect of miR-361-3p Targeting TRAF6 on Apoptosis of Multiple Myeloma Cells.

J Microbiol Biotechnol 2021 Feb;31(2):197-206

Department of Hematology, The First People's Hospital of Jingmen, No. 67 Xiangshan Avenue, Jingmen, Hubei Province 448000, P.R. China.

microRNA-361-3p (miR-361-3p) is involved in the carcinogenesis of oral cancer and pancreatic catheter adenocarcinoma, and has anti-carcinogenic effects on non-small cell lung cancer (NSCLC). However, its effect on multiple myeloma (MM) is less reported. Here, we found that upregulating the expression of miR-361-3p inhibited MM cell viability and promoted MM apoptosis. We measured expressions of tumor necrosis factor receptor-associated factor 6 (TRAF6) and miR-361-3p in MM cells and detected the viability, colony formation rate, and apoptosis of MM cells. In addition, we measured expressions of apoptosis-related genes Bcl-2, Bax, and Cleaved caspase-3 (C caspase-3). The binding site between miR-361-3p and TRAF6 was predicted by TargetScan. Our results showed that miR-361-3p was low expressed in the plasma of MM patients and cell lines, while its overexpression inhibited viability and colony formation of MM cells and increased the cell apoptosis. Furthermore, TRAF6, which was predicted to be a target gene of miR-361-3p, was highexpressed in the plasma of patients and cell lines with MM. Rescue experiments demonstrated that the effect of TRAF6 on MM cells was opposite to that of miR-361-3p. Upregulation of miR-361-3p induced apoptosis and inhibited the proliferation of MM cells through targeting TRAF6, suggesting that miR-361-3p might be a potential target for MM therapy.
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http://dx.doi.org/10.4014/jmb.2010.10059DOI Listing
February 2021

Quantitative analysis of cerebellar lobule morphology and clinical cognitive correlates in refractory temporal lobe epilepsy patients.

Epilepsy Behav 2021 01 28;114(Pt A):107553. Epub 2020 Nov 28.

Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China; Neurosurgical Institute of Fudan University, Shanghai, China; Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China.

Purpose: This study was conducted to explore the cerebellar substructure volumetric alterations in refractory unilateral temporal lobe epilepsy (TLE) patients and the relationship with clinical factors and cognitive scores.

Methods: A total of 48 unilateral refractory TLE patients and 48 age- and gender-matched normal controls (NCs) were retrospectively studied. All subjects underwent high-resolution magnetic resonance imaging (MRI) and automatically segmented volumetric brain information was obtained using volBrain and Data Processing Assistant for Resting-State fMRI (DPARSF) separately. Clinical seizure features and cognitive scores were acquired by a structured review of medical records.

Results: The total volumes (TVs) of bilateral crus I, crus II, and IX were significantly smaller in the refractory unilateral TLE epilepsy patients. The gray matter volumes (GMVs) of cerebellar lobules showed lateralized reduction in ipsilateral III, IX, and contralateral crus II. Contralateral crus II GMV showed significant negative correlation with the duration of epilepsy (r = -0.31, p = 0.035) and positive association with the cognitive scores including long-term memory (LTM) (r = 0.39, p = 0.017), short-term memory (STM) (r = 0.51, p = 0.001) verbal comprehension index (VCI) (r = 0.37, p = 0.024), and perceptual organization index (POI) (r = 0.36, p = 0.030). The voxel-based morphometry (VBM) analysis proved similar results. The contralateral crus I GMV was significantly smaller in the generalized onset group (t = 2.536, p = 0.015).

Conclusions: The lobules of the cerebellar in refractory TLE patients manifest different volumetric change characteristics. Crus II contralateral GMV is negatively correlated with the duration of epilepsy and positively associated with the cognitive scores.
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http://dx.doi.org/10.1016/j.yebeh.2020.107553DOI Listing
January 2021

Bone-targeting polymer vesicles for simultaneous imaging and effective malignant bone tumor treatment.

Biomaterials 2021 02 27;269:120345. Epub 2020 Aug 27.

Department of Orthopedics, Shanghai Institute of Bone Tumor, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China; Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, Shanghai, 201804, China. Electronic address:

We present a bone-targeting polymer vesicle with excellent single photon emission computed tomography/computed tomography (SPECT/CT) imaging capability and high antitumor drug delivery efficiency as an integrated platform for the simultaneous diagnosing and treatment of malignant bone tumors. This polymer vesicle can be self-assembled from poly(ε-caprolactone)-b-poly[(L-glutamic acid)-stat-(L-glutamic acid-alendronic acid)] (PCL-b-P[Glu-stat-(Glu-ADA)]), directly in water without the aid of a cosolvent. SPECT/CT dynamically tracked the drug distribution in the bone tumor rabbit models, and the tumor size was significantly reduced from >2.0 cm to <0.6 cm over 11 days. The pathological analysis demonstrated obvious necrosis and apoptosis of the tumor cells. Overall, this bone-targeting polymer vesicle provides us with a new platform for the combination of real-time diagnosis and therapy of malignant bone tumors.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120345DOI Listing
February 2021

Responses of soil bacteria and fungal communities to pristine and sulfidized zinc oxide nanoparticles relative to Zn ions.

J Hazard Mater 2021 03 25;405:124258. Epub 2020 Oct 25.

State Key Laboratory of Crop Stress Biology in Arid Areas, College of Life Sciences, Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, Northwest A&F University, Yangling 712100, Shaanxi, PR China. Electronic address:

Zinc oxide nanoparticles (ZnO NPs) are attracting much interest due to their potential toxicity and ubiquity in consumer products. However, understanding of pristine and transformed ZnO NPs impact on soil microbial communities is still limited. Here, we explored changes in the microbial communities of soils treated with pristine and sulfidized ZnO NPs (s-ZnO NPs), and their corresponding Zn ions (ZnSO) for 30 and 90 days exposures at 100 and 500 mg Zn kg. The similarity in bacterial community responses was observed between ZnO NPs and s-ZnO NPs, and these Zn treatments significantly affected the bacterial communities at 90 days, which exhibited distinct patterns compared to ZnSO. The single-time tested DTPA and HO extractable Zn ions could not fully explain the observed ZnO NPs and s-ZnO NPs impact on bacterial communities. The two most dominant phylum Nitrospirae and Actinobacteria, associated with the reduction of NH-N and dissolved organic carbon, demonstrated significant changes in soils exposed to ZnO NPs and s-ZnO NPs. This suggests the potential long-term impact of transformed ZnO NPs on soil carbon and nitrogen cycling. For fungal communities, we did not find the distinct response patterns of fungal communities between nanoparticulate and ionic Zn exposures.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124258DOI Listing
March 2021

Diagnosis and surgical treatment of non-lesional temporal lobe epilepsy with unilateral amygdala enlargement.

Neurol Sci 2021 Jun 12;42(6):2353-2361. Epub 2020 Oct 12.

Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, No. 12 Mid Wulumuqi Rd, Shanghai, 200040, China.

Objective: Exploring the role of amygdala enlargement (AE) in temporal lobe epilepsy (TLE) without ipsilateral mesial temporal sclerosis (MTS) using comprehensive presurgical workup tools including traditional tools, automatically volumetric analysis, high-density EEG (HD-EEG) source imaging (HD-ESI), and stereoelectroencephalography (SEEG).

Methods: Nine patients diagnosed with TLE-AE who underwent resective surgeries encompassing the amygdala were retrospectively studied. HD-ESI was obtained using 256-channel HD-EEG on the individualized head model. For automatic volumetric analysis, 48 matched controls were enrolled. Diagnosis and surgical strategies were based on a comprehensive workup following the anatomo-electro-clinical principle.

Results: At post-operative follow-up (average 30.9 months), eight patients had achieved Engel class I and one Engel class II recovery. HD-ESI yielded unifocal source estimates in anterior mesial temporal region in 85.7% of cases. Automatic volumetric analysis showed the AE sides were consistent with the values determined through other preoperative workup tools. Furthermore, the amygdala volume of the affected sides in AE was significantly greater than that of the larger sides in controls (p < 0.001). Meanwhile, the amygdala volume lateral index (LI) of AE was significantly higher than in controls (p < 0.001). SEEG analysis showed that ictal onsets arose from the enlarged amygdala (and hippocampus) in all cases.

Conclusion: In addition to traditional workup tools, automatic volumetric analysis, HD-ESI on individualized head model, and invasive SEEG can provide evidence of epileptogenicity in TLE-AE. Resective surgical strategies encompassing the amygdala result in better prognosis. In suspected TLE cases, more attention should be focused on detecting enlargement of amygdala which sometimes is "hidden" in "MR-negative" non-MTS cases.
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http://dx.doi.org/10.1007/s10072-020-04794-8DOI Listing
June 2021
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