Publications by authors named "Wen Li"

2,983 Publications

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The m6A mRNA demethylase FTO in granulosa cells retards FOS-dependent ovarian aging.

Cell Death Dis 2021 Jul 27;12(8):744. Epub 2021 Jul 27.

Center for Reproductive Medicine & Fertility Preservation program, International Peace maternity and Child health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China.

Multifunctional N6-methyladenosine (m6A) has been revealed to be an important epigenetic component in various physiological and pathological processes, but its role in female ovarian aging remains unclear. Thus, we demonstrated m6A demethylase FTO downregulation and the ensuing increased m6A in granulosa cells (GCs) of human aged ovaries, while FTO-knockdown GCs showed faster aging-related phenotypes mediated. Using the m6A-RNA-sequence technique (m6A-seq), increased m6A was found in the FOS-mRNA-3'UTR, which is suggested to be an erasing target of FTO that slows the degradation of FOS-mRNA to upregulate FOS expression in GCs, eventually resulting in GC-mediated ovarian aging. FTO acts as a senescence-retarding protein via m6A, and FOS knockdown significantly alleviates the aging of FTO-knockdown GCs. Altogether, the abovementioned results indicate that FTO in GCs retards FOS-dependent ovarian aging, which is a potential diagnostic and therapeutic target against ovarian aging and age-related reproductive diseases.
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http://dx.doi.org/10.1038/s41419-021-04016-9DOI Listing
July 2021

Silencing of ATG4D suppressed proliferation and enhanced cisplatin-induced apoptosis in hepatocellular carcinoma through Akt/Caspase-3 pathway.

Mol Cell Biochem 2021 Jul 27. Epub 2021 Jul 27.

Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330000, China.

ATG4D, a member of autophagy-related protein 4 (ATG4) family, plays an interplay role between autophagy and apoptosis in cancers. However, the role of ATG4D in hepatocellular carcinoma (HCC) has not been defined. Herein, this study aimed to investigate the role and the underlying mechanism of ATG4D in regulating HCC cell apoptosis. ATG4D was silenced in MHCC-97L HCC cells, and then cell proliferation and apoptosis were examined. ATG4D expression was significantly upregulated in HCC tissues when compared with paired non-tumor tissues. In vitro assays revealed that silencing of ATG4D significantly suppressed cell proliferation, promoted cell apoptosis, and enhanced sensitivity to cisplatin of MHCC-97L cells. Furthermore, silencing of ATG4D decreased the phosphorylation of Akt and increased the protein level of caspase-3. Taken together, ATG4D may play an oncogenic role in HCC progression. These findings suggest that ATG4D may serve as a therapeutic target for HCC therapy.
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http://dx.doi.org/10.1007/s11010-021-04224-zDOI Listing
July 2021

The power and the promise of circRNAs for cancer precision medicine with functional diagnostics and prognostic prediction.

Carcinogenesis 2021 Jul 27. Epub 2021 Jul 27.

National Engineering Laboratory for Deep Process of Rice and Byproducts, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, Hunan, China.

Circular RNA (circRNA) is a large class of covalently closed circular RNA. As a member of competitive endogenous RNA (ceRNA), it participates in the regulation of circRNA-miRNA-mRNA network and plays an important role in the regulation of physiology and pathology. CircRNA is produced by the reverse splicing of exon, intron or both, forming exon or intron circRNA. Studies have shown that circRNA is a ubiquitous molecule, which exceeds the linear mRNA distributed in human cells. Because of its covalent closed-loop structure, circRNA is resistant to RNase R, which is more stable than linear mRNA; circRNA is highly conserved in different species. It was found that circRNA competitively adsorbs miRNA, as a miRNA sponge, to involve in the expression regulation of a variety of genes and plays an important role in tumor development, invasion, metastasis and other processes. These molecules offer new potential opportunities for therapeutic intervention and serve as biomarkers for diagnosis. In this paper, the origin, characteristics and functions of circRNA and its role in tumor development, invasion and metastasis, diagnosis and prognosis are reviewed.
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http://dx.doi.org/10.1093/carcin/bgab071DOI Listing
July 2021

Cascade catalytic nanoplatform based on ions interference strategy for calcium overload therapy and ferroptosis.

Int J Pharm 2021 Jul 23:120937. Epub 2021 Jul 23.

College of Pharmacy, Xinxiang Medical University, Xinxiang 453003, China. Electronic address:

Intracellular ions played prominent part in cell function and behavior. Disrupting intracellular ions homeostasis might switch ions signal from "regulating" to "destroying". Inspired by this, we introduced the ions interference strategy for tumor therapy. Herein, curcumin (CUR) and transferrin (Tf) co-loaded calcium peroxide nanoparticles (CaO NPs) were formulated. With tumor targeting ability, CaO/Tf/CUR pinpointed tumor cells and then instantaneously decomposed in acidic lysosomes, concurrently accompanying with the release of Ca and CUR, as well as the production of HO. Then HO not only damaged structure of Tf to release Fe, but also was converted to hydroxyl radicals via ferric ions mediated Fenton reaction for ferroptosis. In addition, the released Ca and CUR induced Ca overload via exogenous and endogenous calcium ions accumulation, respectively, further activating mitochondria apoptosis signaling pathway for cell injury. Therefore, based on calcium and ferric ions interference strategy, the cascade catalytic CaO/Tf/CUR offered synergistic combination of ferroptosis, Ca overload therapy and chemotherapy, which held a great promise in cancer treatment.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120937DOI Listing
July 2021

LC89 exerts antidiabetic effects through regulating hepatic glucagon response and gut microbiota in type 2 diabetic mice.

Food Funct 2021 Jul 26. Epub 2021 Jul 26.

Key Laboratory of Food Nutrition and Safety, Ministry of Education & Tianjin Key Laboratory of Food Nutrition and Safety, Food Biotechnology Engineering Research Center of Ministry of Education, Tianjin University of Science & Technology, Tianjin 300457, China. and Tianjin Agricultural University, Tianjin 300384, China.

Previous study suggests that Lactobacillus casei exhibits antihyperglycemic activity, however, the molecular mechanism of this has yet to be elucidated. Here, the anti-diabetic effects and underlying mechanisms of Lactobacillus casei LC89 are investigated in type 2 diabetes mellitus (T2DM) mice, which was induced by a high-fat diet (HFD) with streptozotocin (100 mg per kg BW). The results show that LC89 at a dose of 109 CFU day-1 decreases fasting blood glucose (FBG) and insulin levels by 35.12% and 28.37%, respectively, compared to the diabetes control (DC) group. Moreover, LC89 treatment improved the insulin resistance index (HOMA-IR), serum lipid profiles and inflammation cytokines. The real-time polymerase chain reaction indicated that LC89 markedly downregulates the mRNA expression of hepatic glucagon (GCG), glucagon receptor (GCGR), phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). Meanwhile, LC89 significantly decreases the abundance of Odoribacter, but increases the Alloprevotella, Bacteroides, Parabacteroides and Ruminococcus content. Therefore, LC89 plays a positive role in alleviating T2DM by regulating gut microbiota and glucagon signal pathway-related genes, and it may be a beneficial dietary supplement to regulate glucose metabolism in T2DM.
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http://dx.doi.org/10.1039/d1fo00882jDOI Listing
July 2021

The Antioxidant Resveratrol Protects against Chondrocyte Apoptosis by Regulating the COX-2/NF-B Pathway in Created Temporomandibular Osteoarthritis.

Biomed Res Int 2021 9;2021:9978651. Epub 2021 Jul 9.

Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou 310006, China.

Temporomandibular joint osteoarthritis (TMJOA) is characterized by chronic inflammatory degradation of mandibular condylar cartilage (MCC). Studies have found a positive correlation between inflammation and cyclooxygenase- (COX-) 2 in OA pathology. NF-B is a crucial transcription factor of inflammatory and immune responses in the cause of TMJOA pathology. Resveratrol (RES) plays a critical role in antioxidation and anti-inflammation. But, studies on the effects of RES on TMJOA are very limited. So, the purpose of this study is to investigate the antioxidant and protective effects of RES against MCC degradation through downregulating COX-2/NF-B expression. In vitro studies, the MCC cells were divided into three groups: the NC group, OA group, and RES group. The optimum dose of RES (10 M) was determined. The TMJOA model of mice was created by injection of collagenase. And mice were injected with RES (100 g/10 l) 3 times one week for 4 weeks in the RES group. The expressions of COX-2, P65, MMP1, MMP13, COL2, and ACAN were measured by RT-PCR. Morphological changes of MCC were studied with HE staining. The results showed that inflammation could induce MCC degradation in vitro and vivo, while RES could reverse the degradation. Meanwhile, RES could downregulate COX-2/NF-B/MMP expression and increase cartilage markers in vitro and vivo studies. The results indicated that RES treatment had antioxidant effects against chondrocyte apoptosis by downregulating the COX-2/NF-B pathway in created TMJOA.
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http://dx.doi.org/10.1155/2021/9978651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285176PMC
July 2021

Stability and Diffusion Properties of Insulin in Dissolvable Microneedles: A Multiscale Simulation Study.

Langmuir 2021 Jul 23. Epub 2021 Jul 23.

Beijing Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, P.R. China.

Microneedle (MN) technology has been proven to be promising to become an effective drug delivery route of insulin for diabetes treatment, with the advantages of high delivery efficiency, convenient management, and minimal risk of infection. However, efforts are still required to verify the insulin activity in MNs for further clinical application. Moreover, it is also essential to study the diffusion properties of insulin to understand the ability of various MN materials to control insulin release. Herein, we have combined all-atom molecular dynamics simulation and coarse-grained dissipative particle dynamics to systematically study insulin's structural stability and diffusion coefficient in polyvinyl alcohol and hyaluronic acid solutions. The all-atom simulation reveals the dissimilarities in the interaction mode between insulin and the two polymers. It also points out that the presence of the two polymers would not irreversibly impact the secondary structure of insulin, thereby ensuring regular insulin expression . Mesoscopic simulation results manifest that the diffusion coefficient of insulin in hyaluronic acid (HA) solution is greater than that of the polyvinyl alcohol (PVA) system. Meanwhile, through the study of insulin centroid trajectory, we have claimed two different diffusion mechanisms of insulin in polymer solution: The movement of insulin in the HA and water solution follows the Brownian motion rule. In comparison, the hopping effect of insulin has been observed in the PVA solution due to poor intermolecular affinity as well as lower polymer water solubility. By summarizing different diffusion mechanisms, this study can provide theoretical guidance for preparing insulin-loaded dissolvable MNs.
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http://dx.doi.org/10.1021/acs.langmuir.1c01434DOI Listing
July 2021

[Explore antioxidant quality markers of Hippophae tibetana based on "dry-method + wet-method" technology].

Zhongguo Zhong Yao Za Zhi 2021 Jun;46(11):2699-2709

School of Traditional Chinese Pharmacy,Beijing University of Chinese Medicine Beijing 102488,China.

The cross combination of dry-method(network pharmacology analysis) and wet-method(high-resolution mass spectro-metry with antioxidation experiment) was used to predict antioxidant quality markers(Q-markers) of Hippophae tibetana. Ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) was developed to rapidly separate and identify the chemical constituents in H. tibetana. Then in DPPH free radicals and superoxide anion scavenging experiment, the antioxidant activity of the four different polar parts with extracts of petroleumether, ethyl acetate, n-butanol and water was evaluated. Network pharmacology method was used for functional enrichment and pathway analysis to screen antioxidant-related components and preliminarily explain the mechanism of action. On this basis, multi-source information was integrated to predict the antioxidant Q-markers. The results showed that 51 components in H. tibetana were identified, including 18 flavonoids, 14 terpenoids, 6 alkaloids, 4 coumarins and phenylpropanoids, 3 volatile components and 2 polyphenols. The antioxidant capacity of different fractions: ethyl acetate > n-butanol > water > petroleum ether. The medicine mainly acted on PI3 K-Akt and FoxO signaling pathways to perform antioxidant effects through flavonoids such as quercetin, luteolin and kaempferol. According to the results of dry-method and wet-method, quercetin, luteolin and kaempferol, the representatives of poly-hydroxy flavone, may be the antioxidant Q-markers of H. tibetana. In this study, with the antioxidant Q-markers of H. tibetana as an example, an investigation model of predicting Q-marker was discussed based on the ternary system of composition, function and informatics, providing a scientific basis for the establishment of quality evaluation standards for H. tibetana.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20210122.301DOI Listing
June 2021

Genes Link Mitochondrial Dysfunction and Alpha-Synuclein Pathology in Sporadic Parkinson's Disease.

Front Cell Dev Biol 2021 6;9:612476. Epub 2021 Jul 6.

Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia.

Parkinson's disease (PD) is an age-related neurodegenerative disorder affecting millions of people worldwide. The disease is characterized by the progressive loss of dopaminergic neurons and spread of Lewy pathology (α-synuclein aggregates) in the brain but the pathogenesis remains elusive. PD presents substantial clinical and genetic variability. Although its complex etiology and pathogenesis has hampered the breakthrough in targeting disease modification, recent genetic tools advanced our approaches. As such, mitochondrial dysfunction has been identified as a major pathogenic hub for both familial and sporadic PD. In this review, we summarize the effect of mutations in 11 genes (, and ) on mitochondrial function as well as their relevance in the formation of Lewy pathology. Overall, these genes play key roles in mitochondrial homeostatic control (biogenesis and mitophagy) and functions (e.g., energy production and oxidative stress), which may crosstalk with the autophagy pathway, induce proinflammatory immune responses, and increase oxidative stress that facilitate the aggregation of α-synuclein. Thus, rectifying mitochondrial dysregulation represents a promising therapeutic approach for neuroprotection in PD.
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http://dx.doi.org/10.3389/fcell.2021.612476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291125PMC
July 2021

Comparative serum microRNA array analysis of the spleen-stomach dampness-heat syndrome in different diseases: Chronic hepatitis B and chronic gastritis.

Anat Rec (Hoboken) 2021 Jul 20. Epub 2021 Jul 20.

College of Basic Medical Sciences Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Spleen-stomach dampness-heat syndrome (SSDHS) is the common Traditional Chinese Medicine (TCM) syndrome observed in both chronic hepatitis B (CHB) and chronic gastritis (CG). The specialized TCM prescription for CHB and CG patients with SSDHS is same, but there is limited information about the biological characteristics of this TCM syndrome. This study aimed to identify the serum miRNAs profile for the SSDHS in two different diseases in order to evaluate the miRNA-mediated biological characteristics of this TCM syndrome. We performed comparative microarray analysis of serum miRNA expression profiles in 10 CHB patients with SSDHS (SSDHS-CHB), 10 CG patients with SSDHS (SSDHS-CG), and 10 healthy controls (HC). The selected miRNAs were further validated by qRT-PCR in 13 SSDHS-CHB patients, 13 SSDHS-CG patients, and 13 HC. Moreover, bioinformatics analysis (GO and KEGG pathway enrichment analyses) was applied to identify the involved target genes and pathways for these selected miRNAs. Nine significantly differentially expressed (SDE)-miRNAs in the SSDHS-CHB group and 24 SDE-miRNAs in the SSDHS-CG group were identified, compared with the HC group (fold change >2.0 and p < .05). Among these, upregulated hsa-miR-483-3p and downregulated hsa-miR-223-3p were identified as the common SDE-miRNAs for both SSDHS-CHB and SSDHS-CG groups. Bioinformatics analysis of the common SDE-miRNA's target genes showed their involvement in the regulation of inflammation, immune response, and tumorigenesis. SSDHS-specific hsa-miR-483-3p and hsa-miR-223-3p identified in this study indicated a relevance to the underlying biological basis of SSDHS, and may provide scientific basis for the application of same TCM prescription in CHB and CG.
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http://dx.doi.org/10.1002/ar.24690DOI Listing
July 2021

Precursor Supply Increases the Accumulation of 4-Hydroxy-6-(4-hydroxyphenyl)-α-pyrone after NRPS-PKS Gene Expression.

J Nat Prod 2021 Jul 21. Epub 2021 Jul 21.

Institut für Pharmazeutische Biologie und Biotechnologie, Fachbereich Pharmazie, Philipps-Universität Marburg, Robert-Koch Straße 4, 35037 Marburg, Germany.

Expression of a nonribosomal peptide synthetase-nonreducing polyketide synthase hybrid gene from PRB-2 in led to the accumulation of 4-hydroxy-6-(4-hydroxyphenyl)-α-pyrone (). Adding -hydroxybenzoic acid into the medium in which the overexpressing mutant is growing increased the product yield up to 5-fold. This strategy could be helpful for heterologous gene expression experiments requiring special substrates for product formation.
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http://dx.doi.org/10.1021/acs.jnatprod.1c00120DOI Listing
July 2021

Modifiable predictors of breastfeeding status and duration at 6 and 12 months postpartum.

Birth 2021 Jul 18. Epub 2021 Jul 18.

Health Promotion Unit, Population Health Research and Evaluation Hub, Sydney Local Health District, Camperdown, NSW, Australia.

Background: Breastfeeding practices are determined by complex multilevel factors. This study assessed pregnant women's knowledge of breastfeeding and intention to breastfeed and investigated modifiable predictors for breastfeeding status (exclusive or any breastfeeding) and duration at 6 and 12 months postpartum.

Materials And Methods: Longitudinal data were extracted from a trial in Sydney, Australia, 2017-19. Women (n = 1155) were recruited from antenatal clinics and followed up for telephone interviews at baseline (third trimester), then at 6 and 12 months postpartum. Data collected included mothers' demographics; knowledge of breastfeeding and intention to breastfeed; work status; support from caregivers; breastfeeding environment; breastfeeding status and duration. Multiple logistic and Cox regression models were built to identify predictors for breastfeeding.

Results: At baseline, most mothers knew the recommendation to exclusively breastfeed until 6 months (66%) and the benefits (65%). The modifiable predictors for breastfeeding duration at 12 months included the following: mothers' knowledge of the recommendation (adjusted hazard ratio (AHR) 0.73, 95% confidence interval (CI) 0.60-0.90) and the benefits of exclusive breastfeeding (AHR 0.68, 95% CI 0.55-0.82), intention to meet the recommendation (AHR 0.76, 95% CI 0.63-0.93), and intention to breastfeed for two years (AHR 0.38, 95% CI 0.27-0.52) measured at baseline; mothers not working or studying (AHR 0.70, 95% CI 0.55-0.89), having support from other caregivers (AHR 0.64, 95% CI 0.43-0.96), and having breastfeeding women around (AHR 0.80, 95% CI 0.65-0.98) measured at 6 months.

Conclusions: Support for women to meet the breastfeeding recommendations should commence during pregnancy and focus on breastfeeding education and enabling environments.
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http://dx.doi.org/10.1111/birt.12578DOI Listing
July 2021

Nomogram for Hepatic Venous Pressure Gradient in Cirrhotic Patients.

J Dig Dis 2021 Jul 17. Epub 2021 Jul 17.

Department of Gastroenterology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Aim: The hepatic venous pressure gradient (HVPG) plays an important role in the treatment and prognosis of patients with cirrhosis. The aim of our study is to develop and validate a nomogram for HVPG >12 mm Hg.

Methods: A retrospective study was performed to explore a nomogram for HVPG > 12 mm Hg in a training cohort and validated in another cohort. The discriminative ability and calibration of the nomogram were tested using the C-statistic, area under the curve (AUC) and calibration plots.

Results: The nomogram was based on portosystemic shunts identified on CT images, cirrhosis etiology and Child-Pugh grade. These parameters were significantly associated with HVPG >12 mm Hg (P<0.05 for both the training and validation cohorts). In the training cohort, the model showed good discrimination (C-statistic, AUC, and R of 0.71, 0.71 and 0.13, respectively) and good calibration. The total cutoff value was 112, and the sensitivity and specificity were 57.1% and 77.6%, respectively. Application of the nomogram in the validation cohort still yielded good discrimination (C-statistic, 0.75 [95% confidence interval (CI), 0.61-0.89],AUC, 0.75 and R ,0.16) and good calibration.

Conclusions: This nomogram is a convenient tool to predict HVPG >12 mm Hg in cirrhotic patients, and can help clinicians quickly identify decompensated cirrhotic patients. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/1751-2980.13033DOI Listing
July 2021

Clinical Analysis and Proteomic Screening Biomarkers for Graft-Versus-Host Disease After Liver Transplant.

Exp Clin Transplant 2021 Jul 16. Epub 2021 Jul 16.

From the Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University, Health Science Center, Xi'an, PR China.

Objectives: Graft-versus-host disease is a serious, fatal complication following liver transplantation. The diagnosis is challenging, owing to nonspecific clinical features and invasive procedures. High-throughput proteomics could provide an effective approach to identifying potential serum biomarkers for graft-versus-host disease.

Materials And Methods: We retrospectively analyzed the clinical information of 3 patients with graft-versus-host disease treated at our center from 2016 to 2018. We compared serum samples from the 3 patients with the disease, patients with excellent posttransplant outcomes, and healthy controls using mass spectrometry-based proteomics in discovery study. Probable peptides were further identified by a tandem mass spectrometry system and verified by enzyme-linked immunosorbent assay.

Results: Of 343 patients, 3 patients (0.875%) had graft-versus-host disease. Two of these patients died of sepsis and multiorgan failure despite intensive therapy. We observed no correlation between severity of clinical manifestation and prognosis; however, the patients with graft-versus-host disease had early onset and infection and showed worse outcome. Serum peptidome profiling showed 65 differentially expressed peaks among the 3 groups; the 2 peptides with the most significant changes (m/z values of 1950.29 and 2088.16) were further sequenced and identified as ATP citrate lyase and fibrinogen alpha chain. Western blot and enzyme-linked immunosorbent assay showed that both peptides gradually decreased among all groups.

Conclusions: Graft-versus-host disease is a complication of organ and tissue transplantation with a high mortality rate. Our identification of potential biomarkers for graft-versus-host disease associated with liver transplant may aid in diagnosis and help to reduce patient mortality in those cases.
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http://dx.doi.org/10.6002/ect.2021.0073DOI Listing
July 2021

miR-103-3p targets Ndel1 to regulate neural stem cell proliferation and differentiation.

Neural Regen Res 2022 Feb;17(2):401-408

Department of Human Anatomy, Institute of Neurobiology, Nantong University; Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China.

The regulation of adult neural stem cells (NSCs) is critical for lifelong neurogenesis. MicroRNAs (miRNAs) are a type of small, endogenous RNAs that regulate gene expression post-transcriptionally and influence signaling networks responsible for several cellular processes. In this study, miR-103-3p was transfected into neural stem cells derived from embryonic hippocampal neural stem cells. The results showed that miR-103-3p suppressed neural stem cell proliferation and differentiation, and promoted apoptosis. In addition, miR-103-3p negatively regulated NudE neurodevelopment protein 1-like 1 (Ndel1) expression by binding to the 3' untranslated region of Ndel1. Transduction of neural stem cells with a lentiviral vector overexpressing Ndel1 significantly increased cell proliferation and differentiation, decreased neural stem cell apoptosis, and decreased protein expression levels of Wnt3a, β-catenin, phosphor-GSK-3β, LEF1, c-myc, c-Jun, and cyclin D1, all members of the Wnt/β-catenin signaling pathway. These findings suggest that Ndel1 is a novel miR-103-3p target and that miR-103-3p acts by suppressing neural stem cell proliferation and promoting apoptosis and differentiation. This study was approved by the Animal Ethics Committee of Nantong University, China (approval No. 20200826-003) on August 26, 2020.
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http://dx.doi.org/10.4103/1673-5374.317987DOI Listing
February 2022

A Novel Surgical Approach for Rhinophyma: Experience From a Cohort of Thirty Patients.

J Craniofac Surg 2021 Jul 15. Epub 2021 Jul 15.

Department of Dermatology, Shuguang Hospital Affiliated to Shanghai University of TCM, Shanghai, China.

Background: Rhinophyma is the severe rosacea whit hypertrophy of sebaceous glands in nasal tissue, which severely influences the patient's appearance. Surgical therapy is the best method for treating moderate-to-severe rhinophyma. In this study, we used a new ameliorated scarification for 30 patients with moderate-to-severe rhinophyma.

Objective: To observe the effect of five-blades scratcher surgery on moderate-to severe rhinophyma between 2016 and 2019 in our center.

Materials And Methods: A total of 30 patients were treated with five-blades scratcher under tumescent anesthesia. Outcomes were determined by a patient questionnaire.

Results: Of 30 patients, all of them answered the questionnaire and were included in this study with a follow-up time of 12 months. Cosmetic results were evaluated as very good or good in 90% of patients. The majority of patients (87%) were very satisfied or satisfied with the postoperative result. Surgical treatment of rhinophyma improved patients' quality of life in 67% of patients. Recurrence of rhinophyma was detected in 7% of patients. In all, 100% of the patients stated that they would recommend this treatment to others.

Conclusions: Five-blades scratcher is an effective therapy for rhinophyma with excellent outcome.
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http://dx.doi.org/10.1097/SCS.0000000000007963DOI Listing
July 2021

Two unusual cases of autologous HSCT related TMA with kidney injury.

Ann Palliat Med 2021 Jul 8. Epub 2021 Jul 8.

Department of Nephrology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Kidney injury caused by transplant-associated thrombotic microangiopathy (TA-TMA) in patients who underwent allogeneic hematopoietic stem cell transplantation (allo HSCT) is relatively frequent. However, it is rarely reported in patients undergoing autologous HSCT (aHSCT). There are a few studies reported that TA-TMA could occur in pediatric patients undergoing aHSCT, but the condition in adult patients is rarely described. Furthermore, almost all the patients who suffered from TA-TMA developed typical and severe manifestations which should be treated with aggressive target therapy. Nevertheless, we presented two cases of kidney injury caused by TA-TMA after aHSCT with specific clinical features. Case 1, a 33-year-old Chinese male diagnosed with Hodgkin's lymphoma developed TA-TMA -associated kidney injury 4 months after transplantation. Case 2, a 49-year-old Chinese female with central nervous lymphoma developed TA-TMA-related kidney injury 3 months after transplantation. Both patients presented "mild" and atypical features of TA-TMA and their kidney function was managed effectively with low-dose prednisone therapy. TA-TMA related kidney injury can occur in patients who underwent aHSCT. Patients with TA-TMA could develop atypically "mild" features. Low-dose prednisone may be effective in place of routine eculizumab treatment regimen. We recommend that clinicians prompt an investigation for TA-TMA in patients presenting kidney injury in the background of aHSCT to facilitate early diagnosis.
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http://dx.doi.org/10.21037/apm-21-226DOI Listing
July 2021

FRET-Based Screening Identifies p38 MAPK and PKC Inhibition as Targets for Prevention of Seeded α-Synuclein Aggregation.

Neurotherapeutics 2021 Jul 13. Epub 2021 Jul 13.

Department of Experimental Medicine, Neural Plasticity and Repair, Lund University, Lund, Sweden.

Aggregation of α-synuclein is associated with neurodegeneration and a hallmark pathology in synucleinopathies. These aggregates are thought to function as prion-like particles where the conformation of misfolded α-synuclein determines the traits of the induced pathology, similar to prion diseases. Still, little is known about the molecular targets facilitating the conformation-specific biological effects, but their identification could form the basis for new therapeutic interventions. High-throughput screening of annotated compound libraries could facilitate mechanistic investigation by identifying targets with impact on α-synuclein aggregation. To this end, we developed a FRET-based cellular reporter in HEK293T cells, with sensitivity down to 6.5 nM α-synuclein seeds. Using this model system, we identified GF109203X, SB202190, and SB203580 as inhibitors capable of preventing induction of α-synuclein aggregation via inhibition of p38 MAPK and PKC, respectively. We further investigated the mechanisms underlying the protective effects and found alterations in the endo-lysosomal system to be likely candidates of the protection. We found the changes did not stem from a reduction in uptake but rather alteration of lysosomal abundance and degradative capacity. Our findings highlight the value high-throughput screening brings to the mechanistic investigation of α-synuclein aggregation while simultaneously identifying novel therapeutic compounds.
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http://dx.doi.org/10.1007/s13311-021-01070-1DOI Listing
July 2021

Cross-Dataset Point Cloud Recognition Using Deep-Shallow Domain Adaptation Network.

IEEE Trans Image Process 2021 Jul 13;PP. Epub 2021 Jul 13.

In this work, we propose a novel two-view domain adaptation network named Deep-Shallow Domain Adaptation Network (DSDAN) for 3D point cloud recognition. Different from the traditional 2D image recognition task, the valuable texture information is often absent in point cloud data, making point cloud recognition a challenging task, especially in the cross-dataset scenario where the training and test data exhibit a considerable distribution mismatch. In our DSDAN method, we tackle the challenging cross-dataset 3D point cloud recognition task from two aspects. On one hand, we propose a two-view learning framework, such that we can effectively leverage multiple feature representations to improve the recognition performance. To this end, we propose a simple and efficient Bag-of-Points feature method, as a complementary view to the deep representation. Moreover, we also propose a cross view consistency loss to boost the two-view learning framework. On the other hand, we further propose a two-level adaptation strategy to effectively address the domain distribution mismatch issue. Specifically, we apply a feature-level distribution alignment module for each view, and also propose an instance-level adaptation approach to select highly confident pseudo-labeled target samples for adapting the model to the target domain, based on which a co-training scheme is used to integrate the learning and adaptation process on the two views. Extensive experiments on the benchmark dataset show that our newly proposed DSDAN method outperforms the existing state-of-the-art methods for the cross-dataset point cloud recognition task.
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http://dx.doi.org/10.1109/TIP.2021.3092818DOI Listing
July 2021

Basic approaches, challenges and opportunities for the discovery of small molecule anti-tumor drugs.

Am J Cancer Res 2021 15;11(6):2386-2400. Epub 2021 Jun 15.

National Engineering Laboratory for Deep Process of Rice and Byproducts, College of Food Science and Engineering, Central South University of Forestry and Technology Changsha 410004, Hunan, China.

Chemotherapy is one of the main treatments for cancer, especially for advanced cancer patients. In the past decade, significant progress has been made with the research into the molecular mechanisms of cancer cells and the precision medicine. The treatment on cancer patients has gradually changed from cytotoxic chemotherapy to precise treatment strategy. Research into anticancer drugs has also changed from killing effects on all cells to targeting drugs for target genes. Besides, researchers have developed the understanding of the abnormal physiological function, related genomics, epigenetics, and proteomics of cancer cells with cancer genome sequencing, epigenetic research, and proteomic research. These technologies and related research have accelerated the development of related cancer drugs. In this review, we summarize the research progress of anticancer drugs, the current challenges, and future opportunities.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263657PMC
June 2021

Three new polyketides from vasR2 gene over-expressed mutant strain of Verrucosispora sp. NS0172.

Chin J Nat Med 2021 Jul;19(7):536-539

Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China. Electronic address:

Over-expression of the pathway specific positive regulator gene is an effective way to activate silent gene cluster. In the curret study, the SARP family regulatory gene, vasR2, was over-expressed in strain Verrucosispora sp. NS0172 and the cryptic gene cluster responsible for the biosynthesis of pentaketide ansamycin was partially activated. Two tetraketides (1 and 2) and a triketide (3) ansamycins, together with five known compounds (4-8), were isolated and elucidated from strain NS0172OEvasR2. Their NMR data were completely assigned by analysis of their HR-ESI-MS and H, C NMR, HMQC, HMBC and H-H COSY spectra.
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http://dx.doi.org/10.1016/S1875-5364(21)60053-5DOI Listing
July 2021

Engagement, satisfaction, retention and behavioural outcomes of linguistically diverse mothers and infants participating in an Australian early obesity prevention trial.

Health Promot J Austr 2021 Jul 10. Epub 2021 Jul 10.

Sydney School of Public Health, The University of Sydney, Sydney, NSW, Australia.

Background: Early obesity prevention research interventions in Australia generally expect participants to be able to communicate in English, but do not account for other languages. This study aimed to investigate engagement, satisfaction, retention and behavioural outcomes of linguistically diverse participants from a mainstream early childhood obesity prevention trial.

Methods: Healthy Beginnings is a nurse-led intervention based in Sydney, supporting families with optimal infant feeding and active play via telephone. This secondary analysis assessed participant engagement in the nurse telephone calls (call completions), satisfaction and behavioural outcomes (6- and 12-month survey data) and retention (survey completions), in the first year of life according to participants' language spoken at home (English or other language).

Results: Of 1155 mothers, 533 (46%) spoke a language other than English at home. Significantly fewer mothers speaking a language other than English completed the 6-month survey (79%) compared to those speaking English (84%), yet mothers speaking a language other than English who completed the program were more satisfied with the program overall. Significantly fewer mothers speaking a language other than English completed the final four nurse calls (of six) (56%-65%) compared to those speaking English (70%-80%). Adjusted odds ratios showed selected behavioural outcomes were significantly more positive for participants speaking English at home.

Conclusions: Healthy Beginnings trial participants who spoke a language other than English at home had less favourable engagement, retention and behavioural outcomes compared to those who spoke English. So what? Early obesity prevention interventions should consider cultural adaptations to improve engagement and effectiveness among culturally and linguistically diverse families.
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http://dx.doi.org/10.1002/hpja.521DOI Listing
July 2021

Augmenter of liver regeneration-mediated mitophagy protects against hepatic ischemia/reperfusion injury.

Am J Transplant 2021 Jul 9. Epub 2021 Jul 9.

Department of Cell Biology and Municipal, Laboratory of Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing, China.

Augmenter of liver regeneration (ALR) is an anti-apoptotic protein found mainly in mitochondria. It protects hepatocytes from ischemia-reperfusion (I/R) injury, but the underlying mechanism is not clear. We found that in rats, delivery of the ALR gene alleviated hepatic I/R injury during orthotopic liver transplantation as evidenced by reduced serum aminotransferase, oxidative stress and apoptosis, and increased expression of autophagy markers. In an in-vitro hypoxia/reoxygenation (H/R) model, overexpression of the ALR gene activated autophagy and relieved defective mitophagy via the PINK1/Parkin pathway. Mechanistically, ALR transfection induced the expression of mitofusin 2 (Mfn2) in the H/R model, which led to PINK1 accumulation and mitochondrial translocation of Parkin. Deletion of Mfn2 abolished mitophagy activation induced by ALR transfection, promoted mitochondrial dysfunction, and eventually inhibited cell apoptosis. Mfn2 administration prevented the inhibition of mitophagy in ALR-knockout (KO) cells, thus attenuated mitochondrial dysfunction and cell apoptosis. In heterozygous ALR-knockout mice treated with a warm I/R injury, marked aggravation of liver injury was associated with mitophagy inhibition and reduction in Mfn2 expression. Taken together, our results confirm that ALR accelerated Parkin translocation and mitophagy via Mfn2, and protected hepatocytes from I/R-induced injury. Our findings provide a novel rationale for the treatment of hepatic I/R injury.
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http://dx.doi.org/10.1111/ajt.16757DOI Listing
July 2021

Fatigue and Its Association With Quality of Life Among Carers of Patients Attending Psychiatric Emergency Services During the COVID-19 Pandemic.

Front Psychiatry 2021 22;12:681318. Epub 2021 Jun 22.

Unit of Psychiatry, Department of Public Health and Medicinal Administration, Faculty of Health Sciences, Centre for Cognitive and Brain Sciences, University of Macau, Macao, China.

Carers of psychiatric patients often suffered from mental and physical burden during the coronavirus disease 2019 (COVID-19) pandemic due to the lack of mental health services. This study investigated the pattern of fatigue and its association with quality of life (QOL) among the carers of patients attending psychiatric emergency services during the COVID-19 pandemic. In this cross-sectional study, carers of patients attending psychiatric emergency services during the COVID-19 pandemic were consecutively included. Fatigue, insomnia symptoms, depressive symptoms, and QOL were assessed with standardized instruments. A total of 496 participants were included. The prevalence of fatigue was 44.0% (95% CI = 39.6-48.4%). Multivariate logistic regression analysis revealed that fatigue was positively associated with higher education level (OR = 1.92, < 0.01) and more severe depressive (OR = 1.18, < 0.01) and insomnia symptoms (OR = 1.11, < 0.01). ANCOVA analysis revealed that the QOL was significantly lower in carers with fatigue compared with those without (P = 0.03). Fatigue was common among carers of patients attending psychiatric emergency services during the COVID-19 pandemic. Considering the adverse impact of fatigue on QOL and other health outcomes, routine screening and appropriate intervention for fatigue are warranted for this subpopulation.
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http://dx.doi.org/10.3389/fpsyt.2021.681318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257938PMC
June 2021

[Correlation between Contrast-enhanced Ultrasound and Risk of Tumor Recurrence in Papillary Thyroid Carcinoma].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2021 Jun;43(3):343-349

Department of Ultrasound,Medical School of Chinese PLA,Beijing 100853,China.

Objective To explore the association between contrast-enhanced ultrasound and risk of tumor recurrence in papillary thyroid carcinoma(PTC). Methods A total of 287 PTCs in 287 patients who underwent surgery,conventional ultrasound,and contrast-enhanced ultrasound(CEUS)were enrolled in this study.According to 2015 American Thyroid Association(ATA)Modified Initial Risk Stratification System,the patients were categorized into three groups:low risk,intermediate risk,and high risk.The CEUS patterns of PTCs were compared between different risk stratifications. Results Hypo-enhancement was presented in 57.6% of ATA low-risk PTCs,iso-enhancement in 62.3% of ATA intermediate-risk PTCs,and hyper-enhancement in 48.2% of ATA high-risk PTCs(<0.0001).The risk stratifications and enhanced intensity in PTC showcased a positive correlation(Spearman's rho of 0.442,<0.0001)and a linear trend( value of 55.921,<0.0001).Higher enhancement intensity corresponded to higher risk stratification.Ordinal logistic regression analysis indicated that PTCs with hyper-enhancement and iso-enhancement presented higher risks than those with hypo-enhancement after age and gender were adjusted,and the values were 17.5(8.4-36.2)and 3.4(2.0-5.8),respectively. Conclusions CEUS patterns correlate intimately with the recurrence risk in PTC.Hyper-enhancement PTCs tend to present high risks,while hypo-enhancement PTCs tend to present low risks of recurrence.
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http://dx.doi.org/10.3881/j.issn.1000-503X.13828DOI Listing
June 2021

[Validated Nomogram Predicting Clinical Outcome after Radiofrequency Ablation in the Treatment of Papillary Thyroid Microcarcinoma].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2021 Jun;43(3):322-327

Department of Ultrasound,the First Medical Center of Chinese PLA General Hospital,Beijing 100853,China.

Objective To establish a prediction model for the short-term efficacy of percutaneous ultrasound-guided radiofrequency ablation(RFA)in the treatment of papillary thyroid microcarcinoma(PTMC). Methods We retrospectively analyzed the preoperative and follow-up data of 159 patients with PTMC who underwent percutaneous ultrasound-guided RFA treatment in the Department of Ultrasound,the First Medical Center of Chinese PLA General Hospital from January to December in 2018.The association with 12-month tumor status(end event)was evaluated by multivariate logistic regression model.A nomogram was built to predict the risk of tumors which did not disappear completely within 12 months after RFA. Results We found that gender(=0.017),age(=0.047),and calcification(=0.049)were the strongest predictors for establishing the model.The tumor maximum diameter and RFA energy were the secondary relevant factors for establishing the model.The constructed model showed good performance in both training cohort(AUC=0.762)and validation cohort(AUC=0.740). Conclusion A quantitative model was established for predicting the tumor status within one year after treatment of PTMC by RFA,which can accurately predict the short-term efficacy of RFA and provide a clinical basis for explaining the recovery results of patients.
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http://dx.doi.org/10.3881/j.issn.1000-503X.13813DOI Listing
June 2021

Effect of Sodium Salicylate on Calcium Currents and Exocytosis in Cochlear Inner Hair Cells: Implications for Tinnitus Generation.

Neurosci Bull 2021 Jul 7. Epub 2021 Jul 7.

Clinical Laboratory Center, Children's Hospital of Fudan University, Shanghai, 201102, China.

Sodium salicylate is an anti-inflammatory medication with a side-effect of tinnitus. Here, we used mouse cochlear cultures to explore the effects of salicylate treatment on cochlear inner hair cells (IHCs). We found that IHCs showed significant damage after exposure to a high concentration of salicylate. Whole-cell patch clamp recordings showed that 1-5 mmol/L salicylate did not affect the exocytosis of IHCs, indicating that IHCs are not involved in tinnitus generation by enhancing their neuronal input. Instead, salicylate induced a larger peak amplitude, a more negative half-activation voltage, and a steeper slope factor of Ca current. Using noise analysis of Ca tail currents and qRT-PCR, we further found that salicylate increased the number of Ca channels along with Ca1.3 expression. All these changes could act synergistically to enhance the Ca influx into IHCs. Inhibition of intracellular Ca overload significantly attenuated IHC death after 10 mmol/L salicylate treatment. These results implicate a cellular mechanism for tinnitus generation in the peripheral auditory system.
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http://dx.doi.org/10.1007/s12264-021-00747-zDOI Listing
July 2021

Infant feeding and growth trajectories in early childhood: the application and comparison of two longitudinal modelling approaches.

Int J Obes (Lond) 2021 Jul 6. Epub 2021 Jul 6.

School of Public Health and Sydney Medical School, The University of Sydney, Sydney, Australia.

Background/objectives: The role of infant feeding practices in longitudinal growth trajectories in children remains equivocal. This study utilised two longitudinal approaches to examine the associations of infant feeding mode (breastfeeding, mixed feeding, formula feeding), breastfeeding duration, and the timing of solid foods introduction with body mass index (BMI) z-score in early childhood.

Subjects/methods: Secondary analyses of data from the Healthy Beginnings Trial were conducted. Infant feeding practices were reported by mothers at 6, 12, and 24 months of child age. Child weight and length were measured at birth, 12, 24, 42, and 60 months. Two longitudinal approaches: linear spline multilevel model (LSMM) and group-based trajectory modelling (GBTM) were used to describe BMI z-score trajectories and assess its associations with infant feeding practices.

Results: The LSMM approach demonstrated that the breastfeeding group showed lower BMI z-scores from ages 12 to 60 months than the mixed feeding and formula feeding groups. Children who were breastfed for ≥ 6 versus < 6 months exhibited a lower BMI z-score trajectory from ages 12 to 60 months. Results from the GBTM approach revealed that the mixed feeding (OR: 1.83, 95%CI 1.04, 3.21) and the formula feeding group (OR: 2.00, 95%CI 0.67, 5.92) showed a tendency for higher odds of following the "High BMIz" trajectory than the breastfeeding group. Breastfeeding duration ≥6 versus < 6 months was linked with lower odds of following the "High BMIz" trajectory (OR 0.65, 95%CI 0.43, 0.98). Both approaches revealed no evidence of an association between the timing of solid foods introduction and BMI z-score trajectory.

Conclusions: The two longitudinal approaches revealed similar findings that infant feeding mode and breastfeeding duration, but not the timing of solid foods introduction, were associated with BMI z-score trajectory in early childhood. The findings provide robust longitudinal evidence to encourage and support extended breastfeeding for childhood obesity prevention.
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http://dx.doi.org/10.1038/s41366-021-00892-5DOI Listing
July 2021

Association of fluid balance trajectories with clinical outcomes in patients with septic shock: a prospective multicenter cohort study.

Mil Med Res 2021 07 6;8(1):40. Epub 2021 Jul 6.

Department of Critical Care Medicine, Fuxing Hospital, Capital Medical University, No. 20, Street Fuxingmenwai, Beijing, Xicheng District, China.

Background: Septic shock has a high incidence and mortality rate in Intensive Care Units (ICUs). Earlier intravenous fluid resuscitation can significantly improve outcomes in septic patients but easily leads to fluid overload (FO), which is associated with poor clinical outcomes. A single point value of fluid cannot provide enough fluid information. The aim of this study was to investigate the impact of fluid balance (FB) latent trajectories on clinical outcomes in septic patients.

Methods: Patients were diagnosed with septic shock during the first 48 h, and sequential fluid data for the first 3 days of ICU admission were included. A group-based trajectory model (GBTM) which is designed to identify groups of individuals following similar developmental trajectories was used to identify latent subgroups of individuals following a similar progression of FB. The primary outcomes were hospital mortality, organ dysfunction, major adverse kidney events (MAKE) and severe respiratory adverse events (SRAE). We used multivariable Cox or logistic regression analysis to assess the association between FB trajectories and clinical outcomes.

Results: Nine hundred eighty-six patients met the inclusion criteria and were assigned to GBTM analysis, and three latent FB trajectories were detected. 64 (6.5%), 841 (85.3%), and 81 (8.2%) patients were identified to have decreased, low, and high FB, respectively. Compared with low FB, high FB was associated with increased hospital mortality [hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.22-2.17], organ dysfunction [odds ratio (OR) 2.18, 95% CI 1.22-3.42], MAKE (OR 1.80, 95% CI 1.04-2.63) and SRAE (OR 2.33, 95% CI 1.46-3.71), and decreasing FB was significantly associated with decreased MAKE (OR 0.46, 95% CI 0.29-0.79) after adjustment for potential covariates.

Conclusion: Latent subgroups of septic patients followed a similar FB progression. These latent fluid trajectories were associated with clinical outcomes. The decreasing FB trajectory was associated with a decreased risk of hospital mortality and MAKE.
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http://dx.doi.org/10.1186/s40779-021-00328-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258941PMC
July 2021

The crosstalk between the Notch, Wnt, and SHH signaling pathways in regulating the proliferation and regeneration of sensory progenitor cells in the mouse cochlea.

Cell Tissue Res 2021 Jul 5. Epub 2021 Jul 5.

NHC Key Laboratory of Hearing Medicine, ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China.

Sensory hair cells (HCs) are highly susceptible to damage by noise, ototoxic drugs, and aging. Although HCs cannot be spontaneously regenerated in adult mammals, previous studies have shown that signaling pathways are involved in HC regeneration in the damaged mouse cochlea. Here, we used a Notch antagonist (DAPT), a Wnt agonist (QS11), and recombinant Sonic hedgehog (SHH) protein to investigate their concerted actions underlying HC regeneration in the mouse cochlea after neomycin-induced damage both in vivo and in vitro. With DAPT, the numbers of HCs increased, and supporting cell (SC) proliferation was seen in both the intact and damaged cochlear sensory epithelia, while these numbers were unchanged in the presence of QS11. When simultaneously treated with DAPT and QS11, the number of HCs increased dramatically, and much greater SC proliferation was seen in the cochlear epithelium. In transgenic mice with both Notch1 conditional knockout and β-catenin over-expression, cochlear SC proliferation and HC regeneration were more obvious than in either Notch1 knockout or β-catenin over-expressing mice separately. When cochleae were treated with DAPT, QS11, and SHH together, SC proliferation was even greater, and this proliferation was seen in both the HC region and the greater epithelial ridge. High-throughput RNA sequencing was used to identify the differentially expressed genes between all groups, and the results showed that the SHH and Wnt signaling pathways are involved in SC proliferation. Our study suggests that co-regulation of the Notch, Wnt, and SHH signaling pathways promotes extensive cell proliferation and regeneration in the mouse cochlea.
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http://dx.doi.org/10.1007/s00441-021-03493-wDOI Listing
July 2021
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