Publications by authors named "Tingting Yang"

337 Publications

Bimetallic Metal-Organic Frameworks: Enhanced Peroxidase-like Activities for the Self-Activated Cascade Reaction.

ACS Appl Mater Interfaces 2021 Jul 27. Epub 2021 Jul 27.

School of Chemistry, Xi'an Key Laboratory of Sustainable Energy Material Chemistry, Xi'an Jiaotong University, Xi'an 710049, P. R. China.

Metal-organic frameworks (MOFs) are significant useful molecular materials as a result of their high surface area and flexible catalytic activities by tuning the metal centers and ligands. MOFs have attracted great attention as efficient nanozymes recently; however, it is still difficult to understand polymetallic MOFs for enzymatic catalysis because of their complicated structure and interactions. Herein, bimetallic NiFe MOF octahedra were well prepared and exhibited enhanced peroxidase-like activities. The synergistic effect of Fe and Ni atoms was systematically investigated by electrochemistry, X-ray photoelectron spectrometry, (XPS) and Raman techniques. The electrons tend to transfer from Ni to Fe in NiFe MOFs, and the resulting Fe is ready to decompose HO and generate OH by a Fenton-like reaction. After integration with glucose oxidase (GOx), which can downgrade the pH value and generate HO by oxidation of glucose, a self-activated cascade reagent is therefore established for efficiently inducing cell death. The changes of cell morphology, DNA, and protein are also successfully recorded during the cell death process by Raman spectroscopy and fluorescence imaging.
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http://dx.doi.org/10.1021/acsami.1c05615DOI Listing
July 2021

5-HT recruits distinct neurocircuits to inhibit hunger-driven and non-hunger-driven feeding.

Mol Psychiatry 2021 Jul 21. Epub 2021 Jul 21.

Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.

Obesity is primarily a consequence of consuming calories beyond energetic requirements, but underpinning drivers have not been fully defined. 5-Hydroxytryptamine (5-HT) neurons in the dorsal Raphe nucleus (5-HT) regulate different types of feeding behavior, such as eating to cope with hunger or for pleasure. Here, we observed that activation of 5-HT to hypothalamic arcuate nucleus (5-HT → ARH) projections inhibits food intake driven by hunger via actions at ARH 5-HT and 5-HT receptors, whereas activation of 5-HT to ventral tegmental area (5-HT → VTA) projections inhibits non-hunger-driven feeding via actions at 5-HT receptors. Further, hunger-driven feeding gradually activates ARH-projecting 5-HT neurons via inhibiting their responsiveness to inhibitory GABAergic inputs; non-hunger-driven feeding activates VTA-projecting 5-HT neurons through reducing a potassium outward current. Thus, our results support a model whereby parallel circuits modulate feeding behavior either in response to hunger or to hunger-independent cues.
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http://dx.doi.org/10.1038/s41380-021-01220-zDOI Listing
July 2021

Increased serum interleukin-34 levels as a novel diagnostic and prognostic biomarker in patients with acute ischemic stroke.

J Neuroimmunol 2021 Jun 30;358:577652. Epub 2021 Jun 30.

Department of Neurology, Affiliated Hospital of Xuzhou Medical University, No. 99 Huaihai West Road, Quanshan Distric, Xuzhou, Jiangsu, China. Electronic address:

Background: Recent data reveal that interleukin-34 (IL-34) can drive inflammatory response, thereby participating in the pathogenesis of inflammatory diseases. However, the potential effect of IL-34 in acute ischemic stroke (AIS) remains unknown. The purpose of this study was to explore whether the levels of serum IL-34 were correlated with clinical severity or prognosis in AIS patients.

Methods: In this prospective cohort study, serum IL-34 levels were detected in 150 healthy controls and 155 AIS patients. Univariate and multivariate logistic regression analysis were conducted to investigate the effect of IL-34 on the diagnosis and prognosis of AIS. ROC curve was utilized to evaluate predictive values for IL-34.

Results: Serum IL-34 levels at admission were significantly higher in AIS patients than those in the healthy controls. Univariate and multivariate logistics regression analysis showed that IL-34 was an independent predictor of occurrence and functional outcome of AIS. The ROC curve demonstrated that IL-34 had a good predictive effect on the diagnosis and prognosis of AIS.

Conclusions: IL-34 can be used as a novel and independent diagnostic and predicting prognostic biomarker in AIS.
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http://dx.doi.org/10.1016/j.jneuroim.2021.577652DOI Listing
June 2021

SS18 regulates pluripotent-somatic transition through phase separation.

Nat Commun 2021 07 2;12(1):4090. Epub 2021 Jul 2.

Laboratory of Cell Fate Control, School of Life Sciences, Westlake University, Hangzhou, China.

The transition from pluripotent to somatic states marks a critical event in mammalian development, but remains largely unresolved. Here we report the identification of SS18 as a regulator for pluripotent to somatic transition or PST by CRISPR-based whole genome screens. Mechanistically, SS18 forms microscopic condensates in nuclei through a C-terminal intrinsically disordered region (IDR) rich in tyrosine, which, once mutated, no longer form condensates nor rescue SS18 defect in PST. Yet, the IDR alone is not sufficient to rescue the defect even though it can form condensates indistinguishable from the wild type protein. We further show that its N-terminal 70aa is required for PST by interacting with the Brg/Brahma-associated factor (BAF) complex, and remains functional even swapped onto unrelated IDRs or even an artificial 24 tyrosine polypeptide. Finally, we show that SS18 mediates BAF assembly through phase separation to regulate PST. These studies suggest that SS18 plays a role in the pluripotent to somatic interface and undergoes liquid-liquid phase separation through a unique tyrosine-based mechanism.
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http://dx.doi.org/10.1038/s41467-021-24373-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253816PMC
July 2021

Comparison of microstructural imaging of the root canal isthmus using propagation-based X-ray phase-contrast and absorption micro-computed tomography.

J Microsc 2021 Jun 18. Epub 2021 Jun 18.

School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin, People's Republic of China.

Clear and complete microstructural imaging of the root canal isthmus is an important part of pathological investigations in research and clinical practice. X-ray micro-computed tomography (μCT) is a widely used non-destructive imaging technique, which allows for distortion-free three-dimensional (3D) visualisation. While absorption μCT typically has poor contrast resolution for observing the root canal isthmus, especially for weak-absorbing tissues, propagation-based X-ray phase-contrast imaging (PBI) is a powerful imaging method, which in its combination with μCT (PB-PCμCT) enables high-resolution and high-contrast microstructural imaging of the weak-absorbing tissues in samples. To investigate the feasibility and ability of PB-PCμCT in microstructural imaging of the root canal isthmus, conventional absorption μCT and PB-PCμCT experiments were performed. The two-dimensional (2D) and 3D comparison results demonstrated that, compared to absorption μCT, PB-PCμCT has the ability to image the root canal isthmus more clearly and completely, and thus, it has great potential to serve as a valuable tool for biomedical and preclinical studies on the root canal isthmus.
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http://dx.doi.org/10.1111/jmi.13042DOI Listing
June 2021

Eye Avoidance of Threatening Facial Expressions in Parents of Children with ASD.

Neuropsychiatr Dis Treat 2021 9;17:1869-1879. Epub 2021 Jun 9.

School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, 230022, People's Republic of China.

Objective: Previous research found that autism spectrum disorder (ASD) was characterized by eye avoidance of threatening facial expressions. However, it still remains unclear as to whether these abnormalities are present in parents of children with ASD. Our study aimed to investigate the gaze patterns of parents of children with ASD in the threatening facial expressions.

Methods: Thirty-four parents of children with ASD and 35 parents of typically developing (TD) children participated in our study. We investigated the total fixation time of participants when they viewed different facial expression (eg, happy, fearful, angry, sad) videos and examined changes in the fixation duration over time.

Results: We observed the following: a) the total fixation time of the parents of children with ASD on the eyes of fearful faces was significantly shorter than that of the normal group, and the difference lasted for five seconds (four to six seconds, eight to nine seconds) throughout the process; and b) The parents of children with ASD avoided the eyes of angry expression faces at around five seconds after the stimulus onset.

Conclusion: We concluded that parents of children with ASD tended to avoid the eyes of threatening expression faces while viewing the dynamic emotions video.
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http://dx.doi.org/10.2147/NDT.S300491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203098PMC
June 2021

Iron Overload-Induced Ferroptosis Impairs Porcine Oocyte Maturation and Subsequent Embryonic Developmental Competence .

Front Cell Dev Biol 2021 28;9:673291. Epub 2021 May 28.

Department of Animals Sciences, College of Animal Sciences, Jilin University, Changchun, China.

Accumulating evidence indicates that ferroptosis is an iron-dependent form of regulated cell death. This type of iron-dependent programmed cell death is different from traditional forms of regulated cell death, such as apoptosis and autophagy. However, the role of ferroptosis in porcine oocyte maturation and the associated mechanism remain unclear. In the present research, we investigated the effects of ferric ammonium citrate (FAC), a specific ferroptosis inducer, on porcine oocyte meiotic maturation and quality and subsequent embryonic developmental competence. FAC treatment caused obvious accumulation of intracellular ferrous ions in porcine oocytes. At the end of the maturation (IVM) period, there was a significant decrease in the polar body (PB) extrusion rate and an increase in the percentage of abnormal oocytes in the FAC treatment groups, indicating that iron overload-induced ferroptosis may suppress the meiotic process during porcine oocyte maturation. We also found that after FAC treatment, the subsequent two-cell rate, four-cell rate and blastocyst formation rate were significantly decreased in porcine parthenogenetic activation (PA) embryos, indicating that iron overload-induced ferroptosis decreased porcine oocyte quality. Further analysis revealed that FAC treatment not only enhanced intracellular reactive oxygen species (ROS) generation, decreased intracellular free thiol levels and induced mitochondrial dysfunction but also triggered autophagy in porcine oocytes. Taken together, these findings suggest that iron overload-induced ferroptosis impairs porcine oocyte meiosis and decreases porcine oocyte quality, possibly by increasing oxidative stress, inducing mitochondrial dysfunction and triggering autophagy.
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http://dx.doi.org/10.3389/fcell.2021.673291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194094PMC
May 2021

Evaluating BEST1 mutations in pluripotent stem cell-derived retinal pigment epithelial cells.

Methods Enzymol 2021 27;654:365-382. Epub 2021 Feb 27.

Department of Ophthalmology, Columbia University, New York, NY, United States. Electronic address:

Bestrophin-1 (BEST1) is a calcium-activated chloride channel (CaCC) predominantly expressed at the basolateral membrane of the retinal pigment epithelium (RPE). Over 250 mutations in the BEST1 gene have been documented to cause at least five retinal degenerative disorders, commonly termed bestrophinopathies, to which no treatment is currently available. Therefore, understanding the influences of BEST1 disease-causing mutations on the physiological function of BEST1 in RPE is critical for deciphering the pathology of bestrophinopathies and developing therapeutic strategies for patients. However, this task has been impeded by the rarity of BEST1 mutations and limited accessibility to native human RPE cells. Here, we describe a pluripotent stem cell (PSC)-based pipeline for reproducibly generating RPE cells expressing endogenous or exogenous mutant BEST1, which provides us with a powerful "disease-in-a-dish" approach for studying BEST1 mutations in physiological environments.
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http://dx.doi.org/10.1016/bs.mie.2021.01.004DOI Listing
June 2021

HSF1 promotes endometriosis development and glycolysis by up-regulating PFKFB3 expression.

Reprod Biol Endocrinol 2021 Jun 9;19(1):86. Epub 2021 Jun 9.

Department of Reproductive Medicine, Affiliated Hospital of Weifang Medical University, Weifang, Shandong Province, People's Republic of China.

Background: Endometriosis is a chronic hormonal inflammatory disease characterized by the presence of endometrial tissue outside the uterus. Endometriosis often causes infertility, which brings physical and mental pain to patients and their families.

Methods: We examined the functions of heat shock factor 1 (HSF1) in endometriosis development through cell count assay, cell-scratch assay and clone formation experiments. We used quantitative real-time PCR (qRT-PCR) and Western blot (WB) to detect HSF1 expression. Glucose and lactate levels were determined using a glucose (GO) assay kit and a lactate assay kit. Furthermore, we used a HSF1 inhibitor-KRIBB11 to establish a mouse model of endometriosis.

Results: Our data demonstrated that HSF1 promoted endometriosis development. Interestingly, HSF1 enhanced glycolysis via up-regulating PFKFB3 expression in endometriosis cells, which was a key glycolysis enzyme. Consistently, the HSF1 inhibitor KRIBB11 could abrogate endometriosis progression in vivo and in vitro.

Conclusions: Findings indicate that HSF1 plays an important role in endometriosis development, which might become a new target for the treatment of endometriosis.

Electronic Supplementary Material: Supplementary data are available.
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http://dx.doi.org/10.1186/s12958-021-00770-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188696PMC
June 2021

METTL3 Promotes Esophageal Squamous Cell Carcinoma Metastasis Through Enhancing GLS2 Expression.

Front Oncol 2021 19;11:667451. Epub 2021 May 19.

Clinical Department of Guangdong Metabolic Disease Research Centre of Integrated Chinese and Western Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China.

Recent studies have identified pleiotropic roles of methyltransferase-like 3 (METTL3) in tumor progression. However, the roles of METTL3 in esophageal squamous cell carcinoma (ESCC) are still unclear. Here, we investigated the function and mechanism of METTL3 in ESCC tumorigenesis. We reported that higher METTL3 expression was found in ESCC tissues and was markedly associated with depth of invasion and poor prognosis. Loss- and gain-of function studies showed that METTL3 promoted the migration and invasion of ESCC cells . Integrated methylated RNA immunoprecipitation sequencing (MeRIP-Seq) and RNA sequencing (RNA-Seq) analysis first demonstrated that glutaminase 2 (GLS2) was regulated by METTL3 m6A modification. Our findings identified METTL3/GLS2 signaling as a potential therapeutic target in antimetastatic strategies against ESCC.
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http://dx.doi.org/10.3389/fonc.2021.667451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170325PMC
May 2021

Kaempferol-3-O-Glucuronide Ameliorates Non-Alcoholic Steatohepatitis in High-Cholesterol-Diet-Induced Larval Zebrafish and HepG2 Cell Models via Regulating Oxidation Stress.

Life (Basel) 2021 May 14;11(5). Epub 2021 May 14.

School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.

NAFLD (non-alcoholic fatty liver disease) is one of the most prominent liver diseases in the world. As a metabolic-related disease, the development of NAFLD is closely associated with various degrees of lipid accumulation, oxidation, inflammation, and fibrosis. Ilex chinensis Sims is a form of traditional Chinese medicine which is used to treat bronchitis, burns, pneumonia, ulceration, and chilblains. Kaempferol-3-O-glucuronide (K3O) is a natural chemical present in Ilex chinensis Sims. This study was designed to investigate the antioxidative, fat metabolism-regulating, and anti-inflammatory potential of K3O. A high-cholesterol diet (HCD) was used to establish steatosis in larval zebrafish, whereby 1mM free fatty acid (FFA) was used to induce lipid accumulation in HepG2 cells, while HO was used to induce oxidative stress in HepG2. The results of this experiment showed that K3O reduced lipid accumulation and the level of reactive oxygen species (ROS) both in vivo (K3O, 40 μM) and in vitro (K3O, 20 μM). Additionally, K3O (40 μM) reduced neutrophil aggregation in vivo. K3O (20 μM) also decreased the level of malondialdehyde (MDA) and significantly increased the level of glutathione peroxidase (GSH-px) in both the HCD-induced larval zebrafish model and HO-exposed HepG2 cells. In the mechanism study, , , , and mRNA were all significantly reversed by K3O (20 μM) in zebrafish. Changes in Keap1 and Nrf2 mRNA expression were also detected in HO-exposed HepG2 cells after they were treated with K3O (20 μM). In conclusion, K3O exhibited a reduction in oxidative stress and lipid peroxidation, and this may be related to the Nrf2/Keap1 pathway in the NAFLD larval zebrafish model.
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http://dx.doi.org/10.3390/life11050445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155963PMC
May 2021

Distinct expression requirements and rescue strategies for loss- and gain-of-function mutations.

Elife 2021 Jun 1;10. Epub 2021 Jun 1.

Department of Pharmacology and Physiology, University of Rochester, School of Medicine and Dentistry, Rochester, United States.

Genetic mutation of the human gene, which encodes a Ca-activated Cl channel (BEST1) predominantly expressed in retinal pigment epithelium (RPE), causes a spectrum of retinal degenerative disorders commonly known as bestrophinopathies. Previously, we showed that BEST1 plays an indispensable role in generating Ca-dependent Cl currents in human RPE cells, and the deficiency of BEST1 function in patient-derived RPE is rescuable by gene augmentation (Li et al., 2017). Here, we report that patient-derived loss-of-function and gain-of-function mutations require different mutant to wild-type (WT) molecule ratios for phenotypic manifestation, underlying their distinct epigenetic requirements in bestrophinopathy development, and suggesting that some of the previously classified autosomal dominant mutations actually behave in a dominant-negative manner. Importantly, the strong dominant effect of gain-of-function mutations prohibits the restoration of BEST1-dependent Cl currents in RPE cells by gene augmentation, in contrast to the efficient rescue of loss-of-function mutations via the same approach. Moreover, we demonstrate that gain-of-function mutations are rescuable by a combination of gene augmentation with CRISPR/Cas9-mediated knockdown of endogenous expression, providing a universal treatment strategy for all bestrophinopathy patients regardless of their mutation types.
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http://dx.doi.org/10.7554/eLife.67622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169119PMC
June 2021

Development and Validation of a Nomogram to Predict the Individual Future Stroke Risk for Adult Patients With Moyamoya Disease: A Multicenter Retrospective Cohort Study in China.

Front Neurol 2021 13;12:669025. Epub 2021 May 13.

Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Studies exploring the predictive performance of major risk factors associated with future stroke events are insufficient, and a useful tool to predict individual risk is not available. Therefore, personalized advice for preventing future stroke in patients with moyamoya disease (MMD) cannot provide evidence-based recommendations. The aim of this study was to develop a novel nomogram with reliable validity to predict the individual risk of future stroke for adult MMD patients. This study included 450 patients from seven medical centers between January 2013 and December 2018. Follow-ups were performed via clinical visits and/or telephone interviews from initial discharge to December 2019. The cohort was randomly assigned to a training set (2/3, = 300) for nomogram development and a test set (1/3, = 150) for external validation. The Kaplan-Meier analyses and receiver operating characteristic (ROC) curves were applied to assess the clinical benefits of this nomogram. Diabetes mellitus, a family history of MMD, a past history of stroke or transient ischemic attack, clinical manifestation, and treatment were identified as major risk factors via the least absolute shrinkage and selection operator (LASSO) method. A nomogram including these predictors was established via a multivariate Cox regression model, which displayed excellent discrimination [Harrell's concordance index (C-index), 0.85; 95% confidence interval (CI): 0.75-0.96] and calibration. In the external validation, the nomogram was found to have good discrimination (C-index, 0.81; 95% CI: 0.68-0.94) and calibration. In the subgroup analysis, this predictive nomogram also showed great performance in both ischemic-type (C-index, 0.90; 95% CI: 0.77-1.00) and hemorrhagic-type MMD (C-index, 0.72; 95% CI: 0.61-0.83). Furthermore, the nomogram was shown to have potential in clinical practice through Kaplan-Meier analyses and ROC curves. We developed a novel nomogram incorporating several clinical characteristics with relatively good accuracy, which may have considerable potential for evaluating individual future stroke risk and providing useful management recommendations for adult patients with MMD in clinical practice.
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http://dx.doi.org/10.3389/fneur.2021.669025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155507PMC
May 2021

Pre-supplementary motor network connectivity and clinical outcome of magnetic stimulation in obsessive-compulsive disorder.

Hum Brain Mapp 2021 Aug 29;42(12):3833-3844. Epub 2021 May 29.

Department of Neurology, The First Affiliated Hospital of Anhui Medical University, The School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, China.

A large proportion of patients with obsessive-compulsive disorder (OCD) respond unsatisfactorily to pharmacological and psychological treatments. An alternative novel treatment for these patients is repetitive transcranial magnetic stimulation (rTMS). This study aimed to investigate the underlying neural mechanism of rTMS treatment in OCD patients. A total of 37 patients with OCD were randomized to receive real or sham 1-Hz rTMS (14 days, 30 min/day) over the right pre-supplementary motor area (preSMA). Resting-state functional magnetic resonance imaging data were collected before and after rTMS treatment. The individualized target was defined by a personalized functional connectivity map of the subthalamic nucleus. After treatment, patients in the real group showed a better improvement in the Yale-Brown Obsessive Compulsive Scale than the sham group (F  = 6.0, p = .019). To show the neural mechanism involved, we identified an "ideal target connectivity" before treatment. Leave-one-out cross-validation indicated that this connectivity pattern can significantly predict patients' symptom improvements (r = .60, p = .009). After real treatment, the average connectivity strength of the target network significantly decreased in the real but not in the sham group. This network-level change was cross-validated in three independent datasets. Altogether, these findings suggest that personalized magnetic stimulation on preSMA may alleviate obsessive-compulsive symptoms by decreasing the connectivity strength of the target network.
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http://dx.doi.org/10.1002/hbm.25468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288080PMC
August 2021

A 73-Year-Old Woman With Hyperammonemic Encephalopathy Caused by Noncirrhotic Congenital Portosystemic Shunts.

Neurology 2021 May 26. Epub 2021 May 26.

Department of Neurology, The Third Affiliated Hospital of Chongqing Medical University, 1 Shuanghu Road, Chongqing 401120, China

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http://dx.doi.org/10.1212/WNL.0000000000012274DOI Listing
May 2021

Quantification of Increased Corneal Subbasal Nerve Tortuosity in Dry Eye Disease and Its Correlation With Clinical Parameters.

Transl Vis Sci Technol 2021 05;10(6):26

Department of Ophthalmology, Peking University Third Hospital, Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Beijing, China.

Purpose: This study quantified corneal subbasal nerve tortuosity in dry eye disease (DED) and investigated its correlation with clinical parameters by proposing an aggregated measure of tortuosity (Tagg).

Methods: The sample consisted of 26 eyes of patients with DED and 23 eyes of healthy volunteers, which represented separately the dry eye group and the control group. Clinical evaluation of DED and in vivo confocal microscopy analysis of the central cornea were performed. Tagg incorporated six metrics of tortuosity. Corneal subbasal nerve images of subjects and a validation data set were analyzed using Tagg. Spearman's rank correlation was performed on Tagg and clinical parameters.

Results: Tagg was validated using 1501 corneal nerve images. Tagg was higher in patients with DED than in healthy volunteers (P < 0.001). Tagg was positively correlated with the ocular surface disease index (r = 0.418, P = 0.003) and negatively correlated with tear breakup time (r = -0.398, P = 0.007). There was no correlation between Tagg and visual analog scale scores, corneal fluorescein staining scores, or the Schirmer I test.

Conclusions: Tagg was validated for quantification of corneal subbasal nerve tortuosity and was higher in patients with DED than in healthy volunteers. A higher Tagg may be linked to ocular discomfort, visual function disturbance, and tear film instability.

Translational Relevance: Corneal subbasal nerve tortuosity is a potential biomarker for corneal neurobiology in DED.
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http://dx.doi.org/10.1167/tvst.10.6.26DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142722PMC
May 2021

Antimicrobial peptide 17BIPHE2 inhibits the proliferation of lung cancer cells and by regulating the ERK signaling pathway.

Oncol Lett 2021 Jul 28;22(1):501. Epub 2021 Apr 28.

Department of Laboratory Medicine, College of Clinical Medicine, Shuangyi Campus, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China.

In 2018, there were 18.1 million new cancer cases and 9.6 million cancer-related deaths worldwide, among which the incidence rate of lung cancer (11.6%) and fatality rate (18.4%) both ranked first. The antimicrobial peptide LL-37 is an important component of the natural immune system and possesses several biological properties, including antibacterial, antiviral and anticancer effects. The antimicrobial peptide 17BIPHE2, the shortest synthetic peptide derivative of LL-37, exhibits biological activities similar to those of LL-37. The objective of the present study was to investigate the mechanism of action of exogenous 17BIPHE2 against lung cancer cells. The human lung adenocarcinoma cell line A549 was treated with 17BIPHE2. Changes in cell proliferation, migration, invasion, mitochondrial membrane potential (ΔΨm), and the levels of reactive oxygen species (ROS), Ca and apoptosis-related proteins, including BAX, BCL-2 and ERK, were detected using flow cytometry, transmission electron microscopy and western blotting. The results showed that 17BIPHE2 significantly increased the apoptosis rate of A549 cells and elevated BAX expression, ERK phosphorylation, and ROS and Ca levels, but decreased the expression of BCL-2, ERK and Ki67. In addition, the peptide reduced ΔΨm and the cell migration ability of A549 cells and inhibited tumor growth. ERK inhibition significantly attenuated the anticancer effect of 17BIPHE2. The present observations suggested that 17BIPHE2 can effectively inhibit cancer cells by regulating the ERK signaling pathway.
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http://dx.doi.org/10.3892/ol.2021.12762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108245PMC
July 2021

Analysis of the relationship between geography and body color with the genetic diversity in the Echiura worm based on the mitochondrial and D-loop sequences.

Mitochondrial DNA B Resour 2021 Apr 15;6(4):1380-1386. Epub 2021 Apr 15.

Dalian Modern Agricultural Production Development Service Center, Dalian Aquatic Technology Promotion Station, Dalian, China.

is the only species distributed in Bohai Gulf of China. The wild populations of this species have sharply declined in China due to overfishing. Over 150 samples from Bohai Gulf were collected in the present study, which were classified into five populations according to their geographic areas and body colors. The genetic diversity and population structure of these populations were investigated by mitochondiral and D-loop sequences. The haplotype diversity of based on and D-loop sequences were still high. In addition, the evolution rate of D-loop region could faster than the gene of . Meanwhile, over 99% genetic diversity was contributed by different individuals within populations. Moreover, phylogenetic trees did not show clear geographic or color cluster. Our findings indicated that this species in Bohai Gulf of China should be treated as a whole population.
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http://dx.doi.org/10.1080/23802359.2021.1910082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078999PMC
April 2021

Decision making under ambiguity and risk in adolescent-onset schizophrenia.

BMC Psychiatry 2021 05 4;21(1):230. Epub 2021 May 4.

Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, 230022, China.

Objective: Numerous studies have identified impaired decision making (DM) under both ambiguity and risk in adult patients with schizophrenia. However, the assessment of DM in patients with adolescent-onset schizophrenia (AOS) has been challenging as a result of the instability and heterogeneity of manifestations. The Iowa Gambling Task (IGT) and Game of Dice Task (GDT), which are frequently used to evaluate DM respectively under ambiguity and risk, are sensitive to adolescents and neuropsychiatric patients. Our research intended to examine the performance of DM in a relatively large sample of patients with AOS using the above-mentioned two tasks. We also aimed to take a closer look at the relationship between DM and symptom severity of schizophrenia.

Methods: We compared the performance of DM in 71 patients with AOS and 53 well-matched healthy controls using IGT for DM under ambiguity and GDT for DM under risk through net scores, total scores and feedback ration. Neuropsychological tests were conducted in all participants. Clinical symptoms were evaluated by using Positive and Negative Syndrome Scale (PANSS) in 71 patients with AOS. Pearson's correlation revealed the relationship among total score of DM and clinical and neuropsychological data.

Results: Compared to healthy controls, patients with AOS failed to show learning effect and had a significant difference on the 5th block in IGT and conducted more disadvantageous choices as well as exhibited worse negative feedback rate in GDT. Apart from DM impairment under risk, diminished DM abilities under ambiguity were found related to poor executive function in AOS in the present study.

Conclusions: Our findings unveiled the abnormal pattern of DM in AOS, mainly reflected under the risky condition, extending the knowledge on the performance of DM under ambiguity and risk in AOS. Inefficient DM under risk may account for the lagging impulse control and the combined effects of developmental disease. In addition, our study demonstrated that the performance on IGT was related to executive function in AOS.
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http://dx.doi.org/10.1186/s12888-021-03230-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094464PMC
May 2021

Construction of hyperbranched and pH-responsive polymeric nanocarriers by yne-phenol click-reaction for tumor synergistic chemotherapy.

Colloids Surf B Biointerfaces 2021 Aug 26;204:111790. Epub 2021 Apr 26.

School of Chemistry, MOE Key Laboratory for Non-equilibrium Synthesis and Modulation of Condensed Matter, Xi'an Key Laboratory of Sustainable Energy Material Chemistry, Xi'an Jiaotong University, Xi'an, 710049, PR China; Instrumental Analysis Center, Xi'an Jiaotong University, Xi'an, 710049, PR China. Electronic address:

In past decades, to improve the chemotherapeutic efficiency and reduce the systemic toxicity of small molecule anti-cancer drugs, polymer-based drug delivery systems (DDSs) have attracted great attention for tumor treatment due to their remarkable biocompatibility and responsive degradation in tumor microenvironment (TME). Herein, we developed a kind of pH-responsive and degradable hyperbranched polymeric nanocarriers via yne-phenol click-reaction of resveratrol (RSV) with bifunctional n-butyl dipropiolate (BDP) for efficient doxorubicin (DOX) delivery. The natural product RSV with three phenol groups has excellent antioxidant activity and synergetic enhancement for some anticancer drugs such as DOX. RSV tends to attack the alkynyl groups on BDP by nucleophilic addition in the presence of base as catalyst to afford hyperbranched polyprodrug (denoted as RB). PEGylated RB (termed as RBP) were further synthesized to improve the water solubility and prolong blood circulation by the click reaction of propiolate-terminated RB with amino terminated poly(ethylene glycol) (PEG-NH). Interestingly, the RBP have high DOX loading ratio (∼58.6 %) at neutral pH, but the vinyl-ether bonds in RB could break down at low pH conditions such as acidic TME (extracellular pH∼6.8, endosomes and lysosomes pH∼5.0) that leading to the targeting release of DOX and RSV. Therefore, the developed [email protected] nanoparticles exhibited high kill efficiency to tumor cells and slight damage to normal cells due to the effective delivery and release of DOX and RSV in tumor sites and the synergistic enhancement effect of two drugs.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111790DOI Listing
August 2021

Spatial and environmental characteristics of colloidal trace Cu in the surface water of the Yellow River Estuary, China.

Mar Pollut Bull 2021 Jul 25;168:112401. Epub 2021 Apr 25.

CAS Key Laboratory of Coastal Environmental Processes and Ecological Remediation, Shandong Key Laboratory of Coastal Environmental Processes, Research Center for Coastal Environment Engineering Technology of Shandong Province, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, PR China.

Dynamic variations in chemical composition and size distribution of dissolved copper (Cu) along the river-sea interface in the Yellow River Estuary (China) were investigated. On average, ~64% and ~8% of bulk dissolved Cu (<0.45 μm) were partitioned in the <1 kDa fraction and 1-100 kDa, respectively. The other 28% were in the 100 kDa-0.45 μm colloids, which indicates that this fraction may dominate the overall morphology of colloidal Cu. The <3 kDa Cu fraction was susceptible to environmental parameters and the >3 kDa fraction was related to the behavior of dissolved organic carbon. 1-100 kDa Cu migrated more violently than >100 kDa Cu and tended to be a stable polymer, with stability increasing towards the sea. The source of <1 kDa Cu was complex and may be supplemented by the decomposition of small molecular colloids and the addition of the sediments or particles ligands.
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http://dx.doi.org/10.1016/j.marpolbul.2021.112401DOI Listing
July 2021

Common variants of the autism-associated CNTNAP2 gene contribute to the modulatory effect of social function mediated by temporal cortex.

Behav Brain Res 2021 Jul 24;409:113319. Epub 2021 Apr 24.

Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China; Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, 230022, China; Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health, Hefei, 230022, China; School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, 230022, China; Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, 230022, China. Electronic address:

Autistic traits are highly heritable and characterized by social deficits. Common genetic variants of the autism-related CNTNAP2 gene have been linked with social impairments, but the neural substrates are poorly understood. In the present study, we investigated the genetic effect of common variants of CNTNAP2 (rs2710102 and rs7794745) on gray matter volume and its association with social performance among 442 healthy participants. Our results showed that individuals with rs2710102 GG homozygotes had smaller left superior temporal gyrus (STG)/insular volume than A-allele carriers (AA and AG), while individuals with rs7794745 TT and AT showed smaller right parahippocampal, right STG/insular, and left inferior parietal lobule (IPL) cortex volume than those with rs7794745 AA. Smaller volume of the STG/insular and parahippocampal cortex was associated with poorer social performance. An indirect effect of CNTNAP2 rs7794745 and rs2710102 genotype on the social performance was mediated by the STG/insular cortex and parahippocampal cortex volume. These findings provided insight into the genetic effect of CNTNAP2 variants on social behavior, which may be moderated by the temporal cortex.
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http://dx.doi.org/10.1016/j.bbr.2021.113319DOI Listing
July 2021

Adsorption characteristics and the removal mechanism of two novel Fe-Zn composite modified biochar for Cd(II) in water.

Bioresour Technol 2021 Aug 31;333:125078. Epub 2021 Mar 31.

Innovation Team of Remediation for Heavy Metal Contaminated Farmlands, Agro-Environmental Protection Institute, Ministry of Agriculture, Tianjin 300191, People's Republic of China; Key Laboratory of Original Environmental Pollution Control, Ministry of Agriculture, Agro-Environmental Protection Institute, Ministry of Agriculture, Tianjin 300191, People's Republic of China.

In this study, adsorbents (Fe/Zn-RBC and Fe/Zn-DBC) for the removal of Cd(II) in water were successfully prepared by iron/zinc composite modified biochar derived from the branches of Robinia pseudoacacia biochar (RBC) and durian shells biochar (DBC). The results revealed that the iron and zinc ions were successfully loaded onto the biochar. The adsorption data of Cd(II) on Fe/Zn-BC conformed to the models of pseudo-second-order kinetic, Langmuir isothermal, and Redlich-Paterson. According to the results of batch experiments, the maximum sorption capacities of Fe/Zn-RBC and Fe/Zn-DBC for Cd(II) were approximately five times and three times higher than RBC and DBC, respectively. As the most dominant adsorption mechanisms, Cd(II) and CO, Fe-O, Zn-O, and oxygen-containing functional groups on the Fe/Zn-BC surfaces precipitated CdCO, Cd(OH), and CdO. Therefore, Fe/Zn-BC is an excellent adsorbent that removes Cd(II) from aqueous solutions, and also can be used in waste resource utilization, which has potential applications prospects.
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http://dx.doi.org/10.1016/j.biortech.2021.125078DOI Listing
August 2021

Rapid detection of twenty-nine common Chinese glucose-6-phosphate dehydrogenase variants using a matrix-assisted laser desorption/ionization-time of flight mass spectrometry assay on dried blood spots.

Clin Biochem 2021 Aug 18;94:27-34. Epub 2021 Apr 18.

Department of Pediatric Endocrinology and Genetics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai 200092, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. Electronic address:

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited disease. Current neonatal screening methods for G6PD deficiency primarily rely on the use of biochemical tests. However, only 15%-20% of female carriers were estimated to have been detected using these tests. As a better alternative, DNA-based tests could be used for G6PD deficiency screening. We aimed to develop a matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) assay for G6PD variant detection.

Methods: A MALDI-TOF MS assay with multiprimer extension (multi-PEX) was developed to rapidly and accurately detect the 29 common G6PD variants in the Chinese population using a dried blood spot as a template. A parallel study screening 571 unrelated neonatal samples using the MALDI-TOF MS and fluorescence quantitative enzymatic assays was performed. All results were confirmed by Sanger sequencing in a blind study.

Results: In 571 unrelated neonatal samples, 34 positive samples, including 26 samples from hemizygous males and eight samples from heterozygous females, were correctly identified, yielding a clinical sensitivity of 100%. The results were validated using Sanger sequencing with 100% concordance. In contrast, the fluorescence quantitative enzymatic assay had a 75% false negative and 88.8% false positive rate for the detection of heterozygous G6PD deficient females.

Conclusions: We established a reliable MALDI-TOF MS assay for G6PD deficiency screening in the Chinese population maximizing the chance of detection of heterozygous G6PD deficient females and reducing the false negative and false positive rates associated with routinely used newborn screening procedures.
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http://dx.doi.org/10.1016/j.clinbiochem.2021.04.012DOI Listing
August 2021

Shyness and Adjustment in Early Childhood in Southeast China: The Moderating Role of Conflict Resolution Skills.

Front Psychol 2021 1;12:644652. Epub 2021 Apr 1.

Department of Preschool Education, Shanghai Normal University, Shanghai, China.

The massive social change in urban China today has led to a decline in the adaptive implications of shyness for child adjustment, yet evidence of this trend in young children is limited. Moreover, the underlying mechanisms that help to explain the associations between shyness and maladjustment remains poorly understood. The primary goal of the present study was to explore the moderating role of conflict resolution skills in the links between shyness and socio-emotional and school adjustment among urban Chinese preschoolers. Data were collected from 360 children (44.4% girls, = 4.72 years, = 0.63) in kindergartens using parent ratings, teacher ratings, and child interviews. The analyses indicated that the relations between shyness and adjustment were moderated by child conflict resolution skills, which served to buffer shy children from adjustment problems. The results were discussed in terms of the implications of conflict resolution skills for early adjustment of shy preschoolers in the Chinese context.
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http://dx.doi.org/10.3389/fpsyg.2021.644652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047660PMC
April 2021

Semen quality and windows of susceptibility: A case study during COVID-19 outbreak in China.

Environ Res 2021 06 2;197:111085. Epub 2021 Apr 2.

Department of Environmental Sciences and Engineering, College of Architecture and Environment, Sichuan University, PR China. Electronic address:

Background: To evaluate the impact of air pollution exposure on semen quality parameters during COVID-19 outbreak in China, and to identify potential windows of susceptibility for semen quality.

Methods: A retrospective observational study was carried out on 1991 semen samples collected between November 23, 2019 and July 23, 2020 (a period covering COVID-19 lock-down in China) from 781 sperm donor candidates at University-affiliated Sichuan Provincial Human Sperm Bank. Multivariate mixed-effects regression models were constructed to investigate the relationship between pollution exposure, windows of susceptibility, and semen quality, while controlling for biographic and meteorologic confounders.

Result(s): The results indicated multiple windows of susceptibility for semen quality, especially sperm motility, due to ambient pollution exposure. Exposure to particulate matters (PM and PM), O and NO during late stages of spermatogenesis appeared to have weak but positive association with semen quality. Exposure to CO late in sperm development appeared to have inverse relationship with sperm movement parameters. Exposure to SO appeared to influence semen quality throughout spermatogenesis.

Conclusion(s): Potential windows of susceptibility for semen quality varied depending on air pollutants. Sperm motility was sensitive to pollution exposure. Findings from current study further elucidate the importance of sensitive periods during spermatogenesis and provide new evidence for the determinants of male fertility.
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http://dx.doi.org/10.1016/j.envres.2021.111085DOI Listing
June 2021

Molecular mechanism of RNase R substrate sensitivity for RNA ribose methylation.

Nucleic Acids Res 2021 05;49(8):4738-4749

The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.

RNA 2'-O-methylation is widely distributed and plays important roles in various cellular processes. Mycoplasma genitalium RNase R (MgR), a prokaryotic member of the RNase II/RNB family, is a 3'-5' exoribonuclease and is particularly sensitive to RNA 2'-O-methylation. However, how RNase R interacts with various RNA species and exhibits remarkable sensitivity to substrate 2'-O-methyl modifications remains elusive. Here we report high-resolution crystal structures of MgR in apo form and in complex with various RNA substrates. The structural data together with extensive biochemical analysis quantitively illustrate MgR's ribonuclease activity and significant sensitivity to RNA 2'-O-methylation. Comparison to its related homologs reveals an exquisite mechanism for the recognition and degradation of RNA substrates. Through structural and mutagenesis studies, we identified proline 277 to be responsible for the significant sensitivity of MgR to RNA 2'-O-methylation within the RNase II/RNB family. We also generated several MgR variants with modulated activities. Our work provides a mechanistic understanding of MgR activity that can be harnessed as a powerful RNA analytical tool that will open up a new venue for RNA 2'-O-methylations research in biological and clinical samples.
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http://dx.doi.org/10.1093/nar/gkab202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096214PMC
May 2021

Bispecific c-Met/PD-L1 CAR-T Cells Have Enhanced Therapeutic Effects on Hepatocellular Carcinoma.

Front Oncol 2021 10;11:546586. Epub 2021 Mar 10.

Department of Gastroenterology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.

T cells expressing chimeric antigen receptors, especially CD19 CAR-T cells have exhibited effective antitumor activities in B cell malignancies, but due to several factors such as antigen escape effects and tumor microenvironment, their curative potential in hepatocellular carcinoma has not been encouraging. To reduce the antigen escape risk of hepatocellular carcinoma, this study was to design and construct a bispecific CAR targeting c-Met and PD-L1. c-Met/PD-L1 CAR-T cells were obtained by lentiviral transfection, and the transfection efficiency was monitored by flow cytometry analysis. LDH release assays were used to elucidate the efficacy of c-Met/PD-L1 CAR-T cells on hepatocellular carcinoma cells. In addition, xenograft models bearing human hepatocellular carcinoma were constructed to detect the antitumor effect of c-Met/PD-L1 CAR-T cells . The results shown that this bispecific CAR was manufactured successfully, T cells modified with this bispecific CAR demonstrated improved antitumor activities against c-Met and PD-L1 positive hepatocellular carcinoma cells when compared with those of monovalent c-Met CAR-T cells or PD-L1 CAR-T cells but shown no distinct cytotoxicity on hepatocytes . experiments shown that c-Met/PD-L1 CAR-T cells significantly inhibited tumor growth and improve survival persistence compared with other groups. These results suggested that the design of single-chain, bi-specific c-Met/PD-L1 CAR-T is more effective than that of monovalent c-Met CAR-T for the treatment of hepatocellular carcinoma., and this bi-specific c-Met/PD-L1 CAR is rational and implementable with current T-cell engineering technology.
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http://dx.doi.org/10.3389/fonc.2021.546586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987916PMC
March 2021

REV-ERB in GABAergic neurons controls diurnal hepatic insulin sensitivity.

Nature 2021 Apr 24;592(7856):763-767. Epub 2021 Mar 24.

Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine, Houston, TX, USA.

Systemic insulin sensitivity shows a diurnal rhythm with a peak upon waking. The molecular mechanism that underlies this temporal pattern is unclear. Here we show that the nuclear receptors REV-ERB-α and REV-ERB-β (referred to here as 'REV-ERB') in the GABAergic (γ-aminobutyric acid-producing) neurons in the suprachiasmatic nucleus (SCN) (SCN neurons) control the diurnal rhythm of insulin-mediated suppression of hepatic glucose production in mice, without affecting diurnal eating or locomotor behaviours during regular light-dark cycles. REV-ERB regulates the rhythmic expression of genes that are involved in neurotransmission in the SCN, and modulates the oscillatory firing activity of SCN neurons. Chemogenetic stimulation of SCN neurons at waking leads to glucose intolerance, whereas restoration of the temporal pattern of either SCN neuron firing or REV-ERB expression rescues the time-dependent glucose metabolic phenotype caused by REV-ERB depletion. In individuals with diabetes, an increased level of blood glucose after waking is a defining feature of the 'extended dawn phenomenon'. Patients with type 2 diabetes with the extended dawn phenomenon exhibit a differential temporal pattern of expression of REV-ERB genes compared to patients with type 2 diabetes who do not have the extended dawn phenomenon. These findings provide mechanistic insights into how the central circadian clock regulates the diurnal rhythm of hepatic insulin sensitivity, with implications for our understanding of the extended dawn phenomenon in type 2 diabetes.
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http://dx.doi.org/10.1038/s41586-021-03358-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085086PMC
April 2021
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