Publications by authors named "Zhe Wang"

2,135 Publications

  • Page 1 of 1

A rare case of ectopic ACTH syndrome with rhabdomyolysis.

BMC Endocr Disord 2021 May 10;21(1):98. Epub 2021 May 10.

Department of Endocrinology and Metabolism, The First Affiliated Hospital of Xi'an Jiaotong University, No.277 West Yanta Road, 710061, Xi'an, People's Republic of China.

Background: Manifestations of hypokalaemia in ectopic adrenocorticotropic hormonesyndrome(EAS) vary from mild muscle weakness to life-threatening arrhythmia. Herein, we present a rare case of EAS with concomitant rhabdomyolysis(RM) as a result of intractable hypokalaemia.

Case Presentation: A 64-year-old man was admitted for limb weakness and facial hyperpigmentation for 2 weeks. Lab tests revealed intractable hypokalaemia (lowest at 1.8 mmol/L) and metabolic alkalosis. The diagnosis of RM was based on a creatine kinase(CK)level of 5 times the upper limit. The elevated CK and myohemoglobin (Mb) levels returned to within the normal range after the alleviation of hypokalaemia. The patient was diagnosed with ACTH-dependent Cushing's syndrome (CS) based on unsuppressed serum cortisol after a low-dose dexamethasone suppression test(LDDST) and remarkably elevated ACTH levels. The diagnosis of EAS was made based on the results of a high-dose dexamethasone suppression test(HDDST) and bilateral inferior petrosal sinus sampling(BIPSS). Multiple lymph nodes in the left supraclavicular fossa, right root of neck, mediastinum and bilateral hili of the lung were found with abnormal uptake of Ga-DOTA-NOC. Mediastinoscopic lymph node biopsy was performed. The pathological diagnosis was small-cell and large-cell neuroendocrine carcinoma with positive ACTH staining. The patient was prescribed mifepristone and received one cycle of chemotherapy. The patient could not tolerate subsequent chemotherapy and died of dyscrasia.

Conclusions: RM is a rare complication of EAS with insidious onset and atypical clinical manifestations. Serum potassium levels should be vigilantly monitored to avoid RM in EAS.
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http://dx.doi.org/10.1186/s12902-021-00755-0DOI Listing
May 2021

Agitation Following Severe Traumatic Brain Injury Is a Clinical Sign of Recovery of Consciousness.

Front Surg 2021 21;8:627008. Epub 2021 Apr 21.

Department of Neurological Surgery, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, United States.

Severe traumatic brain injury (sTBI) often results in disorders of consciousness. Patients emerging from coma frequently exhibit aberrant behaviors such as agitation. These non-purposeful combative behaviors can interfere with medical care. Interestingly, agitation is associated with arousal and is often among the first signs of neurological recovery. A better understanding of these behaviors may shed light on the mechanisms driving the return of consciousness in sTBI patients. This study aims to investigate the association between posttraumatic agitation and the recovery of consciousness. A retrospective chart review was conducted in 530 adult patients (29.1% female) admitted to Stony Brook University Hospital between January 2011 and December 2019 with a diagnosis of sTBI and Glasgow Coma Scale (GCS) ≤8. Agitation was defined as a Richmond Agitation Sedation Scale (RASS) > +1, or any documentation of equivalently combative and violent behaviors in daily clinical notes. The ability to follow verbal commands was used to define the recovery of consciousness and was assessed daily. Of 530 total sTBI patients, 308 (58.1%) survived. Agitation was present in 169 of all patients and 162 (52.6%) of surviving patients. A total of 273 patients followed commands, and 159 of them developed agitation. Forty patients developed agitation on hospital arrival whereas 119 developed agitation later during their hospital course. Presence of in-hospital agitation positively correlated with command-following ( = 0.315, < 0.001). The time to develop agitation and time to follow commands showed positive correlation ( = 0.485, < 0.001). These two events occurred within 3 days in 54 (44.6%) patients, within 7 days in 81 (67.8%) patients, and within 14 days in 96 (80.2%) patients. In 71 (59.7%) patients, agitation developed before command-following; in 36 (30.2%) patients, agitation developed after command-following; in 12 (10.1%) patients, agitation developed on the same day as command-following. Posttraumatic agitation in comatose patients following sTBI is temporally associated with the recovery of consciousness. This behavior indicates the potential for recovery of higher neurological functioning. Further studies are required to identify neural correlates of posttraumatic agitation and recovery of consciousness after sTBI.
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http://dx.doi.org/10.3389/fsurg.2021.627008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097005PMC
April 2021

Gut microbiota modulates the inflammatory response and cognitive impairment induced by sleep deprivation.

Mol Psychiatry 2021 May 7. Epub 2021 May 7.

National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, China.

Sleep deprivation (SD) is increasingly common in modern society, which can lead to the dysregulation of inflammatory responses and cognitive impairment, but the mechanisms remain unclear. Emerging evidence suggests that gut microbiota plays a critical role in the pathogenesis and development of inflammatory and psychiatric diseases, possibly via gut microbiota-brain interactions and neuroinflammation. The present study investigated the impact of SD on gut microbiota composition and explored whether alterations of the gut microbiota play a causal role in chronic inflammatory states and cognitive impairment that are induced by SD. We found that SD-induced gut dysbiosis, inflammatory responses, and cognitive impairment in humans. Moreover, the absence of the gut microbiota suppressed inflammatory response and cognitive impairment induced by SD in germ-free (GF) mice. Transplantation of the "SD microbiota" into GF mice activated the Toll-like receptor 4/nuclear factor-κB signaling pathway and impaired cognitive function in the recipient mice. Mice that harbored "SD microbiota" also exhibited increases in neuroinflammation and microglial activity in the hippocampus and medial prefrontal cortex. These findings indicate that gut dysbiosis contributes to both peripheral and central inflammatory processes and cognitive deficits that are induced by SD, which may open avenues for potential interventions that can relieve the detrimental consequences of sleep loss.
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http://dx.doi.org/10.1038/s41380-021-01113-1DOI Listing
May 2021

A NIR laser induced self-healing PDMS/Gold nanoparticles conductive elastomer for wearable sensor.

J Colloid Interface Sci 2021 Apr 27;599:360-369. Epub 2021 Apr 27.

State Key Laboratory Base for Eco-Chemical Engineering, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China.

Self-healing conductive elastomers have been widely used in smart electronic devices, such as wearable sensors. However, nano fillers hinder the flow of polymer segments, which make the development of conductive elastomer with rapid repair and high ductility a challenge. In this work, thioctic acid (TA) was grafted onto amino-modified polysiloxane (PDMS-NH) by dehydration condensation of amino group and carboxyl group. By introducing gold nanoparticles, a dynamic network based on S-Au interaction was constructed. The dynamic gold cross-linking could effectively dissipate the energy exerted by external force and improve the extensibility of conductive elastomer. In addition, S-Au interaction had a good optothermal effect, so that the elastomer rapidly healed under NIR irradiation, and the repair efficiency reached 92%. We further evaluated the performance of the conductive elastomer as a strain sensor. The sample could accurately monitor the bending of human joints and small muscle state changes. This kind of self-healable conductive elastomer based on dynamic S-Au interaction has great potential in the fields of interpersonal interaction and health monitoring.
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http://dx.doi.org/10.1016/j.jcis.2021.04.117DOI Listing
April 2021

Rubioncolin C, a natural naphthohydroquinone dimer isolated from Rubia yunnanensis, inhibits the proliferation and metastasis by inducing ROS-mediated apoptotic and autophagic cell death in triple-negative breast cancer cells.

J Ethnopharmacol 2021 May 4:114184. Epub 2021 May 4.

State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China. Electronic address:

Ethnopharmacological Relevance: Rubia yunnanensis Diels is a traditional Chinese medicine that has diverse pharmacological activities, including antituberculosis, antirheumatism and anticancers. Rubioncolin C (RC), a natural naphthohydroquinone dimer isolated from the roots and rhizomes of R. yunnanensis Diels, has shown potent antitumor activity. However, the antitumor activity and its potential mechanism of RC in triple negative breast cancer (TNBC) cell lines remained unclear.

Aim Of The Study: This study was aim to investigate the anti-proliferation and anti-metastasis activity as well as the potential mechanism of RC on triple-negative breast cancer cells in vitro and in vivo.

Materials And Methods: The sulforhodamine B assay, colony formation assay and cell cycle analysis were used to determine the anti-proliferative activity of RC on TNBC. The anti-metastatic activity in vitro of RC was detected through the scratch wound assay, cell migration and invasion assays and gelatin zymography. The flow cytometry, JC-1, GFP-LC3B plasmid transfection, MDC, Lysotracker red and Carboxy-HDCFDA, DHE, and MitoSOX™ Red staining were performed to investigate the effect of RC on apoptosis, autophagy and ROS level. The apoptosis inhibitor, autophagy inhibitors and ROS inhibitors were used to further verify the antitumor mechanism of RC. The protein levels related with cell cycle, apoptosis, and autophagy were examined with western blotting. In addition, the anti-tumor activity of RC in vivo was assessed in an experimental metastatic model.

Results: In the present study, RC suppressed the proliferation of TNBC cells in a time- and dose-dependent manner via regulating cell cycle. Further experiments showed that RC inhibited the migration and invasion of TNBC cells by downregulating MMPs and inhibiting EMT. Moreover, we demonstrated that RC induced obviously apoptotic and autophagic cell death, activated MAPK signaling pathway and inhibited mTOR/Akt/p70S6K and NF-κB signaling pathways. Furthermore, the excessive ROS was produced after treatment with RC. The antioxygen NAC and GSH could rescue the cell viability and reestablish the ability of cell metastasis, and inhibit the RC-induced apoptosis and autophagy. In a mice lung metastasis model of breast cancer, RC inhibited lung metastasis, and induced autophagy and apoptosis.

Conclusion: These findings clarified the antitumor mechanism of RC on TNBC cell lines and suggested that RC is a key active ingredient for the cancer treatment of R. yunnanensis, which would help RC develop as a new potential chemotherapeutic agent for TNBC treatment.
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http://dx.doi.org/10.1016/j.jep.2021.114184DOI Listing
May 2021

A Prognostic Risk Stratification Model to Identify Potential Population Benefiting From Postmastectomy Radiotherapy in T1-2 Breast Cancer With 1-3 Positive Axillary Lymph Nodes.

Front Oncol 2021 19;11:640268. Epub 2021 Apr 19.

Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Background And Objectives: To establish a prognostic stratification nomogram for T1-2 breast cancer with 1-3 positive lymph nodes to determine which patients can benefit from postmastectomy radiotherapy (PMRT).

Methods: A population-based study was conducted utilizing data collected from the Surveillance, Epidemiology, and End Results database. Chi-square test or Fisher exact test was used to compare the distribution of characteristics. Cox analysis identified significant prognostic factors for survival. A prognostic stratification model was constructed by R software. Propensity score matching was applied to balance characteristics between PMRT cohort and control cohort. Kaplan-Meier method was performed to evaluate the performance of stratification and the benefits of PMRT in the total population and three risk groups.

Results: The overall performance of the nomogram was good (3-year, 5-year, 10-year AUC were 0.75, 0.72 and 0.67, respectively). The nomogram was performed to excellently distinguish low-risk, moderate-risk, and high-risk groups with 10-year overall survival (OS) of 86.9%, 73.7%, and 62.7%, respectively (P<0.001). In the high-risk group, PMRT can significantly better OS with 10-year all-cause mortality reduced by 6.7% (P = 0.027). However, there was no significant survival difference between PMRT cohort and control cohort in low-risk (P=0.49) and moderate-risk groups (P = 0.35).

Conclusion: The current study developed the first prognostic stratification nomogram for T1-2 breast cancer with 1-3 positive axillary lymph nodes and found that patients in the high-risk group may be easier to benefit from PMRT.
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http://dx.doi.org/10.3389/fonc.2021.640268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089395PMC
April 2021

Total flavonoids of Ameliorated Bile Acid Metabolism Dysfunction in Diabetes Mellitus.

Evid Based Complement Alternat Med 2021 12;2021:6675567. Epub 2021 Apr 12.

Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, China.

is one of the common traditional Chinese medicines used to treat diabetes. However, the underlying mechanism is not fully understood. Flavones are a class of active components that have been reported to exert various activities. Existing evidence suggests that flavones from may be pivotal in modulating progression of diabetes. In this study, total flavones from (TFA) were studied to observe its effects on metabolism of bile acids both and . C57BL/6J mice were treated with STZ and high-fat feeding to construct diabetic model, and HepG2 cell line was applied to investigate the influence of TFA on liver cells. We found a serious disturbance of bile acids and lipid metabolism in diabetic mice, and oral administration or cell incubation with TFA significantly reduced the production of total cholesterol (TCHO), total triglyceride, glutamic oxalacetic transaminase (AST), glutamic-pyruvic transaminase (ALT), and low-density lipoprotein (LDL-C), while it increased the level of high-density lipoprotein (HDL-C). The expression of glucose transporter 2 (GLUT2) and cholesterol 7-hydroxylase (CYP7A1) was significantly upregulated on TFA treatment, and FXR and TGR5 play pivotal role in modulating bile acid and lipid metabolism. This study supplied a novel understanding towards the mechanism of on controlling diabetes.
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http://dx.doi.org/10.1155/2021/6675567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057874PMC
April 2021

Porphyran-derived oligosaccharides alleviate NAFLD and related cecal microbiota dysbiosis in mice.

FASEB J 2021 Jun;35(6):e21458

Key Laboratory of Marine Drugs of Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China.

Porphyran and its derivatives possess a variety of biological activities, such as ameliorations of oxidative stress, inflammation, hyperlipemia, and immune deficiencies. In this study, we evaluated the potential efficacy of porphyran-derived oligosaccharides from Porphyra yezoensis (PYOs) in alleviating nonalcoholic fatty liver disease (NAFLD) and preliminarily clarified the underlying mechanism. NAFLD was induced by a high-fat diet for six months in C57BL/6J mice, followed by treatment with PYOs (100 or 300 mg/kg/d) for another six weeks. We found that PYOs reduced hepatic oxidative stress in mice with NAFLD, which plays a critical role in the occurrence and development of NAFLD. In addition, PYOs could markedly decrease lipid accumulation in liver by activating the IRS-1/AKT/GSK-3β signaling pathway and the AMPK signaling pathway in mice with NAFLD. PYOs also apparently relieved the hepatic fibrosis induced by oxidative stress via downregulation of TGF-β and its related proteins, so that liver injury was markedly alleviated. Furthermore, PYOs treatment relieved cecal microbiota dysbiosis (such as increasing the relative abundance of Akkermansia, while decreasing the Helicobacter abundance), which could alleviate oxidative stress, inflammation, and lipid metabolism, and protect the liver to a certain degree. In summary, PYOs treatment remarkably improved NAFLD via a specific molecular mechanism and reshaped the cecal microbiota.
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http://dx.doi.org/10.1096/fj.202000763RRRDOI Listing
June 2021

An Indole-2-Carboxamide Derivative, LG4, Alleviates Diabetic Kidney Disease Through Inhibiting MAPK-Mediated Inflammatory Responses.

J Inflamm Res 2021 27;14:1633-1645. Epub 2021 Apr 27.

Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.

Aim: Elevated inflammatory signaling has been shown to play an important role in diabetic kidney disease (DKD). We previously developed a new anti-inflammatory compound LG4. In the present study, we have tested the hypothesis that LG4 could prevent DKD by suppressing inflammation and identified the underlying mechanism.

Methods: Streptozotocin-induced type 1 diabetic mice were used to develop DKD and evaluate the effects of LG4 against DKD. To identify the potential targets of LG4, biotin-linked LG4 was synthesized and subjected to proteome microarray screening. The cellular mechanism of LG4 was investigated in HG-challenged SV40MES13 cells.

Results: Although LG4 treatment had no effect on the body weight and blood glucose levels, it remarkably reversed the hyperglycemia-induced pathological changes and fibrosis in the kidneys of T1DM mice. Importantly, hyperglycemia-induced renal inflammation evidenced by NF-κB activation and TNFα and IL-6 overexpression was greatly ameliorated with LG4 treatment. Proteosome microarray screening revealed that JNK and ERK were the direct binding proteins of LG4. LG4 significantly reduced HG-induced JNK and ERK phosphorylation and subsequent NF-κB activation in vivo and in vitro. In addition, LG4 did not show further anti-inflammatory effect in HG-challenged mesangial cells with the presence of JNK or ERK inhibitor.

Conclusion: LG4 showed renoprotective activity through inhibiting ERK/JNK-mediated inflammation in diabetic mice, indicating that LG4 may be a therapeutic agent for DKD.
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http://dx.doi.org/10.2147/JIR.S308353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088301PMC
April 2021

Complete genome sequence analysis of a novel coguvirus isolated from Paris polyphylla var. yunnanensis.

Arch Virol 2021 May 4. Epub 2021 May 4.

Key Laboratory for Agricultural Biodiversity for Pest Management of China, Ministry of Education, Yunnan Agricultural University, No. 95, Jinhei Road, Panlong District, Kunming, 650201, Yunnan, China.

A novel negative-stranded (ns) RNA virus tentatively named "Yunnan paris negative-stranded virus" (YPNSV), was isolated from Paris polyphylla var. yunnanensis plants exhibiting leaf chlorosis and mosaic symptoms in Yunnan. Its complete genome sequence was determined using Illumina and Sanger sequencing. YPNSV has a bipartite genome that consists of a negative-stranded (ns) RNA1 encoding the viral RNA-dependent RNA polymerase (RdRp, p251), an ambisense RNA2 coding for the putative movement protein (MP, p46) and nucleocapsid protein (NP, p39), with the two open reading frames separated by a long intergenic region that is rich in A and U. Sequence comparisons showed that the RdRp, MP, and NP of YPNSV are most similar to those of watermelon crinkle leaf-associated virus 2 (WCLaV-2), with 69.1%, 50.4%, and 60.9% amino acid sequence identity, respectively. Phylogenetic analysis based on deduced amino acid sequences of RdRp and NP showed that YPNSV clustered in a clade with coguviruses and that its closest known relative is WCLaV-2. Based on the above results, YPNSV should be regarded as a new member of genus Coguvirus, family Phenuiviridae.
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http://dx.doi.org/10.1007/s00705-021-05087-xDOI Listing
May 2021

General Synthesis of Ordered Mesoporous Carbonaceous Hybrid Nanostructures with Molecularly Dispersed Polyoxometallates.

Angew Chem Int Ed Engl 2021 May 3. Epub 2021 May 3.

Zhejiang University, Department of Chemistry, CHINA.

Hybrid nanomaterials with controlled dimensions, intriguing components and ordered structures have attracted significant attention in nanoscience and technology. Herein, we report a facile and green polyoxometallate (POM)-assisted hydrothermal carbonization strategy for synthesis of carbonaceous hybrid nanomaterials with molecularly dispersed POMs and ordered mesopores. By using various polyoxometallates such as ammonium phosphomolybdate, silicotungstic acid, and phosphotungstic acid, our approach can be generalized to synthesize ordered mesoporous hybrid nanostructures with diverse compositions and morphologies (nanosheet-assembled hierarchical architectures, nanospheres, and nanorods). Moreover, the ordered mesoporous nanosheet-assembled hierarchical hybrids with molecularly dispersed POMs exhibit remarkable catalytic activity toward the dehydration of tert-butanol with the high isobutene selectivity (100 %) and long-term catalytic durability (80 h).
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http://dx.doi.org/10.1002/anie.202104028DOI Listing
May 2021

Targeting CoaBC through Chemical Inhibition of 4'-Phosphopantothenoyl-l-cysteine Synthetase (CoaB) Activity.

ACS Infect Dis 2021 May 3. Epub 2021 May 3.

MRC/NHLS/UCT Molecular Mycobacteriology Research Unit & DST/NRF Centre of Excellence for Biomedical TB Research & Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine and Department of Pathology, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925, South Africa.

Coenzyme A (CoA) is a ubiquitous cofactor present in all living cells and estimated to be required for up to 9% of intracellular enzymatic reactions. (Mtb) relies on its own ability to biosynthesize CoA to meet the needs of the myriad enzymatic reactions that depend on this cofactor for activity. As such, the pathway to CoA biosynthesis is recognized as a potential source of novel tuberculosis drug targets. In prior work, we genetically validated CoaBC as a bactericidal drug target in Mtb and . Here, we describe the identification of compound , a small molecule inhibitor of the 4'-phosphopantothenoyl-l-cysteine synthetase (PPCS; CoaB) domain of the bifunctional Mtb CoaBC, and show that this compound displays on-target activity in Mtb. Compound was found to inhibit CoaBC uncompetitively with respect to 4'-phosphopantothenate, the substrate for the CoaB-catalyzed reaction. Furthermore, metabolomic profiling of wild-type Mtb H37Rv following exposure to compound produced a signature consistent with perturbations in pantothenate and CoA biosynthesis. As the first report of a direct small molecule inhibitor of Mtb CoaBC displaying target-selective whole-cell activity, this study confirms the druggability of CoaBC and chemically validates this target.
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http://dx.doi.org/10.1021/acsinfecdis.0c00904DOI Listing
May 2021

Electro-optically tunable microring laser monolithically integrated on lithium niobate on insulator.

Opt Lett 2021 May;46(9):2127-2130

We demonstrate monolithic integration of an electro-optically (EO) tunable microring laser on lithium niobate on insulator (LNOI) platform. The device is fabricated by photolithography assisted chemo-mechanical etching, and the pump laser is evanescently coupled into the erbium (${\rm{E}}{{\rm{r}}^{3 +}}$)-doped lithium niobate (LN) microring laser using an undoped LN waveguide mounted above the microring. The quality factor of the LN microring resonator is measured as high as ${1.54} \times {{1}}{{{0}}^5}$ at the wavelength of 1542 nm. Lasing action can be observed at a pump power threshold below 3.5 mW using a 980 nm continuous-wave pump laser. Finally, tuning of the laser wavelength is achieved by varying the electric voltage on the microelectrodes fabricated in the vicinity of a microring waveguide, showing an EO coefficient of 0.33 pm/V.
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http://dx.doi.org/10.1364/OL.424996DOI Listing
May 2021

Kaolin-Enhanced Superabsorbent Composites: Synthesis, Characterization and Swelling Behaviors.

Polymers (Basel) 2021 Apr 8;13(8). Epub 2021 Apr 8.

Department of Polymer Materials and Engineering, School of Chemistry and Materials Science, Heilongjiang University, Harbin 150080, China.

One type of low-cost and eco-friendly organic‒inorganic superabsorbent composite (SAPC) was synthesized by free radical polymerization of acrylic acid (AA), starch (ST), sodium alginate (SA) and kaolin (KL) in aqueous solution. The structure and morphology of the SAPC were characterized by Fourier transform infrared spectrometer (FT-IR), scanning electron microscope (SEM), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). The influence of different reaction conditions on water absorption of SAPC, i.e., SA and KL contents, AA neutralization degree (ND), potassium persulfate (KPS) and N, N'-methylenebisacrylamide (MBA) loading were systematically studied. Under the optimal synthesis conditions, very high water absorption of 1200 g/g was achieved. The swelling kinetic mechanism of SAPC was studied by pseudo-second order swelling kinetics model and Ritger‒Peppas model. The performances of SAPC under different environments were tested and results revealed that this new SAPC had excellent swelling capacity, high water retention, good salt tolerance in monovalent salt solution (NaCl solution) and good pH tolerance between 4 and 10.
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http://dx.doi.org/10.3390/polym13081204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068199PMC
April 2021

Effects of Wireless Remote Microphone on Speech Recognition in Noise for Hearing Aid Users in China.

Front Neurosci 2021 12;15:643205. Epub 2021 Apr 12.

Beijing Institute of Otolaryngology, Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

This study was aimed at evaluating improvements in speech-in-noise recognition ability as measured by signal-to-noise ratio (SNR) with the use of wireless remote microphone technology. These microphones transmit digital signals via radio frequency directly to hearing aids and may be a valuable assistive listening device for the hearing-impaired population of Mandarin speakers in China. Twenty-three adults (aged 19-80 years old) and fourteen children (aged 8-17 years old) with bilateral sensorineural hearing loss were recruited. The Mandarin Hearing in Noise Test was used to test speech recognition ability in adult subjects, and the Mandarin Hearing in Noise Test for Children was used for children. The subjects' perceived SNR was measured using sentence recognition ability at three different listening distances of 1.5, 3, and 6 m. At each distance, SNR was obtained under three device settings: hearing aid microphone alone, wireless remote microphone alone, and hearing aid microphone and wireless remote microphone simultaneously. At each test distance, for both adult and pediatric groups, speech-in-noise recognition thresholds were significantly lower with the use of the wireless remote microphone in comparison with the hearing aid microphones alone ( < 0.05), indicating better SNR performance with the wireless remote microphone. Moreover, when the wireless remote microphone was used, test distance had no effect on speech-in-noise recognition for either adults or children. Wireless remote microphone technology can significantly improve speech recognition performance in challenging listening environments for Mandarin speaking hearing aid users in China.
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http://dx.doi.org/10.3389/fnins.2021.643205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072043PMC
April 2021

Total Synthesis of the Proposed Structure of Characellide B.

Org Lett 2021 May 27;23(9):3680-3684. Epub 2021 Apr 27.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

We achieved the total synthesis of the proposed structure of characellide B, a novel lipoglycotripeptide. Comparison of the data for the synthetic compound with those for the natural product indicated some possible errors in the original structural assignment. Furthermore, we synthesized the other four stereoisomers, focusing on the d-Asp-d--Thr fragment, to determine the actual structure of characellide B. Nevertheless, the data for the stereoisomers were not consistent with those for the natural product.
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http://dx.doi.org/10.1021/acs.orglett.1c01066DOI Listing
May 2021

1,3-Diradicals Embedded in Curved Paraphenylene Units: Singlet versus Triplet State and In-Plane Aromaticity.

J Am Chem Soc 2021 Apr 26. Epub 2021 Apr 26.

Department of Chemistry, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8526, Japan.

Curved π-conjugated molecules and open-shell structures have attracted much attention from the perspective of fundamental chemistry, as well as materials science. In this study, the chemistry of 1,3-diradicals (s) embedded in curved cycloparaphenylene (s) structures, -(+3)s ( = 0-5), was investigated to understand the effects of the curvature and system size on the spin-spin interactions and singlet versus triplet state, as well as their unique characteristics such as in-plane aromaticity. A triplet ground state was predicted for the larger 1,3-diradicals, such as the seven- and eight-paraphenylene-unit-containing diradicals - ( = 4) and - ( = 5), by quantum chemical calculations. The smaller-sized diradicals -(+3)s ( = 0-3) were found to possess singlet ground states. Thus, the ground-state spin multiplicity is controlled by the size of the paraphenylene cycle. The size effect on the ground-state spin multiplicity was confirmed by the experimental generation of - in the photochemical denitrogenation of its azo-containing precursor (-). Intriguingly, a unique type of in-plane aromaticity emerged in the smaller-sized singlet states such as S-- ( = 1), as proven by nucleus-independent chemical shift calculations (NICS) and an analysis of the anisotropy of the induced current density (ACID), which demonstrate that homoconjugation between the 1,3-diradical moiety arises because of the curved and distorted bonding system.
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http://dx.doi.org/10.1021/jacs.1c01329DOI Listing
April 2021

Status of Immunotherapy Acceptance in Chinese Patients With Multiple Sclerosis: Analysis of .

Front Neurol 2021 8;12:651511. Epub 2021 Apr 8.

Department of Neurology, Affiliated Zhongshan Hospital, Xiamen University, Xiamen, China.

The prevalence of multiple sclerosis (MS) in China is low, although it has been increasing recently. Owing to the paucity of data on immunotherapy acceptance in the Chinese population, we conducted this study to analyze factors affecting the acceptance of immunotherapy and selection of disease-modifying therapies (DMTs) based on personal and clinical data of patients with MS. In this study, data were obtained from the , which was the first national survey of patients with MS in China. There were 1,212 patients with MS from 31 provinces who were treated at 49 Chinese hospitals over a 4-month period from May 2018 to August 2018, and the patients were asked to complete online questionnaires to assess their understanding of the disease. In general, highly educated patients with frequent relapses were more willing to receive treatment regardless of DMTs or other immunotherapy, and patients with more understanding of the disease opted to be treated. Younger patient population, patients with severe disease course, and those with more symptoms were likely to choose the treatment. Moreover, a higher proportion of women chose to be treated with DMTs than with other immunotherapies. Education status and patient awareness of the disease impact the treatment acceptance in Chinese patients with MS. Therefore, we call for improving the awareness of MS disease and social security to help patients to improve their quality of life.
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http://dx.doi.org/10.3389/fneur.2021.651511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060470PMC
April 2021

Increased detection of circulating tumor DNA by short fragment enrichment.

Transl Lung Cancer Res 2021 Mar;10(3):1501-1511

Department of Laboratory Technology Development, Global Medical Product Center (GMPC), Beijing Novogene Bioinformatics Technology Co., Ltd., Beijing, China.

Background: Circulating cell-free DNA (cfDNA) detection for non-invasive diagnosis requires higher sensitivity and accuracy due to the low circulating tumor DNA (ctDNA) content. Many methods have been developed to improve detection of ctDNA, including ultra-deep sequencing or enrichment of shorter cfDNA fragments, such as those in the range of 90-150 bp.

Methods: Here, we developed a method for single-stranded DNA (ssDNA) library preparation with a large proportion of magnetic beads to enrich the shorter cfDNA fragments. We aimed to determine if this could increase the ctDNA content and thus improve the sensitivity of ctDNA detection by testing the method in blood samples from patients with advanced cancers (non-small cell lung cancers, esophageal squamous cell carcinoma, cholangiocarcinoma, colorectal cancer and liver cancer).

Results: This method was able to obtain shorter cfDNA both in commercial cfDNA references and real world clinical cfDNA samples. Plasmid simulation experiments showed that using a large proportion of magnetic beads to construct the library could obtain more ctDNA derived from shorter-fragment plasmids, which could significantly improve the detection of ctDNA especially in the low-variant allele frequency sample. In real-world clinical samples, this method may be able to increase the opportunity to obtain alteration reads from short fragments, which was important to low frequency detection.

Conclusions: The ssDNA library preparation with large proportion of magnetic beads could increase the opportunity to obtain alteration reads from short fragments, which is crucial for low variant allele frequency detection.
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http://dx.doi.org/10.21037/tlcr-21-180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044499PMC
March 2021

Whole-genome sequencing association analysis of quantitative red blood cell phenotypes: The NHLBI TOPMed program.

Am J Hum Genet 2021 May 21;108(5):874-893. Epub 2021 Apr 21.

Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.

Whole-genome sequencing (WGS), a powerful tool for detecting novel coding and non-coding disease-causing variants, has largely been applied to clinical diagnosis of inherited disorders. Here we leveraged WGS data in up to 62,653 ethnically diverse participants from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program and assessed statistical association of variants with seven red blood cell (RBC) quantitative traits. We discovered 14 single variant-RBC trait associations at 12 genomic loci, which have not been reported previously. Several of the RBC trait-variant associations (RPN1, ELL2, MIDN, HBB, HBA1, PIEZO1, and G6PD) were replicated in independent GWAS datasets imputed to the TOPMed reference panel. Most of these discovered variants are rare/low frequency, and several are observed disproportionately among non-European Ancestry (African, Hispanic/Latino, or East Asian) populations. We identified a 3 bp indel p.Lys2169del (g.88717175_88717177TCT[4]) (common only in the Ashkenazi Jewish population) of PIEZO1, a gene responsible for the Mendelian red cell disorder hereditary xerocytosis (MIM: 194380), associated with higher mean corpuscular hemoglobin concentration (MCHC). In stepwise conditional analysis and in gene-based rare variant aggregated association analysis, we identified several of the variants in HBB, HBA1, TMPRSS6, and G6PD that represent the carrier state for known coding, promoter, or splice site loss-of-function variants that cause inherited RBC disorders. Finally, we applied base and nuclease editing to demonstrate that the sentinel variant rs112097551 (nearest gene RPN1) acts through a cis-regulatory element that exerts long-range control of the gene RUVBL1 which is essential for hematopoiesis. Together, these results demonstrate the utility of WGS in ethnically diverse population-based samples and gene editing for expanding knowledge of the genetic architecture of quantitative hematologic traits and suggest a continuum between complex trait and Mendelian red cell disorders.
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http://dx.doi.org/10.1016/j.ajhg.2021.04.003DOI Listing
May 2021

Sodium Alginate Binders for Bivalency Aqueous Batteries.

ACS Appl Mater Interfaces 2021 May 22;13(17):20681-20688. Epub 2021 Apr 22.

Advanced Institute of Materials Science and School of Chemical Engineering, Changchun University of Technology, Changchun 130012, PR China.

Environmental friendly sodium alginate (SA) cannot be used as a binder in aqueous batteries due to its high solubility in water. A water-insoluble polyvinylidene difluoride (PVDF) binder has been widely applied for an aqueous battery, in which the toxic and expensive organic solvent of -methy-2-pyrrolidone (NMP) is required during the coating process. Herein, we report that the water-soluble SA can be utilized as a binder in aqueous Zn batteries because SA could cross-link with the Zn ion to form a water-insoluble and mechanically super strong binder for electrodes. Aqueous Zn||LiFePO cells are assembled to demonstrate the performance of the SA binder for LiFePO cathodes. Due to the high adhesion strength of cross-linked Zn-SA, LiFePO with the SA binder displays a high capacity retention of 93.7% with a high Coulombic efficiency of nearly 100% after 100 cycles at a 0.2 C rate, while the capacity of LiFePO with the PVDF binder quickly decays to 84.7% after 100 cycles at 0.2 C. In addition, the LiFePO cathode with the SA binder also has smaller redox polarization, faster ion diffusion rate, and more favorable electrochemical kinetics than that with the PVDF binder.
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http://dx.doi.org/10.1021/acsami.1c02995DOI Listing
May 2021

Explicit Metric-Based Multiconcept Multi-Instance Learning With Triplet and Superbag.

IEEE Trans Neural Netw Learn Syst 2021 Apr 21;PP. Epub 2021 Apr 21.

Multi-instance learning (MIL) has garnered considerable attention in recent years due to its favorable performance in various scenarios. Nonetheless, most previous studies have implicitly expressed the correlation between instances and bags. Moreover, the importance of negative instances has been largely overlooked. Hence, we seek to present an explicit and intuitively understandable method that can compensate for these deficiencies. In this article, we creatively introduce a metric-based multiconcept MIL approach based on two aspects. First, the triplet-based bag embedding method identifies instance categories and builds attention weights for every instance explicitly. Accordingly, bag embedding is accomplished under the limitation of weak supervision. Second, the developed instance correlation metric approach in the superbag considers the multiconcept issue to boost the model generalization performance. We have designed a rich variety of experiments to demonstrate the performance of our algorithm. The artificial data experiment reveals the interpretability of the proposed network. The results of the comparison experiment confirm that our method shows favorable performance in multiple tasks. Finally, we illustrate the motivation of the presented method by the ablation experiments.
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http://dx.doi.org/10.1109/TNNLS.2021.3071814DOI Listing
April 2021

ARIH1 signaling promotes anti-tumor immunity by targeting PD-L1 for proteasomal degradation.

Nat Commun 2021 04 20;12(1):2346. Epub 2021 Apr 20.

Department of Biochemistry and Research Center of Clinical Pharmacy of The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.

Cancer expression of PD-L1 suppresses anti-tumor immunity. PD-L1 has emerged as a remarkable therapeutic target. However, the regulation of PD-L1 degradation is not understood. Here, we identify several compounds as inducers of PD-L1 degradation using a high-throughput drug screen. We find EGFR inhibitors promote PD-L1 ubiquitination and proteasomal degradation following GSK3α-mediated phosphorylation of Ser279/Ser283. We identify ARIH1 as the E3 ubiquitin ligase responsible for targeting PD-L1 to degradation. Overexpression of ARIH1 suppresses tumor growth and promotes cytotoxic T cell activation in wild-type, but not in immunocompromised mice, highlighting the role of ARIH1 in anti-tumor immunity. Moreover, combining EGFR inhibitor ES-072 with anti-CTLA4 immunotherapy results in an additive effect on both tumor growth and cytotoxic T cell activation. Our results delineate a mechanism of PD-L1 degradation and cancer escape from immunity via EGFR-GSK3α-ARIH1 signaling and suggest GSK3α and ARIH1 might be potential drug targets to boost anti-tumor immunity and enhance immunotherapies.
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http://dx.doi.org/10.1038/s41467-021-22467-8DOI Listing
April 2021

Whole exome sequencing improves mutation detection in Hailey-Hailey disease.

J Dermatol 2021 Apr 20. Epub 2021 Apr 20.

Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.

Hailey-Hailey disease (HHD) is an autosomal dominant monogenic disease that is defective in the ATP2C1 gene. In previous studies, Sanger sequencing was the main method applied to detect mutations in HHD patients, and no mutations in the ATP2C1 gene were found in 12-55% of those reported. The aim of our study was to carry out whole exome sequencing (WES) for the HHD patients in whom efforts to identify mutations by Sanger sequencing had failed, and to find a new pathogenic gene. WES was performed using genomic DNA from 13 HHD patients and 364 in-house healthy controls. Potential pathogenic mutations were subsequently validated by Sanger sequencing. As a result, eight mutations in the ATP2C1 gene were identified using WES. In the remaining five patients, we found one mutation in the ATP2A2 gene which was the causal gene of Darier's disease. Four patients had no detectable mutations in ATP2C1 and the other ATPase genes. Together with our previous study in 2019, the total mutation rate was calculated to be 47/52 (90.4%). These findings demonstrate that WES is capable of improving the mutation detection sensitivity in HHD compared with Sanger sequencing.
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http://dx.doi.org/10.1111/1346-8138.15828DOI Listing
April 2021

Therapeutic strategies of different HPV status in Head and Neck Squamous Cell Carcinoma.

Int J Biol Sci 2021 10;17(4):1104-1118. Epub 2021 Mar 10.

Department of Medical Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, P. R. China.

Head and neck squamous cell carcinoma (HNSCC) is the 9 most common malignant tumor in the world. Based on the etiology, HNSCC has two main subtypes: human papillomavirus (HPV) -related and HPV-unrelated. HPV-positive HNSCC is more sensitive to treatment with favorable survival. Due to the different biological behaviors, individual therapy is necessary and urgently required to deduce the therapeutic intensity of HPV-positive disease and look for a more effective and toxicity-acceptable regimen for HPV-negative disease. EGFR amplification and PI3K/AKT/mTOR pathway aberrant activation are quite common in HPV-positive HNSCC. Besides, HPV infection alters immune cell infiltrating in HNSCC and encompasses a diverse and heterogeneous landscape with more immune infiltration. On the other hand, the chance of HPV-negative cancers harboring mutation on the P53 gene is significantly higher than that of HPV-positive disease. This review focuses on the updated preclinical and clinical data of HPV-positive and HPV-negative HNSCC and discusses the therapeutic strategies of different HPV status in HNSCC.
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http://dx.doi.org/10.7150/ijbs.58077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040311PMC
March 2021

TSH attenuates fatty acid oxidation in hepatocytes by reducing the mitochondrial distribution of miR-449a/449b-5p/5194.

Mol Cell Endocrinol 2021 Apr 20;530:111280. Epub 2021 Apr 20.

Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Shandong University, Jinan, 250012, China. Electronic address:

The elevated thyroid-stimulating hormone (TSH) levels contribute to the abnormal expression/activity of several key hepatic lipid metabolism enzymes. Although miRNAs have been shown to play key roles in hepatic lipid metabolism and are found in isolated mitochondria, very little is known about the pathological and physiological significance of their mitochondrial distributions in regulating liver lipid metabolism. Here, we found that TSH significantly reduced the distribution of some miRNAs in mitochondria of hepatocytes, especially miR-449a, miR-449b-5p, and miR-5194. These three miRNAs inhibited their target genes PGC1B, ABCD1, ADIPOR1 and the downstream molecule PPARA. These effects synergistically suppressed fatty acid (FA) β-oxidation in mitochondria and peroxisomes and decreased the translocation of cytosolic very long chain fatty acids to peroxisomes, which noticeably reduced FA catabolism and promoted triglyceride accumulation in hepatocytes. This study reveals the functional significance of changed miRNA mitochondrial-cytoplasmic distribution in the regulation of hepatic lipid metabolism.
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http://dx.doi.org/10.1016/j.mce.2021.111280DOI Listing
April 2021

Graphene Oxide Membranes for Tunable Ion Sieving in Acidic Radioactive Waste.

Adv Sci (Weinh) 2021 Apr 18;8(7):2002717. Epub 2021 Feb 18.

Institute of Nuclear and New Energy Technology (INET) Collaborative Innovation Center of Advanced Nuclear Energy Technology Tsinghua University Beijing 100084 P. R. China.

Graphene oxide (GO) membranes with unique nanolayer structure have demonstrated excellent separation capability based on their size-selective effect, but there are few reports on achieving ion-ion separation, because it is difficult to inhibit the swelling effect of GO nano sheets as well as to precisely control the interlayer spacing to a specific value between the sizes of different metal ions. Here, selective separation of uranium from acidic radioactive waste containing multication is achieved through a precise dual-adjustment strategy on . It is found that GO swelling is greatly restricted in highly acidic solution due to protonation effect. Then the interlayer spacing is further precisely reduced to below the diameter of uranyl ion by increasing the oxidation degree of GO. Sieving uranyl ions from other nuclide ions is successfully realized in pH =3-3 mol L nitric acid solutions.
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http://dx.doi.org/10.1002/advs.202002717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025005PMC
April 2021

Efficient combination of Human Papillomavirus Genotyping for the triage of women with Atypical Squamous Cells of Undetermined Significance in Chinese rural population: A population-based study.

J Cancer 2021 14;12(10):2815-2824. Epub 2021 Mar 14.

Department of Obstetrics and Gynecology, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China.

In this prospective, population-based study, we evaluated the utility of high-risk human papillomavirus (HR-HPV) genotyping for triaging women with atypical squamous cells of undetermined significance (ASC-US) in the Chinese rural area. A total of 40,000 women were recruited from rural areas of Shanxi Province, China, between June 2014 and December 2014. Women with Pap results of ASC-US underwent HPV genotyping, colposcopy and histopathological examination. For those with normal cervixes or cervical intraepithelial neoplasia (CIN) 1 on the initial evaluation, a 2-year follow-up study was performed. The reporting rate of ASC-US was 5.76% (2,304/40,000) in the study population. The detection rates of CIN 2 or above (CIN2+) and CIN 3 or above (CIN3+) in women with ASC-US were 7.28% and 1.75%, respectively. HPV 16 (39.53%), HPV 58 (17.83%), and HPV 52 (15.50%) were the three most prevalent HR-HPV genotypes among all women with ASC-US cytology. The five most common HR-HPV genotypes in CIN3+ lesions were HPV16, HPV58, HPV33, HPV31 and HPV18. Compared with the 15 HR-HPV testing, genotyping for a combination of HPV16/18/31/33/58 increased specificity significantly with virtually no loss of sensitivity for detecting CIN2+ and CIN3+ lesions, as well as significantly reduced colposcopy referral rate (23.15% vs 33.70%, p<0.01). In addition, in the 2-year follow-up period, women with infection of HPV16, 18, 31, 33 or 58 genotypes were the most likely population (92%, 23/25) to develop CIN2 lesion. Our results demonstrate that genotyping for a combination of HPV16/18/31/33/58 provides a more efficient and cost-effective model to risk-stratify women with ASC-US in the Chinese rural population.
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http://dx.doi.org/10.7150/jca.55771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040879PMC
March 2021

Up-Regulation of Glycogen Synthesis and Degradation Enzyme Level Maintained Myocardial Glycogen in Huddling Brandt's Voles Under Cool Environments.

Front Physiol 2021 26;12:593129. Epub 2021 Mar 26.

College of Life Sciences, Qufu Normal University, Qufu, China.

Small mammals exhibit limited glucose use and glycogen accumulation during hypothermia. Huddling is a highly evolved cooperative behavioral strategy in social mammals, allowing adaptation to environmental cooling. However, it is not clear whether this behavior affects the utilization of glycogen in cold environments. Here, we studied the effects of huddling on myocardial glycogen content in Brandt's voles () under a mild cold environment (15°C). Results showed that (1) Compared to the control (22°C) group (CON), the number of glycogenosomes more than tripled in the cool separated group (CS) in both males and females; whereas the number of glycogenosomes increased in females but was maintained in males in the cool huddling group (CH). (2) Glycogen synthase (GS) activity in the CS group remained unchanged, whereas glycogen phosphorylase (GYPL) activity decreased, which mediated the accumulation of glycogen content of the CS group. (3) Both GS and GYPL activity increased which may contribute to the stability of glycogen content in CH group. (4) The expression levels of glucose transporters GLUT1 and GLUT4 increased in the CS group, accompanied by an increase in glucose metabolism. These results indicate that the reduced glycogen degradation enzyme level and enhanced glucose transport may lead to an increase in myocardial glycogen content of the separated voles under cool environment; while the up-regulation of glycogen synthesis and degradation enzyme level maintained myocardial glycogen content in the huddling vole.
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http://dx.doi.org/10.3389/fphys.2021.593129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033036PMC
March 2021

Corrigendum to "The efficacy and acceptability of curcumin for the treatment of depression or depressive symptoms: A systematic review and meta-analysis". [Journal of Affective Disorders 282 (2021) 242-251].

J Affect Disord 2021 Apr 6. Epub 2021 Apr 6.

Department of Psychiatry, the First Hospital of China Medical University, 155 Nanjingbei Street, Shenyang, Liaoning, 110001, China. Electronic address:

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http://dx.doi.org/10.1016/j.jad.2021.03.070DOI Listing
April 2021