Publications by authors named "Yi Liu"

4,905 Publications

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New secondary metabolites with immunosuppressive and BChE inhibitory activities from an endophytic fungus Daldinia sp. TJ403-LS1.

Bioorg Chem 2021 Jun 13;114:105091. Epub 2021 Jun 13.

Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China. Electronic address:

Five new acetylenic phenol derivatives (1-4 and 7), one new benzofuran derivative (8), one new naphthol derivative (9), and two known analogues (5 and 6), were isolated and identified from an endophytic fungus Daldinia sp. TJ403-LS1 that was isolated from the medicinally valuable plant Anoectochilus roxburghii. Their structures were elucidated by means of extensive spectroscopic analyses and electronic circular dichroism (ECD) calculations. In addition, compound 1 exhibited remarkable immunosuppressive activity against LPS and anti-CD3/anti-CD28 mAbs activated murine splenocytes proliferation with the same IC values of 0.06 μM and BChE inhibitory activity with an IC value of 6.93 ± 0.71 μM, and compounds 6, 8 and 9 showed excellent BChE inhibitory activity with IC values of 16.00 ± 0.30, 23.33 ± 0.55, and 15.53 ± 0.39 μM, respectively (positive drug neostigmine, IC = 49.60 ± 6.10 μM), highlighting the promising potentials to be designed and developed as immunosuppressive and BChE inhibitory agents.
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http://dx.doi.org/10.1016/j.bioorg.2021.105091DOI Listing
June 2021

Night Temperature Determines the Interannual Yield Variation in Hybrid and Inbred Rice Widely Used in Central China Through Different Effects on Reproductive Growth.

Front Plant Sci 2021 4;12:646168. Epub 2021 Jun 4.

College of Agriculture, Yangtze University, Jingzhou, China.

Interannual variation in grain yield of rice has been observed at both farm and regional scales, which is related to the climate variability. Previous studies focus on predicting the trend of climate change in the future and its potential effects on rice production using climate models; however, field studies are lacking to examine the climatic causes underlying the interannual yield variability for different rice cultivars. Here a 6-year field experiment from 2012 to 2017 was conducted using one hybrid (Yangliangyou6, YLY6) cultivar and one inbred (Huanghuazhan, HHZ) cultivar to determine the climate factors responsible for the interannual yield variation. A significant variation in grain yield was observed for both the inbred and hybrid cultivars across six planting years, and the coefficient of variation for grain yield was 7.3-10.5%. The night temperature (average daily minimum temperature, T) contributed to the yield variability in both cultivars. However, the two cultivars showed different responses to the change in T. The yield variation in HHZ was mainly explained by the effects of T on grain filling percentage and grain weight, while the change in spikelets m in response to T accounted for the yield variability in YLY6. Further analysis found that spikelets m of YLY6 significantly and negatively correlated with T from transplanting to heading. For HHZ, the grain filling percentage and grain weight were significantly affected by T of the week prior to heading and from heading to maturity, respectively. Overall, there were differences in the response mechanism between hybrid and inbred cultivars to high night temperature. These will facilitate the development of climate-resilient cultivars and appropriate management practices to achieve a stable grain yield.
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http://dx.doi.org/10.3389/fpls.2021.646168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212977PMC
June 2021

Gut microbiota and bone metabolism.

FASEB J 2021 Jul;35(7):e21740

Department of Endocrinology and Metabolism, Laboratory of Endocrinology and Metabolism, Rare Disease Center, West China Hospital, Sichuan University, Chengdu, China.

Osteoporosis is the most common metabolic skeletal disease. It is characterized by the deterioration of the skeletal microarchitecture and bone loss, leading to ostealgia, and even bone fractures. Accumulating evidence has indicated that there is an inextricable relationship between the gut microbiota (GM) and bone homeostasis involving host-microbiota crosstalk. Any perturbation of the GM can play an initiating and reinforcing role in disrupting the bone remodeling balance during the development of osteoporosis. Although the GM is known to influence bone metabolism, the mechanisms associated with these effects remain unclear. Herein, we review the current knowledge of how the GM affects bone metabolism in health and disease, summarize the correlation between pathogen-associated molecular patterns of GM structural components and bone metabolism, and discuss the potential mechanisms underlying how GM metabolites regulate bone turnover. Deciphering the complicated relationship between the GM and bone health will provide new insights into the prevention and treatment of osteoporosis.
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http://dx.doi.org/10.1096/fj.202100451RDOI Listing
July 2021

Diagnosis and treatment of pediatric anaplastic lymphoma kinase-positive large B-cell lymphoma: A case report.

World J Clin Cases 2021 Jun;9(17):4268-4278

Beijing Key Laboratory of Pediatric Hematology Oncology, National Discipline of Pediatrics, Ministry of Education, MOE Key Laboratory of Major Diseases in Children, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.

Background: Anaplastic lymphoma kinase-positive (ALK+) large B-cell lymphoma (LBCL) is a rare type of lymphoma with high invasiveness and rapid progression. It occurs in all age groups, but is extremely rare in children. The lesions mainly involve the lymph nodes and may present with extra-nodal involvement. Response to conventional chemotherapies and local radiotherapy is poor, with a 5-year overall survival of less than 40%. Recently, the use of ALK inhibitors for the treatment of this disease has been reported.

Case Summary: We present a case of a 12-year-old boy diagnosed with ALK+LBCL. The patient had a 2-mo medical history of a calvarial mass, extensive systemic involvement, and positive bone marrow ( fusion gene. Complete remission 1 (CR1) was achieved using the modified LMB89 Group C regimen followed by autologous stem cell transplantation. The patient relapsed 3 mo later. He then achieved CR2 with three short courses of chemotherapy (COP, reduced-dose ICE, low-dose Ara-c+VP16) and continuous alectinib targeted therapy. Afterward, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed. At 16 mo after the allo-HSCT, the patient was still in CR2.

Conclusion: The modified LMB89 Group C regimen and ALK inhibitors are effective. Allo-HSCT should be performed after remission.
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http://dx.doi.org/10.12998/wjcc.v9.i17.4268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173411PMC
June 2021

Safety evaluation of a food enzyme containing trypsin and chymotrypsin from porcine pancreas.

EFSA J 2021 Jun 16;19(6):e06640. Epub 2021 Jun 16.

The food enzyme is a serine protease complex containing trypsin (EC 3.4.21.4) and chymotrypsin (EC 3.4.21.1) obtained from porcine pancreas by Paninkret Chem.-Pharm. Werk GmbH. The food enzyme is currently only used in protein processing to hydrolyse milk proteins. Milk protein hydrolysates and peptides are mainly used in formulae intended to have reduced allergenicity. Based on the recommended use level and the high consumption of formulae in very young babies, dietary exposure to the food enzyme-total organic solids (TOS) was estimated to be 180 mg TOS/kg body weight (bw) per day for infants and toddlers. Toxicological evaluation was based on the available clinical studies with pancreatic enzymes. Hypersensitivity to the product was identified as the major side effect. However, the intact enzymes are inactivated during preparation of food products; therefore, the Panel considered that the likelihood of adverse effects of the intact enzyme to occur is low. The Panel considered that a risk of allergic sensitisation to these protein hydrolysates after consumption cannot be excluded, but the likelihood of occurrence was considered to be low. Based on the origin of the food enzyme from edible parts of animals, the data provided and the evaluation of clinical studies with pancreatic enzymes and the estimated dietary exposure, the Panel concluded that the food enzyme does not give rise to safety concerns when used in the production of infant formulae based on milk protein hydrolysates.
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http://dx.doi.org/10.2903/j.efsa.2021.6640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207344PMC
June 2021

Safety evaluation of the food enzyme containing chymosin and pepsin from the abomasum of calves and cows.

EFSA J 2021 Jun 9;19(6):e06636. Epub 2021 Jun 9.

The food enzyme containing chymosin (EC 3.4.23.4) and pepsin (EC 3.4.23.1) is produced from the abomasum of purchased from different rennet manufacturers by Laboratorios Arroyo S.A. The food enzyme is intended to be used in milk processing for cheese production. As no concerns arise from the source of the food enzyme, from its manufacture, and based on the history of safe use and consumption, the Panel considered that toxicological data were not required, and no exposure assessment was necessary. On the basis of literature data, the Panel considered that, under the intended conditions of use, the risk of allergic sensitisation and elicitation reactions by dietary exposure could not be excluded, but the likelihood for this to occur was considered to be low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.
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http://dx.doi.org/10.2903/j.efsa.2021.6636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188397PMC
June 2021

Safety evaluation of the food enzyme β-amylase from strain AE-BAF.

EFSA J 2021 Jun 9;19(6):e06635. Epub 2021 Jun 9.

The food enzyme β-amylase (4-α-d-glucan maltohydrolase, EC 3.2.1.2) is produced with the non-genetically modified strain AE-BAF by Amano Enzyme Inc. The production strain has been shown to qualify for Qualified Presumption of Safety (QPS) status. The food enzyme is intended to be used in baking and brewing processes, and in starch processing for the production of glucose syrups and other starch hydrolysates. Since residual amounts of total organic solids (TOS) are removed by the purification steps applied during the production of glucose syrups, dietary exposure was not calculated for this food process. Based on the maximum use levels recommended by the applicant for the baking and brewing processes and individual data from the EFSA Comprehensive European Food Database, dietary exposure was estimated to be up to 2 mg TOS/kg body weight (bw) per day in European populations. Toxicological studies were not considered necessary given the QPS status of the production strain and the nature of the manufacturing process. Similarity of the amino acid sequence to those of known allergens was searched and no match was found. The Panel considered that, under the intended conditions of use, the risk of allergic sensitisation and elicitation reactions by dietary exposure cannot be excluded, but the likelihood for this to occur is considered to be low. Based on the data provided, in particular, the QPS status of the production strain and that no issues of concern arose from the production process, the Panel concluded that the food enzyme β-amylase produced with strain AE-BAF does not give rise to safety concerns under the intended conditions of use.
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http://dx.doi.org/10.2903/j.efsa.2021.6635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189229PMC
June 2021

Cortical Pathways or Mechanism in the Face Inversion Effect in Patients with First-Episode Schizophrenia.

Neuropsychiatr Dis Treat 2021 10;17:1893-1906. Epub 2021 Jun 10.

Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, Guangdong, 510370, People's Republic of China.

Objective: Impaired face perception is considered as a hallmark of social disability in schizophrenia. It is widely believed that inverted faces and upright faces are processed by distinct mechanisms. Previous studies have identified that individuals with schizophrenia display poorer face processing than controls. However, the mechanisms underlying the face inversion effect (FIE) in patients with first-episode schizophrenia (FSZ) remain unclear.

Methods: We designed an fMRI task to investigate the FIE mechanism in patients with schizophrenia. Thirty-four patients with FSZ and thirty-five healthy controls (CON) underwent task-related fMRI scanning, clinical assessment, anhedonia experience examination, and social function and cognitive function evaluation.

Results: The patients with FSZ exhibited distinct functional activity regarding upright and inverted face processing within the cortical face and non-face network. These results suggest that the differences in quantitative processing might mediate the FIE in schizophrenia. Compared with controls, affected patients showed impairments in processing both upright and inverted faces; and for these patients with FSZ, upright face processing was associated with more severe and broader impairment than inverted face processing. Reduced response in the left middle occipital gyrus for upright face processing was related to poorer performance of social function outcomes evaluated using the Personal and Social Performance Scale.

Conclusion: Our data suggested that patients with FSZ exhibited similar performance in processing inverted faces and upright faces, but were less efficient than controls; and for these patients, inverted faces are processed less efficiently than upright faces. We also provided a clue that the mechanism under abnormal FIE might be related to an aberrant activation of non-face-selective areas instead of abnormal activation of face-specific areas in patients with schizophrenia. Finally, our study indicated that the neural pathway for upright recognition might be relevant in determining the functional outcomes of this devastating disorder.
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http://dx.doi.org/10.2147/NDT.S302584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203188PMC
June 2021

Characterization of volatile compounds of Pixian Douban fermented in closed system of gradient steady-state temperature field.

Food Sci Nutr 2021 Jun 29;9(6):2862-2876. Epub 2021 Mar 29.

College of Food and Bioengineering Xihua University Chengdu China.

As an essential flavor condiment in Sichuan cuisine, Pixian Douban (PXDB) is usually produced by open fermentation process in strip pools or ceramic vats. In this study, an experiment of PXDB fermentation was conducted for 90 days in a closed system of gradient steady-state temperature field (GSTF). To investigate the characterization of volatile compounds of PXDB in the closed system, the volatiles in three kinds of samples including samples of GSTF (SGT), samples of constant temperature (SCT), and samples of traditional fermentation (STF) were analyzed. The results showed that 75, 67, and 68 volatile compounds were detected in SGT, SCT, and STF, respectively. Compared with the traditional fermentation, the process in the closed system of GSTF was conducive to produce more kinds of esters and alcohols. A total of 22 major aroma active compounds were identified in three samples by combination analyses of gas chromatography-olfactometry (GC-O) and odor activity value (OAV). The appearance, smell, texture, and taste of the three different samples had shown different changes, but the sensory characteristics of the SGT were more similar to those of the STF by quantitative descriptive analysis (QDA) and principal component analysis (PCA). This study indicated that the closed system of GSTF could be applied in PXDB fermentation to obtain higher quality products, which brought a bright prospect of replacing the traditional fermentation process to realize the controllable industrialized production of PXDB.
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http://dx.doi.org/10.1002/fsn3.2242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194942PMC
June 2021

Safety evaluation of the food enzyme maltogenic α-amylase from the genetically modified strain ROM.

EFSA J 2021 Jun 11;19(6):e06634. Epub 2021 Jun 11.

The food enzyme maltogenic α-amylase (glucan 1,4-α-maltohydrolase; EC 3.2.1.133) is produced with the genetically modified strain ROM by DSM Food Specialities B.V. The genetic modifications do not give rise to safety concerns. The maltogenic α-amylase is considered free from viable cells of the production organism and its recombinant DNA. The food enzyme is intended to be used in baking processes. Based on the maximum use levels recommended for the baking processes and individual data from the EFSA Comprehensive European Food Database, dietary exposure to the food enzyme-total organic solids (TOS) was estimated to be up to 0.065 mg TOS/kg body weight (bw) per day. As the production strain of ROM qualifies for the Qualified Presumption of Safety approach to safety assessment and no issue of concern arose from the production process, no toxicological data are required. Similarity of the amino acid sequence of the food enzyme to those of known allergens was searched and six matches were found. The Panel considered that under the intended conditions of use, the risk of allergic sensitisation and elicitation reactions by dietary exposure cannot be excluded, but the likelihood for this to occur is considered to be low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.
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http://dx.doi.org/10.2903/j.efsa.2021.6634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193509PMC
June 2021

Safety evaluation of the food enzyme containing chymosin and pepsin from the abomasum of suckling lambs and goats.

EFSA J 2021 Jun 10;19(6):e06633. Epub 2021 Jun 10.

The food enzyme containing chymosin (EC 3.4.23.4) and pepsin (EC 3.4.23.1) is derived from the abomasum of suckling lambs and goats by Caporal Enzymes, S.L. The food enzyme is intended to be used in milk processing for cheese production. As no concerns arise from the animal source of the food enzyme, from its manufacture, and based on the history of safe use and consumption, the Panel considered that toxicological data were not required and no exposure assessment was necessary. On the basis of literature data, the Panel considered that, under the intended conditions of use, the risk of allergic sensitisation and elicitation reactions by dietary exposure could not be excluded, but the likelihood for this to occur was considered to be low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.
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http://dx.doi.org/10.2903/j.efsa.2021.6633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190676PMC
June 2021

OGA is associated with deglycosylation of NONO and the KU complex during DNA damage repair.

Cell Death Dis 2021 Jun 16;12(7):622. Epub 2021 Jun 16.

School of Life Sciences, Institute of Life Sciences and Green Development, Hebei University, Baoding, Hebei Province, 071002, China.

Accumulated evidence shows that OGT-mediated O-GlcNAcylation plays an important role in response to DNA damage repair. However, it is unclear if the "eraser" O-GlcNAcase (OGA) participates in this cellular process. Here, we examined the molecular mechanisms and biological functions of OGA in DNA damage repair, and found that OGA was recruited to the sites of DNA damage and mediated deglycosylation following DNA damage. The recruitment of OGA to DNA lesions is mediated by O-GlcNAcylation events. Moreover, we have dissected OGA using deletion mutants and found that C-terminal truncated OGA including the pseudo HAT domain was required for the recruitment of OGA to DNA lesions. Using unbiased protein affinity purification, we found that the pseudo HAT domain was associated with DNA repair factors including NONO and the Ku70/80 complex. Following DNA damage, both NONO and the Ku70/80 complex were O-GlcNAcylated by OGT. The pseudo HAT domain was required to recognize NONO and the Ku70/80 complex for their deglycosylation. Suppression of the deglycosylation prolonged the retention of NONO at DNA lesions and delayed NONO degradation on the chromatin, which impaired non-homologus end joining (NHEJ). Collectively, our study reveals that OGA-mediated deglycosylation plays a key role in DNA damage repair.
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http://dx.doi.org/10.1038/s41419-021-03910-6DOI Listing
June 2021

Differential diagnosis of uncommon prostate diseases: combining mpMRI and clinical information.

Insights Imaging 2021 Jun 16;12(1):79. Epub 2021 Jun 16.

Department of Radiology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, China.

The differential diagnosis of abnormalities in the prostate is broad, covering common (acinar adenocarcinoma, benign prostatic hyperplasia, chronic prostatitis, hemorrhage, cysts, calcifications, atrophy and fibrosis) and less common conditions (tumors other than acinar adenocarcinoma, granulomatous prostatitis containing tuberculosis, abscesses and other conditions, and idiopathic disorders such as amyloidosis and exophytic benign prostatic hyperplasia). Recent advances in magnetic resonance imaging (MRI) of the prostate gland and imaging guidelines, such as the Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1), have dramatically improved the ability to distinguish common abnormalities, especially the ability to detect clinically significant prostate cancer (csPCa). Overlap can exist in the clinical history and imaging features associated with various common/uncommon prostate abnormalities, and biopsy is often required but is invasive. Prostate abnormalities can be divided into two categories: category 1, diseases for which PI-RADS scores are suitable for use, and category 2, diseases for which PI-RADS scores are unsuitable for use. Radiologists must have an intimate knowledge of other diseases, especially uncommon conditions. Past relevant history, symptoms, age, serum prostate-specific antigen (PSA) levels, MRI manifestations, and the applicability of the PI-RADS assessment should be considered when diagnosing prostate abnormalities.
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http://dx.doi.org/10.1186/s13244-021-01024-3DOI Listing
June 2021

CleftNet: Augmented Deep Learning for Synaptic Cleft Detection from Brain Electron Microscopy.

Authors:
Yi Liu Shuiwang Ji

IEEE Trans Med Imaging 2021 Jun 15;PP. Epub 2021 Jun 15.

Detecting synaptic clefts is a crucial step to investigate the biological function of synapses. The volume electron microscopy (EM) allows the identification of synaptic clefts by photoing EM images with high resolution and fine details. Machine learning approaches have been employed to automatically predict synaptic clefts from EM images. In this work, we propose a novel and augmented deep learning model, known as CleftNet, for improving synaptic cleft detection from brain EM images. We first propose two novel network components, known as the feature augmentor and the label augmentor, for augmenting features and labels to improve cleft representations. The feature augmentor can fuse global information from inputs and learn common morphological patterns in clefts, leading to augmented cleft features. In addition, it can generate outputs with varying dimensions, making it flexible to be integrated in any deep network. The proposed label augmentor augments the label of each voxel from a value to a vector, which contains both the segmentation label and boundary label. This allows the network to learn important shape information and to produce more informative cleft representations. Based on the proposed feature augmentor and label augmentor, We build the CleftNet as a U-Net like network. The effectiveness of our methods is evaluated on both external and internal tasks. Our CleftNet currently ranks #1 on the external task of the CREMI open challenge. In addition, both quantitative and qualitative results in the internal tasks show that our method outperforms the baseline approaches significantly.
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http://dx.doi.org/10.1109/TMI.2021.3089547DOI Listing
June 2021

Genetic architecture of 11 organ traits derived from abdominal MRI using deep learning.

Elife 2021 Jun 15;10. Epub 2021 Jun 15.

Calico Life Sciences LLC, South San Francisco, United States.

Cardiometabolic diseases are an increasing global health burden. While socioeconomic, environmental, behavioural, and genetic risk factors have been identified, a better understanding of the underlying mechanisms is required to develop more effective interventions. Magnetic resonance imaging (MRI) has been used to assess organ health, but biobank-scale studies are still in their infancy. Using over 38,000 abdominal MRI scans in the UK Biobank, we used deep learning to quantify volume, fat, and iron in seven organs and tissues, and demonstrate that imaging-derived phenotypes reflect health status. We show that these traits have a substantial heritable component (8-44%) and identify 93 independent genome-wide significant associations, including four associations with liver traits that have not previously been reported. Our work demonstrates the tractability of deep learning to systematically quantify health parameters from high-throughput MRI across a range of organs and tissues, and use the largest-ever study of its kind to generate new insights into the genetic architecture of these traits.
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http://dx.doi.org/10.7554/eLife.65554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205492PMC
June 2021

Antiviral effects of ergosterol peroxide in a pig model of porcine deltacoronavirus (PDCoV) infection involves modulation of apoptosis and tight junction in the small intestine.

Vet Res 2021 Jun 14;52(1):86. Epub 2021 Jun 14.

College of Veterinary Medicine, China Agricultural University, Beijing, China.

Porcine deltacoronavirus (PDCoV) is a newly discovered swine enteropathogenic coronavirus with worldwide distribution. However, efficient strategies to prevent or treat the infection remain elusive. Our in vitro study revealed that ergosterol peroxide (EP) from the mushroom Cryptoporus volvatus has efficient anti-PDCoV properties. The aim of this study is to evaluate the potential of EP as a treatment for PDCoV in vivo and elucidate the possible mechanisms. Seven-day-old piglets were infected with PDCoV by oral administration in the presence or absence of EP. Piglets infected with PDCoV were most affected, whereas administration of EP reduced diarrhea incidence, alleviated intestinal lesion, and decreased viral load in feces and tissues. EP reduced PDCoV-induced apoptosis and enhanced tight junction protein expressions in the small intestine, maintaining the integrity of the intestinal barrier. EP showed immunomodulatory effect by suppressing PDCoV-induced pro-inflammatory cytokines and the activation of IκBα and NF-κB p65, and upregulating IFN-I expression. Knockdown of p38 inhibited PDCoV replication and alleviated PDCoV-induced apoptosis, implying that EP inhibited PDCoV replication and alleviated PDCoV-induced apoptosis via p38/MAPK signaling pathway. Collectively, ergosterol peroxide can protect piglets from PDCoV, revealing the potential of EP for development as a promising strategy for treating and controlling the infection of PDCoV.
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http://dx.doi.org/10.1186/s13567-021-00955-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201433PMC
June 2021

The lncRNA PAHRF functions as a competing endogenous RNA to regulate MST1 expression by sponging miR-23a-3p in pulmonary arterial hypertension.

Vascul Pharmacol 2021 Jun 11:106886. Epub 2021 Jun 11.

Department of Pharmacy, The First People's Hospital of Lianyungang, Lianyungang 222061, China; Department of Pharmacy, The Affiliated Lianyungang Hospital of Xuzhou Medical University/The First People's Hospital of Lianyungang, Lianyungang 222061, China.

Background: Emerging evidence has shown that long non-coding RNA (lncRNA) plays important roles in the development of pulmonary arterial hypertension (PAH). However, some new lncRNAs in patients with PAH are still lacking research. Herein, we examined the expression and role of lncRNA (pulmonary arterial hypertension related factor, PAHRF) in PAH.

Methods: LncRNA PAHRF expression and localization were analyzed by realtime PCR and fluorescence in situ hybridization. Proliferation and apoptosis were detected by MTT, CCK-8, EDU staining, JC-1 assay, flow cytometry and western blotting. Luciferase activity assay was used to identify PAHRF/ miR-23a-3p/serine/threonine kinase 4 (STK4/MST1) interaction.

Results: LncRNA PAHRF was down-regulated in both the PAs of PAH patients and hypoxic human pulmonary artery smooth muscle cells (PASMCs). The overexpression of PAHRF inhibited the proliferation and promoted the apoptosis of PASMCs. Similarly, we also found PAHRF overexpression decreased the proliferation under hypoxia condition. Knockdown of PAHRF exerted the opposite effects. Luciferase activity assay proved molecular binding between PAHRF and hsa-miR-23a-3p. Moreover, MST1 was confirmed to be the putative target gene and regulated by PAHRF/miR-23a-3p. In addition, we explored the molecular mechanism regulating the expression of miR-23a-3p, and found that lncRNA PAHRF acted as an endogenous sponge for miR-23a-3p, and silencing lncRNA PAHRF could up-regulate the expression of miR-23a-3p. On the contrary, PAHRF-overexpressing plasmid inhibited the expression of miR-23a-3p in hypoxia.

Conclusions: Our present study reveals a novel PAH regulating model that is composed of PAHRF, miR-23a-3p, and MST1. The aim of this study is probably going to provide a new explanation and give a further understanding of the occurrence of vascular remodeling in PAH from the perspective competing endogenous RNA hypothesis.
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http://dx.doi.org/10.1016/j.vph.2021.106886DOI Listing
June 2021

Metabolomics in infectious diseases and drug discovery.

Mol Omics 2021 Jun;17(3):376-393

MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London, UK.

Metabolomics has emerged as an invaluable tool that can be used along with genomics, transcriptomics and proteomics to understand host-pathogen interactions at small-molecule levels. Metabolomics has been used to study a variety of infectious diseases and applications. The most common application of metabolomics is for prognostic and diagnostic purposes, specifically the screening of disease-specific biomarkers by either NMR-based or mass spectrometry-based metabolomics. In addition, metabolomics is of great significance for the discovery of druggable metabolic enzymes and/or metabolic regulators through the use of state-of-the-art flux analysis, for example, via the elucidation of metabolic mechanisms. This review discusses the application of metabolomics technologies to biomarker screening, the discovery of drug targets in infectious diseases such as viral, bacterial and parasite infections and immunometabolomics, highlights the challenges associated with accessing metabolite compartmentalization and discusses the available tools for determining local metabolite concentrations.
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http://dx.doi.org/10.1039/d1mo00017aDOI Listing
June 2021

Correction: Direct synthesis of the organic and Ge free Al containing BOG zeolite (ITQ-47) and its application for transformation of biomass derived molecules.

Chem Sci 2020 Nov 5;11(44):12221. Epub 2020 Nov 5.

Instituto de Tecnología Química, Universitat Politècnica de València-Consejo Superior de Investigaciones Científicas Avenida de los Naranjos s/n 46022 Valencia Spain

[This corrects the article DOI: 10.1039/D0SC04044D.].
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http://dx.doi.org/10.1039/d0sc90248aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162468PMC
November 2020

Direct synthesis of the organic and Ge free Al containing BOG zeolite (ITQ-47) and its application for transformation of biomass derived molecules.

Chem Sci 2020 Oct 20;11(44):12103-12108. Epub 2020 Oct 20.

Instituto de Tecnología Química, Universitat Politècnica de València-Consejo Superior de Investigaciones Científicas Avenida de los Naranjos s/n 46022 Valencia Spain

Aluminosilicate boggsite (Si/Al-BOG) has been hydrothermally synthesized without adding organic structure-directing agents (OSDAs) in the synthesis gel using the borosilicogermanium ITQ-47 (Si/B-ITQ-47) zeolite as seeds. The introduction of the costly and environmentally less benign phosphazene organic structure-directing agent is not required to grow the zeolite. Physicochemical characterization experiments show that Si/Al-BOG has good crystallinity, high surface area, tetrahedral Al species, and acid sites. In order to test the catalytic performance of the zeolite, the synthesis of l,l-lactide from l-lactic acid was performed. Si/Al-BOG exhibits 88.2% conversion of l-lactic acid and 83.8% l,l-lactide selectivity, which are better than those of other zeolites studied up to now.
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http://dx.doi.org/10.1039/d0sc04044dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162478PMC
October 2020

Palladium catalyzed carbonylative generation of potent, pyridine-based acylating electrophiles for the functionalization of arenes to ketones.

Chem Sci 2020 Jul 28;11(32):8610-8616. Epub 2020 Jul 28.

Department of Chemistry, McGill University 801 Sherbrooke Street West Montreal QC H3A 0B8 Canada

We describe here the design of a palladium catalyzed route to generate aryl ketones the carbonylative coupling of (hetero)arenes and aryl- or vinyl-triflates. In this, the use of the large bite angle Xantphos ligand on palladium provides a unique avenue to balance the activation of the relatively strong C(sp)-OTf bond with the ultimate elimination of a new class of potent Friedel-Crafts acylating agent: -acyl pyridinium salts. The latter can be exploited to modulate reactivity and selectivity in carbonylative arene functionalization chemistry, and allow the efficient synthesis of ketones with a diverse array of (hetero)arenes.
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http://dx.doi.org/10.1039/d0sc03129aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163404PMC
July 2020

Could neoadjuvant chemotherapy increase postoperative complication risk of laparoscopic total gastrectomy? A mono-institutional propensity score-matched study in China.

World J Gastrointest Surg 2021 May;13(5):429-442

Department of General Surgery, Institute of General Surgery, Chinese PLA General Hospital, Beijing 100853, China.

Background: The potential survival benefit of neoadjuvant chemotherapy (NC) in patients with advanced gastric cancer has been widely recognized. With the development of minimally invasive surgery, which is represented by laparoscopy, the effect of NC on the safety of laparoscopic gastrectomy remains to be further explored.

Aim: To compare the short-term outcomes of laparoscopic total gastrectomy (LTG) after NC (NC-LTG) with LTG alone.

Methods: A total of 92 patients who underwent NC-LTG and 381 patients who received LTG alone at the Chinese PLA General Hospital between September 2015 and September 2020 were retrospectively included in our study. We used propensity-score matching (PSM) to balance baseline bias. After 1:1 PSM, 73 patients were included in each group with no statistically significant difference in baseline characteristics.

Results: The NC-LTG group exhibited a longer operation time (244.10 ± 48.13 min 225.74 ± 45.33 min, = 0.019) and increased intraoperative blood loss [150 (100-300) mL 100 (100-200) mL, = 0.011] compared to the LTG group. The 30-d postoperative morbidity of the NC-LTG group was 20.5% (15/73), and that of the LTG group was 13.7% (10/73). There were no significant differences in 30-d severe complication rates or anastomotic leakage rates. Subgroup analysis showed that the patients with pTNM (pathological tumor-node-metastasis classification) T0N0-II in the NC-LTG group underwent a longer operation than the LTG group, while no significant difference was found in any perioperative index for the pTNM III patients. A multivariate analysis showed that an operation time longer than 240 min was an independent risk factor (odds ratio = 3.021, 95% confidence interval: 1.160-7.868, = 0.024), while NC was not an independent risk factor for postoperative complications in LTG.

Conclusion: Despite a longer operation time and more blood loss after NC-LTG, which indicate surgical difficulty, NC-LTG exhibits acceptable short-term outcomes compared to LTG, suggesting the safety and feasibility of NC-LTG.
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http://dx.doi.org/10.4240/wjgs.v13.i5.429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167844PMC
May 2021

Dietary Sodium Restriction Results in Tissue-Specific Changes in DNA Methylation in Humans.

Hypertension 2021 Jun 14:HYPERTENSIONAHA12017351. Epub 2021 Jun 14.

Department of Physiology, Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee. (X.P., C.Y., P.L., M.L.R., Y. Li, A.M.B., Yong Liu, A.W.C., D.L.M., M.L.).

Dietary sodium affects blood pressure (BP) and vascular function. Animal studies suggest epigenetic changes (eg, DNA methylation) are involved. We hypothesized that sodium restriction induces methylation changes in T cells and arterioles in humans. Fifty subjects (49% women) were placed on 1200-mg sodium/day diet for 2 weeks. BP and brachial artery flow-mediated dilation were evaluated. Methylation sequencing (pre- and post-diet) was performed on T-cell (n=50) and biopsied arteriolar (n=10) DNA. RNA sequencing was also performed on arterioles (n=11). Over 2 weeks, mean sodium consumption was 946 mg/day. Average BP reductions after low-sodium intake were -8±13/-4±9 mm Hg (<0.001). Flow-mediated dilation improved (5.8±2.9% to 6.8±3.4%; =0.03). T-cell DNA was substantially more methylated than arterioles. The differentially methylated regions (false discovery rate, <0.05) identified in T cells and arterioles after sodium restriction were located in 117 and 71 genes, respectively. Four genes were identified in both T cells and arterioles (=0.009 for the overlap). The dietary effects on methylation in several DNA regions were associated with dietary effects on BP. Several differentially expressed genes in arterioles contained differentially methylated regions at the significance level of <0.05. In addition, 46 genes contained differentially methylated regions in both human and SS/Mcw rat T cells (=0.03 for the overlap). Sodium restriction significantly affected DNA methylation in T cells and arterioles, some of which are associated with BP. Methylation patterns and sodium effects on methylation are largely tissue specific but also have overlaps between tissues and species. These findings may lead to better understanding of dietary sodium interactions with cellular processes and, therefore, novel therapeutic targets.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.17351DOI Listing
June 2021

Multi-functional carboxymethyl chitin-based nanoparticles for modulation of tumor-associated macrophage polarity.

Carbohydr Polym 2021 Sep 24;267:118245. Epub 2021 May 24.

Key Laboratory of Coal Conversion and New Carbon Materials of Hubei Province, School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan, Hubei 430081, China; State Key Laboratory of Separation Membranes and Membrane Process, School and Chemical Engineering & School of Environmental Science and Engineering, Tiangong University, Tianjin 300378, China; College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, Hubei 430072, China. Electronic address:

Current challenge of using cytokines is its poor distribution and systemic side effects. To avoid this issue, we prepared the tumor-targeted and microenvironment-responsive nanocarriers (TRN), which were consisted of α-tocopheryl succinate (α-TOS) loaded mesoporous silica nanoparticles as cores, and surface-modified by thioketal-linkage, electrostatically coated with carboxymethyl chitin, and further anchored glucose-regulated protein 78-binding peptide as shells for encapsulating IL-12. TRN showed a size of 260 nm after encapsulated IL-12 and α-TOS with loading content of 0.0206% and 7.21%, respectively, and exhibited good biocompatibility to 4 T1 cells and macrophages. Moreover, IL-12/α-TOS loaded TRN displayed obvious anti-tumor efficacy on BALB/c nude mice bearing 4 T1 tumors, which was derived from promoted targeting to tumor tissue, endocytosed by macrophages and locally release IL-12 to subsequently repolarize tumor-associated macrophages into tumoricidal M1 phenotype with reduced side effects. The nanosystem exhibited as a promising strategy with functional conversion of macrophages in tumor microenvironment for anti-tumor therapy.
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http://dx.doi.org/10.1016/j.carbpol.2021.118245DOI Listing
September 2021

The role of circTmeff-1 in incubation of context-induced morphine craving.

Pharmacol Res 2021 Jun 8;170:105722. Epub 2021 Jun 8.

College of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, Hebei Province, Shijiazhuang 050017, PR China. Electronic address:

A progressive increase in drug craving following drug exposure is an important trigger of relapse. CircularRNAs (CircRNAs), key regulators of gene expression, play an important role in neurological diseases. However, the role of circRNAs in drug craving is unclear. In the present study, we trained mice to morphine conditioned place preference (CPP) and collected the nucleus accumbens (NAc) sections on abstinence day 1 (AD1) and day 14 (AD14) for RNA-sequencing. CircTmeff-1, which was highly expressed in the NAc core, was associated with incubation of context-induced morphine craving. The gain- and loss- of function showed that circTmeff-1 was a positive regulator of incubation. Simultaneously, the expression of miR-541-5p and miR-6934-3p were down-regulated in the NAc core during the incubation period. The dual luciferase reporter, RNA pulldown, and fluorescence insitu hybridization assays confirmed that miR-541-5p and miR-6934-3p bind to circTmeff-1 selectively. Furthermore, bioinformatics and western blot analysis suggested that vesicle-associated membrane protein 1 (VAMP1) and neurofascin (NFASC), both overlapping targets of miR-541-5p and miR-6934-3p, were highly expressed during incubation. Lastly, AAV-induced down-regulation of circTmeff-1 decreased VAMP1 and NFASC expression and incubation of morphine craving. These findings suggested that circTmeff-1, a novel circRNA, promotes incubation of context-induced morphine craving by sponging miR-541/miR-6934 in the NAc core. Thus, circTmeff-1 represents a potential therapeutic target for context-induced opioid craving, following prolonged abstinence.
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http://dx.doi.org/10.1016/j.phrs.2021.105722DOI Listing
June 2021

CircRNA NALCN acts as an miR-493-3p sponge to regulate PTEN expression and inhibit glioma progression.

Cancer Cell Int 2021 Jun 10;21(1):307. Epub 2021 Jun 10.

Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Background: An increasing number of studies have shown that circular RNAs (circRNAs) play important roles in the regulation of tumor progression. Therefore, we explored the expression characteristics, function, and related mechanism of the newly identified circNALCN in glioma.

Methods: RNA sequencing was used to analyze the expression profiles of circRNAs in brain tissue from five glioma cases and four normal controls. Quantitative real-time polymerase chain reaction was implemented to examine the levels of circNALCN, miR-493-3p, and phosphatase and tensin homolog (PTEN). Cell counting kit 8 assays were performed to analyze cell proliferation, and cell migration was assessed by the wound healing test and Transwell assay. Dual-luciferase reporter, fluorescence in situ hybridization, and RNA pulldown assays were performed to confirm the role of circNALCN as an miR-493-3p sponge, weakening the inhibitory effect of miR-493-3p on target PTEN expression.

Results: The downregulated expression of circNALCN was observed in both glioma tissues and cell lines. CircNALCN expression was negatively correlated with World Health Organization grade and overall survival in patients with glioma. Functionally, the overexpression of circNALCN significantly inhibited the proliferation and migration of glioma cells, whereas miR-493-3p mimics counteracted these effects. The mechanistic analysis demonstrated that circNALCN acted as a competing endogenous RNA for miR-493-3p to relieve the repressive effects of miR-493-3p on its target, PTEN, suppressing glioma tumorigenesis.

Conclusions: CircNALCN inhibits the progression of glioma through the miR-493-3p/PTEN axis, providing a developable biomarker and therapeutic target for glioma patients.
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http://dx.doi.org/10.1186/s12935-021-02001-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194043PMC
June 2021

The role of Mfn2 in the structure and function of ER-mitochondrial tethering in vivo.

J Cell Sci 2021 Jun 10. Epub 2021 Jun 10.

Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.

The mitochondria-ER contacts (MERCs) plays an essential role in multiple cell physiological process. While Mfn2 was the first protein implicated in the formation of MERCs, it is debated whether it acts as a tether or antagonizer, largely based on in vitro studies. To understand the role of Mfn2 in MERCs in vivo, we characterized ultrastructural and biochemical changes of MERCs in pyramidal neurons of hippocampus in Mfn2 conditional knockout (KO) mice and in Mfn2 overexpression (OE) mice and found Mfn2 ablation caused reduced close contacts while Mfn2 OE caused increased close contacts between ER and mitochondria in vivo. Functional studies on SH-SY5Y cells with Mfn2 KO or overexpression demonstrating similar biochemical changes found that mitochondrial calcium uptake along with IP3R3-Grp75 interaction was decreased in Mfn2 KO cells but increased in the Mfn2 OE cells. Lastly, we found Mfn2 KO decreased and Mfn2 OE increased the interaction between the ER-mitochondria tethering pair of VAPB-PTPIP51. In conclusion, our study supports the notion that Mfn2 plays a critical role in ER-mitochondrial tethering and the formation of close contacts in neuronal cells in vivo.
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http://dx.doi.org/10.1242/jcs.253443DOI Listing
June 2021

π-Conjugated Macrocycle Host-Guest Coassembly with C60 on HOPG.

Langmuir 2021 Jun 10;37(24):7486-7491. Epub 2021 Jun 10.

CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology (NCNST), Beijing 100190, China.

Two kinds of π-conjugated macrocycles with aggregation-induced emission (AIE) properties were investigated by scanning tunneling microscopy (STM) to elucidate their self-assembly behaviors and interaction with C60 on a highly oriented pyrolytic graphite (HOPG) surface. Both TPEMC and TPEMCS could self-assemble into orderly cavity structures. However, C60 guest molecules could only successfully enter the cavity of TPEMC to form a stable TPEMC + C60 host-guest coassembly structure. Density functional theory (DFT) calculations were also used to interpret the assembly mechanisms. This work disclosed the assembly characteristic of these new types of conjugated macrocyclic compounds, which was helpful to develop new structural porous luminescent materials.
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http://dx.doi.org/10.1021/acs.langmuir.1c00886DOI Listing
June 2021

[Analysis of 137740 dental emergency cases from 2017 to 2018].

Shanghai Kou Qiang Yi Xue 2021 Apr;30(2):151-155

Department of General Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology. Shanghai 200011, China.

Purpose: To analyze the clinical data of oral emergency cases and the characteristics of oral emergency diseases, and provide clinical basis for improving the quality of oral emergency treatment and making reasonable arrangement.

Methods: A total of 137 740 patients in oral emergency department from January 1st, 2017 to December 31st, 2018 were collected and analyzed retrospectively according to gender, age, time of visit and diagnosis. The results were analyzed with Chi-square test by Excel 7.0 and SPSS 19.0 software package.

Results: The ratio of men and women was 1.13:1, with an average age of 35.71 years. The highest incidence was seen in October 2018, and the lowest was in February 2017. The peak time of oral emergency was 20:00 to 21:00. The top three disease entity were maxillofacial injury (29.17%), facial infection (26.95%) and pulpitis (10.08%).

Conclusions: There is a wide range of diseases and a large number of patients in oral emergency and the visiting time is relatively concentrated. Dentists for emergency need to master the professional knowledge of oral surgery and endodontics. In order to make precise strategies to formulate the scale of oral emergency, considerations should be taken with the changing features of the period and month of oral emergency treatment.
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April 2021

A role for the ribosome-associated complex in activation of the IRE1 branch of UPR.

Cell Rep 2021 Jun;35(10):109217

Department of Physiology, UT Southwestern Medical Center, Dallas, TX 75390, USA; CFFT Lab, Cystic Fibrosis Foundation, Lexington, MA 02421, USA. Electronic address:

The ubiquitous ribosome-associated complex (RAC) is a chaperone that spans ribosomes, making contacts near both the polypeptide exit tunnel and the decoding center, a position prime for sensing and coordinating translation and folding. Loss of RAC is known to result in growth defects and sensitization to translational and osmotic stresses. However, the physiological substrates of RAC and the mechanism(s) by which RAC is involved in responding to specific stresses in higher eukaryotes remain obscure. The data presented here uncover an essential function of mammalian RAC in the unfolded protein response (UPR). Knockdown of RAC sensitizes mammalian cells to endoplasmic reticulum (ER) stress and selectively interferes with IRE1 branch activation. Higher-order oligomerization of the inositol-requiring enzyme 1α (IRE1α) kinase/endoribonuclease depends upon RAC. These results reveal a surveillance function for RAC in the UPR, as follows: modulating IRE1α clustering as required for endonuclease activation and splicing of the substrate Xbp1 mRNA.
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http://dx.doi.org/10.1016/j.celrep.2021.109217DOI Listing
June 2021