Publications by authors named "Hong Zhu"

1,438 Publications

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and Serve as Potential Diagnostic Biomarkers of Acute Myocardial Infarction Based on Integrated Bioinformatics Analyses.

DNA Cell Biol 2021 Jun 10. Epub 2021 Jun 10.

Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.

This study aimed to explore the potential diagnostic biomarkers and mechanisms underlying acute myocardial infarction (AMI). We downloaded four datasets (GSE19339, GSE48060, GSE66360, and GSE97320) from the Gene Expression Omnibus database and combined them as an integrated dataset. A total of 153 differentially expressed genes (DEGs) were analyzed by the linear models for microarray analysis (LIMMA) package. Weighted gene co-expression network analysis was used to screen for the significant gene modules. The intersection of DEGs and genes in the most significant module was termed "common genes" (CGs). CGs were mainly enriched in "inflammatory response," "neutrophil chemotaxis," and "IL-17 signaling pathway" through functional enrichment analyses. Subsequently, 15 genes were identified as the hub genes in the protein-protein interaction network. The Fc fragment of IgE receptor Ig () and prostaglandin-endoperoxide synthase 2 () showed significantly increased expression in AMI patients and mice at the 12-h time point in our experiments. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of and . The area under ROC curve of and was 77.6% and 80.7%, respectively. Moreover, the micro (mi)RNA-messenger (m)RNA network was also visualized; the results showed that miRNA-143, miRNA-144, and miRNA-26 could target in AMI progression.
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http://dx.doi.org/10.1089/dna.2020.6447DOI Listing
June 2021

Palladium-Catalyzed C-P(III) Bond Formation by Coupling ArBr/ArOTf with Acylphosphines.

J Org Chem 2021 Jun 11. Epub 2021 Jun 11.

State Key Laboratory of Chemical Resource Engineering, Department of Organic Chemistry, College of Chemistry, Beijing University of Chemical Technology, Beijing 100029, China.

Palladium-catalyzed C-P bond formation reaction of ArBr/ArOTf using acylphosphines as differential phosphination reagents is reported. The acylphosphines show practicable reactivity with ArBr and ArOTf as the phosphination reagents, though they are inert to the air and moisture. The reaction affords trivalent phosphines directly in good yields with a broad substrate scope and functional group tolerance. This reaction discloses the acylphosphines' capability as new phosphorus sources for the direct synthesis of trivalent phosphines.
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http://dx.doi.org/10.1021/acs.joc.1c00937DOI Listing
June 2021

Traumatic brain injury induced by exposure to blast overpressure via ear canal.

Neural Regen Res 2022 Jan;17(1):115-121

Departmant of Otolaryngology and Head Neck Surgery; Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, MS, USA.

Exposure to explosive shockwave often leads to blast-induced traumatic brain injury in military and civilian populations. Unprotected ears are most often damaged following exposure to blasts. Although there is an association between tympanic membrane perforation and TBI in blast exposure victims, little is known about how and to what extent blast energy is transmitted to the central nervous system via the external ear canal. The present study investigated whether exposure to blasts directed through the ear canal causes brain injury in Long-Evans rats. Animals were exposed to a single blast (0-30 pounds per square inch (psi)) through the ear canal, and brain injury was evaluated by histological and behavioral outcomes at multiple time-points. Blast exposure not only caused tympanic membrane perforation but also produced substantial neuropathological changes in the brain, including increased expression of c-Fos, induction of a profound chronic neuroinflammatory response, and apoptosis of neurons. The blast-induced injury was not limited only to the brainstem most proximal to the source of the blast, but also affected the forebrain including the hippocampus, amygdala and the habenula, which are all involved in cognitive functions. Indeed, the animals exhibited long-term neurological deficits, including signs of anxiety in open field tests 2 months following blast exposure, and impaired learning and memory in an 8-arm maze 12 months following blast exposure. These results suggest that the unprotected ear canal provides a locus for blast waves to cause TBI. This study was approved by the Institutional Animal Care and Use Committee at the University of Mississippi Medical Center (Animal protocol# 0932E, approval date: September 30, 2016 and 0932F, approval date: September 27, 2019).
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http://dx.doi.org/10.4103/1673-5374.314311DOI Listing
January 2022

A case of hepatic paragonimiasis was misdiagnosed as hepatocellular carcinoma with rupture and haemorrhage.

J Int Med Res 2021 Jun;49(6):3000605211012668

Department of Hepatobiliary Surgery, Kunming Medical University, The Second Affiliated Hospital of Kunming Medical College, Kunming, Yunnan Province, China.

Paragonimiasis is a disease caused by parasitic infections that mainly involve the lungs. However, it can also produce ectopic infections, such as when the parasites invade the liver, brain and subcutaneous tissue, which then cause different symptoms. This current case report describes a 55-year-old male patient with hepatic paragonimiasis that was misdiagnosed as liver cancer with rupture and haemorrhage. The initial computed tomography findings suggested ruptured liver cancer. The patient underwent laparoscopic right hemihepatectomy. Postoperative pathological analysis resulted in a diagnosis of hepatic paragonimiasis. The patient recovered well postoperatively and was treated with 25 mg/kg praziquantel orally three times a day for 3 days after discharge with good efficacy. In this present case, the rupture and haemorrhage of the liver mass made it difficult for the treating physicians to consider hepatic paragonimiasis, which lead to the initial misdiagnosis of this patient. Although paragonimiasis is very rare, medical staff should be vigilant and have a comprehensive understanding of the different diseases that can cause liver masses so that misdiagnosis can be avoided.
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http://dx.doi.org/10.1177/03000605211012668DOI Listing
June 2021

Effect of Soy Protein Isolate on Textural Properties, Cooking Properties and Flavor of Whole-Grain Flat Rice Noodles.

Foods 2021 May 14;10(5). Epub 2021 May 14.

School of Chemistry and Food Engineering, Changsha University of Science and Technology, Changsha 410114, China.

To investigate the effect of soy protein isolate on the quality of whole-grain flat rice noodles, the texture as well as the cooking properties and flavor of flat rice noodles, whole-grain flat rice noodles and whole-grain flat rice noodles with soy protein isolate were investigated. Among the three tested rice noodles, whole-grain flat rice noodles with soy protein isolate showed the highest cohesiveness, adhesiveness, resilience, and springiness. Compared to the flat rice noodles and whole-grain flat rice noodles, whole-grain flat rice noodles with soy protein isolate increased their moisture content and water absorption, whereas the opposite trend was observed for their cooking loss. The electronic nose analysis showed stronger response values at W5S, W1W, and W2W. Solid phase micro extraction and gas chromatography-mass spectrometry results showed that aldehydes are the main volatile compounds in whole-grain flat rice noodles and whole-grain flat rice noodles with soy protein isolate. Moreover, seven more volatile compounds were detected in whole-grain flat rice noodles with soy protein isolate compared to flat rice noodles and whole-grain flat rice noodles. The whole-grain flat noodles with the addition of SPI are more sensory acceptable. Thus, soy protein isolate, as a natural and safe additive, could be used to improve the quality and enrich the flavor of whole-grain flat rice noodles.
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http://dx.doi.org/10.3390/foods10051085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153555PMC
May 2021

Discovery of 5,6-Bis(4-methoxy-3-methylphenyl)pyridin-2-amine as a WSB1 Degrader to Inhibit Cancer Cell Metastasis.

J Med Chem 2021 Jun 1. Epub 2021 Jun 1.

Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, P. R. China.

The gain of cell motility is an essential prerequisite for cancer metastasis. The ubiquitin ligase subunit WD repeat and SOCS box-containing 1 (WSB1) has been demonstrated to regulate hypoxia-driven tumor cell migration. However, there is still a lack of methods for discovering inhibitors targeting the WSB1 axis. Here, we employed phenotypic screening models and identified compound that displayed migration inhibitory activity against WSB1-overexpressing cells. Further studies indicated that it may function as a WSB1 degrader, thus leading to the accumulation of the Rho guanosine diphosphate dissociation inhibitor 2 (RhoGDI2) protein, reversing the expression of downstream F-actin and formation of membrane ruffles, and disturbing the migration capacity of cancer cells. Moreover, compound exhibited a promising anticancer metastatic effects. Our findings show the discovery of a new WSB1 degrader, providing a unique solution for the treatment of cancer metastasis.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00586DOI Listing
June 2021

Disrupted Resting-State Functional Connectivity between the Dorsal Attention, Default Mode, and Frontoparietal Networks in Nonorganic Gastrointestinal Disorder Patients with Spleen Deficiency Syndrome.

Evid Based Complement Alternat Med 2021 7;2021:6681903. Epub 2021 May 7.

The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.

Introduction: Spleen deficiency syndrome (SDS), a common clinical syndrome of traditional Chinese medicine, is manifested with digestive symptoms and cognitive impairments. However, the cognitive neural mechanism in brain networks of SDS still remained unclear. Our aim was to investigate the changes between the default mode, dorsal attention, and frontoparietal networks in SDS.

Methods: Twenty nonorganic gastrointestinal disorder (NOGD) patients with SDS and eighteen healthy controls were enrolled to attend functional magnetic resonance imaging scan and participated a continuous performance test (CPT) before scanning.

Results: Compared with healthy controls, NOGD patients with SDS showed the significantly increased functional connectivity (FC) between dorsal attention network (DAN) and left frontal-parietal control network (LFPN) and significantly decreased FC between LFPN and default mode network (DMN). The functional network connectivity analysis showed positive correlation coefficients between the DAN and LFPN and DAN and DMN as well as negative correlation between LFPN and DMN in NOGD patients with SDS compared with healthy controls. Correlation analysis revealed that the increased FC between LFPN and DAN was positively correlated with 4-digitnumber reaction time mean (RTM) and 3-digitnumber RTM.

Conclusion: Our study may provide novel insights into the relationship among the DMN, DAN, and FPN in NOGD patients with SDS to deepen our understanding of the neuropsychological mechanisms of SDS.
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http://dx.doi.org/10.1155/2021/6681903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123991PMC
May 2021

The design of high performance photoanode of CQDs/TiO/WO based on DFT alignment of lattice parameter and energy band, and charge distribution.

J Colloid Interface Sci 2021 May 18;600:828-837. Epub 2021 May 18.

School of Environmental Science and Engineering, Key Laboratory of Thin Film and Microfabrication Technology (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, PR China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, PR China. Electronic address:

Photoanode is the key issue for photoelectrocatalytic (PEC) water splitting and organics degradation. However, it always faces several restrictions including severe photocorrosion, low charge separation and transfer efficiencies, poor visible light harvesting, and sluggish interfacial reaction kinetics, which often required a variety of modifications with only low improvements achieved. Herein, a high performance CQDs/TiO/WO photoanode was designed on the basis of density function theory (DFT) alignment of lattice parameters and energy band, and charge distribution. The TiO/WO heterojunction can abate photocorrosion through the hetero-epitaxial growth of TiO (001) on WO (002) for the lattice mismatch <3% eliminating dangling bonds, with high corrosion resistance and photostability of TiO. As the built-in field constructed by a staggered band alignment structure with the valence band offset (VBO) of 0.51 eV, the photogenerated carriers transfer and separation are promoted dramatically. Through the DFT calculations, the sunlight absorption wavelength can be extended, and the interfacial reaction kinetics can be expedited with the modification of carbon quantum dots (CQDs) on TiO/WO, due to the narrower bandgap (E) and the accumulation of electrons at TiO side. The DFT designed CQDs/TiO/WO photoanode significantly increase photocurrent density from 0.90 to 2.03 mA cm at 1.23 V, charge separation efficiency from 56.3 to 79.2% and charge injection efficiency from 51.2 to 70.4%, and extend light absorption edge from 455 to 463 nm over pristine WO, with better photostability and lower holes-to-water resistance.
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http://dx.doi.org/10.1016/j.jcis.2021.05.086DOI Listing
May 2021

Self-powered locomotion of a hydrogel water strider.

Sci Robot 2021 Apr;6(53)

Department of Materials Science, State Key Laboratory of ASIC and Systems, Fudan University, 200433 Shanghai, P. R. China.

Hydrogels are an exciting class of materials for new and emerging robotics. For example, actuators based on hydrogels have impressive deformability and responsiveness. Studies into hydrogels with autonomous locomotive abilities, however, are limited. Existing hydrogels achieve locomotion through the application of cyclical stimuli or chemical modifications. Here, we report the fabrication of active hydrogels with an intrinsic ability to move on the surface of water without operated stimuli for up to 3.5 hours. The active hydrogels were composed of hydrophobic and hydrophilic groups and underwent a dynamic wetting process to achieve spatial and temporal control of surface tension asymmetry. Using surface tension, the homogeneous active hydrogels propelled themselves and showed controlled locomotion on water, similar to common water striders.
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http://dx.doi.org/10.1126/scirobotics.abe7925DOI Listing
April 2021

Biomarkers for hepatocellular carcinoma based on body fluids and feces.

World J Gastrointest Oncol 2021 May;13(5):351-365

Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital (Navy Medical University), Second Military Medical University, Shanghai 200438, China.

Novel non-/minimally-invasive and effective approaches are urgently needed to supplement and improve current strategies for diagnosis and management of hepatocellular carcinoma (HCC). Overwhelming evidence from published studies on HCC has documented that multiple molecular biomarkers detected in body fluids and feces can be utilized in early-diagnosis, predicting responses to specific therapies, evaluating prognosis before or after therapy, as well as serving as novel therapeutic targets. Detection and analysis of proteins, metabolites, circulating nucleic acids, circulating tumor cells, and extracellular vesicles in body fluids (, blood and urine) and gut microbiota (, in feces) have excellent capabilities to improve different aspects of management of HCC. Numerous studies have been devoted in identifying more promising candidate biomarkers and therapeutic targets for diagnosis, treatment, and monitoring responses of HCC to conventional therapies, most of which may improve diagnosis and management of HCC in the future. This review aimed to summarize recent advances in utilizing these biomarkers in HCC and discuss their clinical significance.
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http://dx.doi.org/10.4251/wjgo.v13.i5.351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131906PMC
May 2021

miR-183-5p Is a Potential Molecular Marker of Systemic Lupus Erythematosus.

J Immunol Res 2021 6;2021:5547635. Epub 2021 May 6.

Department of Medical Genetics and Cell Biology, College of Basic Medicine, Ningxia Medical University, Yinchuan, Ningxia, China.

Objective: To investigate microRNA (miRNA) expression profiles in individuals with systemic lupus erythematosus (SLE) and identify the valuable miRNA biomarkers in diagnosing and monitoring SLE.

Methods: Next-generation sequencing (NGS) was performed to assess miRNA amounts in peripheral blood mononuclear cells (PBMCs) from four SLE cases and four healthy controls. Quantitative polymerase chain reaction (qPCR) was carried out for validating candidate miRNAs in 32 SLE cases and 32 healthy controls. In addition, receiver operating characteristic (ROC) curve analysis was completed to evaluate diagnostic performance. Finally, the associations of candidate miRNAs with various characteristics of SLE were analyzed.

Results: A total of 157 miRNAs were upregulated, and 110 miRNAs were downregulated in PBMCs from SLE cases in comparison to healthy controls, of which the increase of miR-183-5p and decrease of miR-374b-3p were validated by qPCR and both showed good diagnostic performance for SLE diagnosis. Besides, miR-183-5p expression levels displayed a positive association with SLE disease activity index (SLEDAI) and anti-dsDNA antibody amounts.

Conclusion: Our data indicated that miR-183-5p is a promising biomarker of SLE.
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http://dx.doi.org/10.1155/2021/5547635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124875PMC
May 2021

Adiposity Measurements and Metabolic Syndrome Are Linked Through Circulating Neuregulin 4 and Adipsin Levels in Obese Adults.

Front Physiol 2021 4;12:667330. Epub 2021 May 4.

Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Background: Adiposity and adipokines are associated with metabolic disorders, but little is known regarding that whether adiposity measurements link metabolic syndrome (MetS) through circulating neuregulin 4 (Nrg4) and adipsin levels.

Materials And Methods: A total of 1212 subjects with a waist circumference greater than 90 cm for men or 80 cm for women were enrolled from a Chinese community. Circulating Nrg4 and adipsin levels were measured using commercial kits. Mediation analyses of circulating Nrg4 and adipsin were performed in the study using linear and logistic regression.

Results: Subjects with MetS had higher waist circumference, visceral fat level, and circulating adipsin level, and lower levels of circulating Nrg4 and muscle mass to visceral fat (MVF) ratio (all < 0.05). In multivariable logistic regression analyses, after adjusting for confounding variables, per standard deviation (SD) increase in waist circumference and visceral fat level were significantly associated with increased odds of MetS [OR (95% CI), 1.42 (1.22-1.64); 2.20 (1.62-2.99); respectively]; and per SD reduction in MVF ratio was significantly associated with reduced odds of MetS [OR (95% CI), 0.65 (0.55-0.77)]. In the mediation analyses, both circulating Nrg4 and adipsin levels mediated the association between waist circumference (8.31% and 18.35%, respectively), visceral fat level (7.50% and 9.98%, respectively), and MVF ratio (5.80% and 9.86%, respectively) and MetS after adjustments.

Conclusion: These findings indicate that adiposity measurements and MetS are linked through circulating Nrg4 and adipsin levels in obese adults, suggesting that circulating Nrg4 and adipsin levels might be potential predictors for management of MetS.
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http://dx.doi.org/10.3389/fphys.2021.667330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129583PMC
May 2021

AKR1C1 connects autophagy and oxidative stress by interacting with SQSTM1 in a catalytic-independent manner.

Acta Pharmacol Sin 2021 May 20. Epub 2021 May 20.

Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

Targeting autophagy might be a promising anticancer strategy; however, the dual roles of autophagy in cancer development and malignancy remain unclear. NSCLC (non-small cell lung cancer) cells harbour high levels of SQSTM1 (sequestosome 1), the autophagy receptor that is critical for the dual roles of autophagy. Therefore, mechanistic insights into SQSTM1 modulation may point towards better approaches to treat NSCLC. Herein, we used multiple autophagy flux models and autophagy readouts to show that aldo-keto reductase family 1 member C1 (AKR1C1), which is highly expressed in NSCLC, promotes autophagy by directly binding to SQSTM1 in a catalytic-independent manner. This interaction may be strengthened by reactive oxygen species (ROS), important autophagy inducers. Further mechanistic research demonstrated that AKR1C1 interacts with SQSTM1 to augment SQSTM1 oligomerization, contributing to the SQSTM1 affinity for binding cargo. Collectively, our data reveal a catalytic-independent role of AKR1C1 for interacting with SQSTM1 and promoting autophagy. All these findings not only reveal a novel functional role of AKR1C1 in the autophagy process but also indicate that modulation of the AKR1C1-SQSTM1 interaction may be a new strategy for targeting autophagy.
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http://dx.doi.org/10.1038/s41401-021-00673-wDOI Listing
May 2021

Dynamics of neutralizing antibody responses to SARS-CoV-2 in patients with COVID-19: an observational study.

Signal Transduct Target Ther 2021 05 18;6(1):197. Epub 2021 May 18.

State Key Laboratory of Organ Failure Research, National Clinical Research Center for Kidney Disease, Guangdong Provincial Clinical Research Center for Kidney Disease, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Our understanding of the protective immunity, particularly the long-term dynamics of neutralizing antibody (NAbs) response to SARS-CoV-2, is currently limited. We enrolled a cohort of 545 COVID-19 patients from Hubei, China, who were followed up up to 7 months, and determined the dynamics of NAbs to SARS-CoV-2 by using a surrogate virus neutralization test (sVNT). In our validation study, sVNT IC titers and the neutralization rate measured at a single dilution (1:20) were well correlated with FRNT titers (r = 0.85 and 0.84, respectively). The median time to seroconversion of NAbs was 5.5 days post onset of symptoms. The rate of positive sVNT was 52% in the first week, reached 100% in the third week, and remained above 97% till 6 months post onset. Quantitatively, NAbs peaked in the fourth week and only a quarter of patients had an estimated peak titer of >1000. NAbs declined with a half-time of 61 days (95% CI: 49-80 days) within the first two months, and the decay deaccelerated to a half-time of 104 days (95% CI: 86-130 days) afterward. The peak levels of NAbs were positively associated with severity of COVID-19 and age, while negatively associated with serum albumin levels. The observation that the low-moderate peak neutralizing activity and fast decay of NAbs in most naturally infected individuals called for caution in evaluating the feasibility of antibody-based therapy and vaccine durability. NAbs response positively correlated with disease severity, warning for the possibility of repeat infection in patients with mild COVID-19.
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http://dx.doi.org/10.1038/s41392-021-00611-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129700PMC
May 2021

Rice (Oryza sativa L.) recruits sphingomonas strain HJY-rfp via root exudate regulation to increase chlorpyrifos stress tolerance and boost residual catabolism.

J Exp Bot 2021 May 14. Epub 2021 May 14.

Institute of Agricultural Resources and Environment, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China.

Inoculation with pollution-degrading endophytes boosts the catabolism of residual contamination and promotes the pollution adaptation of host plants. We investigated the interaction pattern between Sphingomonas strain HJY-rfp, a chlorpyrifos (CP)-degrading endophytic bacterium, and rice under pesticide stress using hydroponic cultivation. We observed a notable trend of endophytic root colonisation of rice that was treated with 10 mg L -1 CP solution, and the migration of HJY-rfp enhanced the 24 h CP degradation rate in leaves and stems by 53.36% and 40.81%, respectively. Critically, the rice root exudate profile (organic acids and amino acids) changed under CP stress, and variations in the contents of several components affected the chemotactic behaviour of HJY-rfp. HJY-rfp colonisation dramatically activated defensive enzymes, which enabled efficient scavenging of reactive oxygen species (ROS), and led to 9.71%, 22.5% and 41.87% increases in shoot length, fresh weight and accumulation of total chlorophyll, respectively, in rice suffering from oxidative damage by CP. Endophytic colonisation caused upregulation of detoxification genes that have shown a positive correlation with CP degradation in vivo (p < 0.001). Collectively, our results demonstrate that agrochemical stress causes plants to actively recruit specific symbiotic microbes to detoxify contaminants and survive better under polluted conditions.
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http://dx.doi.org/10.1093/jxb/erab210DOI Listing
May 2021

Use of repurposed and adjuvant drugs in hospital patients with covid-19: multinational network cohort study.

BMJ 2021 05 11;373:n1038. Epub 2021 May 11.

Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, South Korea.

Objective: To investigate the use of repurposed and adjuvant drugs in patients admitted to hospital with covid-19 across three continents.

Design: Multinational network cohort study.

Setting: Hospital electronic health records from the United States, Spain, and China, and nationwide claims data from South Korea.

Participants: 303 264 patients admitted to hospital with covid-19 from January 2020 to December 2020.

Main Outcome Measures: Prescriptions or dispensations of any drug on or 30 days after the date of hospital admission for covid-19.

Results: Of the 303 264 patients included, 290 131 were from the US, 7599 from South Korea, 5230 from Spain, and 304 from China. 3455 drugs were identified. Common repurposed drugs were hydroxychloroquine (used in from <5 (<2%) patients in China to 2165 (85.1%) in Spain), azithromycin (from 15 (4.9%) in China to 1473 (57.9%) in Spain), combined lopinavir and ritonavir (from 156 (<2%) in the VA-OMOP US to 2,652 (34.9%) in South Korea and 1285 (50.5%) in Spain), and umifenovir (0% in the US, South Korea, and Spain and 238 (78.3%) in China). Use of adjunctive drugs varied greatly, with the five most used treatments being enoxaparin, fluoroquinolones, ceftriaxone, vitamin D, and corticosteroids. Hydroxychloroquine use increased rapidly from March to April 2020 but declined steeply in May to June and remained low for the rest of the year. The use of dexamethasone and corticosteroids increased steadily during 2020.

Conclusions: Multiple drugs were used in the first few months of the covid-19 pandemic, with substantial geographical and temporal variation. Hydroxychloroquine, azithromycin, lopinavir-ritonavir, and umifenovir (in China only) were the most prescribed repurposed drugs. Antithrombotics, antibiotics, H2 receptor antagonists, and corticosteroids were often used as adjunctive treatments. Research is needed on the comparative risk and benefit of these treatments in the management of covid-19.
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http://dx.doi.org/10.1136/bmj.n1038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111167PMC
May 2021

Accessing Targeted Therapies: A Potential Roadblock to Implementing Precision Oncology?

JCO Oncol Pract 2021 May 10:OP2000927. Epub 2021 May 10.

Division on Hematology and Oncology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX.

Purpose: Advances in genomic techniques have led to increased use of next-generation sequencing (NGS). We evaluated the extent to which these tests guide treatment decisions.

Methods: We developed and distributed a survey assessing NGS use and outcomes to a survey pool of ASCO members. Comparisons between groups were performed with Wilcoxon two-sample, chi-square, and Fisher's exact tests.

Results: Among 178 respondents, 62% were male, 54% White, and 67% affiliated with academic centers. More than half (56%) indicated that NGS provided actionable information to a moderate or great extent. Use was highest (median ≥ 70% of cases) for lung and gastric cancer, and lowest (median < 25% of cases) in head and neck and genitourinary cancers. Approximately one third of respondents reported that, despite identification of an actionable molecular variant, patients were sometimes or often unable to access the relevant US Food and Drug Administration-approved therapy. When NGS did not provide actionable results, individuals reporting great or moderate guidance overall from NGS in treatment recommendations were more likely to request the compassionate use of an unapproved drug ( < .001), enroll on a clinical trial ( < .01), or treat off-label with a drug approved for another indication ( = .02).

Conclusion: When NGS identifies an actionable result, a substantial proportion of clinicians reported encountering challenges obtaining approved therapies on the basis of these results. Perceived overall impact of NGS appears associated with clinical behavior unrelated to actionable NGS test results, including pursuing off-label or compassionate use of unapproved therapies or referring to a clinical trial.
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http://dx.doi.org/10.1200/OP.20.00927DOI Listing
May 2021

The Influence of Val66Met Polymorphism in Brain-Derived Neurotrophic Factor on Stroke Recovery Outcome: A Systematic Review and Meta-analysis.

Neurorehabil Neural Repair 2021 Jun 6;35(6):550-560. Epub 2021 May 6.

Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China.

. A single nucleotide polymorphism at nucleotide 196 (G/A) in the human brain-derived neurotrophic factor () gene produces an amino acid substitution (valine to methionine) at codon 66(Val66Met). It is unclear whether carriers of this substitution may have worse functional outcomes after stroke. We aimed to explore the distribution of Val66Met polymorphism and evaluate the effect of different genotypes on stroke functional recovery. . Several databases were searched using the keywords or , , , , or , and . A total of 25 articles were relevant to estimate the distribution of alleles; 5 reports were applied in the meta-analysis to assess genetic differences on recovery outcomes. The genetic model analysis showed that the recessive model should be used; we combined data for AA versus GA+GG (GG-Val/Val, GA-Val/Met, AA-Met/Met). The results showed that stroke patients with AA might have worse recovery outcomes than those with GA+GG (odds ratio = 1.90; 95% CI: 1.17-3.10; = .010; = 69.2%). Overall, the A allele may be more common in Asian patients (48.6%; 95% CI: 45.8%-51.4%, = 54.2%) than Caucasian patients (29.8%; 95% CI: 7.5%-52.1%; = 99.1%). However, in Caucasian patients, the frequency of the A allele in Iranians (87.9%; 95% CI: 83.4%-92.3%) was quite higher than that in other Caucasians (18.7%; 95% CI: 16.6%-20.9%; = 0.00%). . Val66Met AA carriers may have worse rehabilitation outcomes than GA+GG carriers. Further studies are needed to determine the effect of Val66Met polymorphism on stroke recovery and to evaluate this relationship with ethnicity, sex, age, stroke type, observe duration, stroke severity, injury location, and therapies.
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http://dx.doi.org/10.1177/15459683211014119DOI Listing
June 2021

Heterogeneous [email protected]@NF nanosheet arrays directly used as high efficiency bifunctional electrocatalyst for water decomposition.

J Colloid Interface Sci 2021 Oct 20;599:300-312. Epub 2021 Apr 20.

Key Laboratory of Eco-Environment-Related Polymer Materials of Ministry of Education, Key Laboratory of Polymer Materials of Gansu Province, College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou, Gansu 730070, PR China. Electronic address:

Developing and designing bifunctional electrocatalysts are very important for the production of hydrogen from water electrolysis. The reasonable interface modulation can effectively lead to the optimization of electronic configuration through the interface electron transfer in the heterostructures and thus resulting in the enhanced efficiency. In this work, self-supported and heterogeneous interface-rich [email protected]@NF electrocatalyst for overall water splitting was designed and prepared through a controllable step-wise hydrothermal process. Density functional theory calculations suggest that heterogeneous interface formed between NiS and FeNiS can optimize the Gibbs free energy for H* adsorption (ΔG). Benefiting from the open structure of the nanosheet arrays, the abundant heterogeneous interfaces in [email protected]@NF composite, the positive synergistic effect between NiS and FeNiS, and the good conductivity of foamed nickel (NF) substrate, the optimized [email protected]@NF nanoarray catalyst displayed excellent electrocatalytic activities, the overpotential is only 83 mV and 235 mV for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) at 10 mA cm, respectively. Importantly, an alkaline electrolyser directly using the [email protected]@NF as both the anode and cathode achieved an ultralow cell voltage of 1.46 V, accompanied by outstanding stability. The performance is better than that of most other transition-metal sulfides electrocatalysts. This work may provide a useful strategy for reasonably regulating heterogeneous interfaces to effectively improve the performance of materials, thus accelerating the practical application of transition-metal sulfides electrocatalysts for overall water splitting.
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http://dx.doi.org/10.1016/j.jcis.2021.04.004DOI Listing
October 2021

Gestational high-fat diet impaired demethylation of Pparα and induced obesity of offspring.

J Cell Mol Med 2021 Jun 6;25(12):5404-5416. Epub 2021 May 6.

The Key Laboratory of Reproductive Genetics (Zhejiang University School of Medicine), Ministry of Education, Hangzhou, China.

Gestational and postpartum high-fat diets (HFDs) have been implicated as causes of obesity in offspring in later life. The present study aimed to investigate the effects of gestational and/or postpartum HFD on obesity in offspring. We established a mouse model of HFD exposure that included gestation, lactation and post-weaning periods. We found that gestation was the most sensitive period, as the administration of a HFD impaired lipid metabolism, especially fatty acid oxidation in both foetal and adult mice, and caused obesity in offspring. Mechanistically, the DNA hypermethylation level of the nuclear receptor, peroxisome proliferator-activated receptor-α (Pparα), and the decreased mRNA levels of ten-eleven translocation 1 (Tet1) and/or ten-eleven translocation 2 (Tet2) were detected in the livers of foetal and adult offspring from mothers given a HFD during gestation, which was also associated with low Pparα expression in hepatic cells. We speculated that the hypermethylation of Pparα resulted from the decreased Tet1/2 expression in mothers given a HFD during gestation, thereby causing lipid metabolism disorders and obesity. In conclusion, this study demonstrates that a HFD during gestation exerts long-term effects on the health of offspring via the DNA demethylation of Pparα, thereby highlighting the importance of the gestational period in regulating epigenetic mechanisms involved in metabolism.
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http://dx.doi.org/10.1111/jcmm.16551DOI Listing
June 2021

C-peptide ameliorates high glucose-induced podocyte dysfunction through the regulation of the Notch and TGF-β signaling pathways.

Peptides 2021 Apr 24;142:170557. Epub 2021 Apr 24.

Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China. Electronic address:

The podocyte is one of the main components of the glomerular filtration barrier in the kidney, and its injury may contribute to proteinuria, glomerulosclerosis and eventually kidney failure. C-peptide, a cleavage product of proinsulin, shows therapeutic potential for treating diabetic nephropathy (DN). The aim of this study was to investigate the effect of C-peptide on high glucose-induced podocyte dysfunction. In the present study, we found that the protective effects of islet transplantation were superior to simple insulin therapy for the treatment of DN in streptozotocin (STZ)-treated rats. And such superiority may due to the function of C-peptide secreted at the implanted site. Based on this background, we determined that the application of C-peptide significantly prevented high glucose-induced podocyte injury by increasing the expression of nephrin and synaptopodin. Meanwhile, C-peptide suppressed high glucose-induced epithelial-mesenchymal transition (EMT) and renal fibrosis via decreasing the expression of snail, vimentin, α-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF). Moreover, the Notch and transforming growth factor-β (TGF-β) signaling pathways were activated by high glucose, and treatment with C-peptide down-regulated the expression of the Notch signaling molecules Notch 1 and Jagged 1 and the TGF-β signaling molecule TGF-β1. These findings suggested that C-peptide might serve as a novel treatment method for DN and podocyte dysfunction.
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http://dx.doi.org/10.1016/j.peptides.2021.170557DOI Listing
April 2021

Early diagnosis and therapeutic strategies for hepatocellular carcinoma: From bench to bedside.

World J Gastrointest Oncol 2021 Apr;13(4):197-215

Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital (Navy Medical University), Second Military Medical University, Shanghai 200438, China.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide. The prognosis of patients with HCC remains poor largely due to the late diagnosis and lack of effective treatments. Despite being widely used, alpha-fetoprotein serology and ultrasonography have limited diagnostic performance for early-stage HCC. The emergence of omics strategies has contributed to significant advances in the development of non-invasive biomarkers for the early diagnosis of HCC including proteins, metabolites, circulating tumor deoxyribonucleic acid, and circulating non-coding ribonucleic acid. Early diagnosis is beneficial to patients as it increases the proportion who can be treated with curative treatment, thus prolonging survival outcomes. Currently, multiple clinical trials involving locoregional, systemic therapies, and combinations of these modalities are changing therapeutic strategies for different stage HCC. Success in several preclinical trials that involve immunotherapeutic innovations has created the potential to complement and enforce other treatment strategies in the future. This review summarizes the most recent advances in non-invasive early molecular detection, current therapy strategies, and potential immunotherapeutic innovations of HCC.
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http://dx.doi.org/10.4251/wjgo.v13.i4.197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040062PMC
April 2021

Anesthetic Complications Associated with SARS-CoV-2 in Pediatric Patients.

Anesth Analg 2021 Apr 21. Epub 2021 Apr 21.

Department of Anesthesiology and Pain Management, Division of Pediatric Anesthesia, University of Texas Southwestern, Dallas, TX and Children's Health, Dallas, TX.

Background: Coronavirus disease 19 (COVID-19) is associated with high perioperative morbidity and mortality among adults. The incidence and severity of anesthetic complications in children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We hypothesized that there would be an increased incidence of intra- and postoperative complications in children with SARS-CoV-2 infection as compared to those with negative testing.

Methods: We conducted a retrospective cohort study analyzing complications for children under 18 years of age who underwent anesthesia between April 28 and September 30, 2020 at a large, academic pediatric hospital. Each child with a positive SARS-CoV-2 test within the prior 10 days was matched to a patient with a negative SARS-CoV-2 test based on American Society of Anesthesiologists (ASA) classification, age, gender, and procedure. Children who were intubated prior to the procedure, underwent organ transplant surgery, or had severe COVID-19 were excluded. The primary outcome was the risk difference of a composite of intra- or postoperative respiratory complications in children positive for SARS-CoV-2 compared to those with negative testing. Secondarily, we used logistic regression to determine the odds ratio for respiratory complications before and after adjustment using propensity scores weighting to adjust for possible confounders. Other secondary outcomes included neurologic, cardiovascular, hematologic, and renal complications, unanticipated postoperative admission to the intensive care unit, length of hospital stay, and mortality.

Results: During the study period, 9,812 general anesthetics that had a preoperative SARS-CoV-2 test were identified. Sixty encounters occurred in patients who had positive SARS-CoV-2 testing preoperatively and 51 were included for analysis. The matched controls cohort included 99 encounters. A positive SARS-CoV-2 test was associated with a higher incidence of respiratory complications (11.8% vs 1.0%; risk difference 10.8%, 95% CI 1.6-19.8%; P = 0.003). After adjustment, the odds ratio for respiratory complications was 14.37 (95% CI 1.59-130.39; P = 0.02) for SARS-CoV-2 positive children as compared to controls. There was no occurrence of acute respiratory distress syndrome, postoperative pneumonia, or perioperative mortality in either group.

Conclusions: Pediatric patients with non-severe SARS-CoV-2 infection had higher rates of perianesthetic respiratory complications than matched controls with negative testing. However, severe morbidity was rare and there were no mortalities. The incidence of complications was similar to previously published rates of perianesthetic complications in the setting of an upper respiratory tract infection. This risk persisted after adjustment for preoperative upper respiratory symptoms, suggesting an increased risk in symptomatic or asymptomatic SARS-CoV-2 infection.
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http://dx.doi.org/10.1213/ANE.0000000000005606DOI Listing
April 2021

Neuroprotection of Heme Oxygenase-2 in Mice AfterIntracerebral Hemorrhage.

J Neuropathol Exp Neurol 2021 Apr;80(5):457-466

Department of Pathology, First Clinical Hospital, Harbin Medical University, Harbin, China.

There are few effective preventive or therapeutic strategies to mitigate the effects of catastrophic intracerebral hemorrhage (ICH) in humans. Heme oxygenase is the rate-limiting enzyme in heme metabolism; heme oxygenase-2 (HO-2) is a constitutively expressed heme oxygenase. We explored the involvement of HO-2 in a collagenase-induced mouse model of ICH in C57BL/6 wild-type and HO-2 knockout mice. We assessed oxidative stress injury, blood-brain barrier permeability, neuronal damage, late-stage angiogenesis, and hematoma clearance using immunofluorescence, Western blot, MRI, and special staining methods. Our results show that HO-2 reduces brain injury volume and brain edema, alleviates cytotoxic injury, affects vascular function in the early stage of ICH, and improves hematoma absorbance and angiogenesis in the late stage of ICH in this model. Thus, we found that HO-2 has a protective effect on brain injury after ICH.
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http://dx.doi.org/10.1093/jnen/nlab025DOI Listing
April 2021

Has the increase in the regional nodes evaluated improved survival rates for patients with locoregional colon cancer?

J Cancer 2021 5;12(9):2513-2525. Epub 2021 Mar 5.

Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China.

The guidelines for colon cancer surgery have been evolving over the past three decades. The advances in colectomy have focused mainly on the number of regional nodes evaluated (RNE). Data in this retrospective analysis were extracted from the Surveillance, Epidemiology, and End Results (SEER) linked database. Rapid growth of RNE (the median rising from 10 (6-16) to 17 (13-23)) occurred from 2000 to 2009. The rate of colon cancer patients with positive lymph nodes following colectomy was greatly decreasing only in the group with RNE greater than 12 after 2000. Patients with T4 and/or N+ cannot obtain survival benefit from the increasing trend of RNE. The apparent survival benefit for T1-3N0 patients may result from augmented false negatives in patients from previous periods. The golden period of surgical development in colon cancer, using RNE as an alternative indicator, occurred in the first decade of the 21st century. Although a more extensive lymph node evaluation is able to reduce the risk of underestimated staging, the increase of RNE does not provide survival benefits for locoregional colon cancer. A proper reduction in the scope of lymph node dissection may be reasonable in radical surgery for colon cancer.
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http://dx.doi.org/10.7150/jca.52352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040710PMC
March 2021

Mycobacterial fatty acid catabolism is repressed by FdmR to sustain lipogenesis and virulence.

Proc Natl Acad Sci U S A 2021 Apr;118(16)

CAS Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences (CAS), Shanghai 200032, China;

Host-derived fatty acids are an important carbon source for pathogenic mycobacteria during infection. How mycobacterial cells regulate the catabolism of fatty acids to serve the pathogenicity, however, remains unknown. Here, we identified a TetR-family transcriptional factor, FdmR, as the key regulator of fatty acid catabolism in the pathogen by combining use of transcriptomics, chromatin immunoprecipitation followed by sequencing, dynamic C-based flux analysis, metabolomics, and lipidomics. An mutant deficient in FdmR was severely attenuated in zebrafish larvae and adult zebrafish. The mutant showed defective growth but high substrate consumption on fatty acids. FdmR was identified as a long-chain acyl-coenzyme A (acyl-CoA)-responsive repressor of genes involved in fatty acid degradation and modification. We demonstrated that FdmR functions as a valve to direct the flux of exogenously derived fatty acids away from β-oxidation toward lipid biosynthesis, thereby avoiding the overactive catabolism and accumulation of biologically toxic intermediates. Moreover, we found that FdmR suppresses degradation of long-chain acyl-CoAs endogenously synthesized through the type I fatty acid synthase. By modulating the supply of long-chain acyl-CoAs for lipogenesis, FdmR controls the abundance and chain length of virulence-associated lipids and mycolates and plays an important role in the impermeability of the cell envelope. These results reveal that despite the fact that host-derived fatty acids are used as an important carbon source, overactive catabolism of fatty acids is detrimental to mycobacterial cell growth and pathogenicity. This study thus presents FdmR as a potentially attractive target for chemotherapy.
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http://dx.doi.org/10.1073/pnas.2019305118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072231PMC
April 2021

Upregulation of histone acetylation reverses organic anion transporter 2 repression and enhances 5-fluorouracil sensitivity in hepatocellular carcinoma.

Biochem Pharmacol 2021 Jun 8;188:114546. Epub 2021 Apr 8.

Institute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China; Cancer Center of Zhejiang University, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Hangzhou, China. Electronic address:

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. The failure of chemotherapy in HCC patients is partly due to inadequate intracellular drug accumulation caused by abnormally expressed drug transporters. Human organic anion transporter 2 (hOAT2), a transporter mainly expressed in liver and kidney, is responsible for uptake of various antineoplastic drugs such as 5-fluorouracil (5-FU). Among 32 pairs of human HCC samples, we preliminarily found that OAT2 was suppressed in HCC tissues compared with matched tumor-adjacent tissues at both mRNA and protein levels, which resulted in 5-FU resistance in HCC. However, the epigenetic regulatory mechanisms of OAT2 downregulation have not been investigated. In this study, we first proved it was histone hypoacetylation rather than DNA hypermethylation that participated in transcriptional repression of OAT2 in two HCC cell lines (BEL-7402 and SMMC-7721). In general, there were two pathways confirmed using tissues and cells: 1) Increased histone deacetylase sirtuin 7 (SIRT7) mediated loss of histone 3 lysine 18 acetylation (H3K18ac) at the promoter of OAT2 and inhibited its transcription. 2) More histone deacetylase 7 (HDAC7) instead of lysine acetyltransferase 8 (KAT8) enrichment at the promoter of OAT2 led to low levels of histone 4 lysine 16 acetylation (H4K16ac). Further, we found that histone deacetylases inhibitor vorinostat (SAHA) could reverse histone hypoacetylation state to activate OAT2 transcription and enhance uptake of classic OAT2 substrate zidovudine. Therefore, we evaluated the effect of combining SAHA and 5-FU and the results demonstrated that SAHA could sensitize HCC cells to 5-FU. Collectively, we proposed such a combination treatment to overcome 5-FU resistance in HCC from the perspective of epigenetically restoring OAT2.
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http://dx.doi.org/10.1016/j.bcp.2021.114546DOI Listing
June 2021

Development of new therapeutic options for the treatment of uveal melanoma.

FEBS J 2021 Apr 10. Epub 2021 Apr 10.

Faculty of Medicine and Health, Sydney Pharmacy School, The University of Sydney, NSW, Australia.

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Important cytogenetic and genetic risk factors for the development of UM include chromosome 3 monosomy, mutations in the guanine nucleotide-binding proteins GNAQ/GNA11, and loss of the BRACA1-associated protein 1 (BAP 1). Most primary UMs are treated conservatively with radiotherapy, but enucleation is necessary for large tumours. Despite the effectiveness of local control, up to 50% of UM patients develop metastasis for which there are no effective therapies. Attempts to utilise the targeted therapies that have been developed for the treatment of other cancers, including a range of signal transduction pathway inhibitors, have rarely produced significant outcomes in UM. Similarly, the application of immunotherapies that are effective in cutaneous melanoma to treat UM have also been disappointing. Other approaches that have been initiated involve proteasomal inhibitors and histone deacetylase inhibitors which are approved for the treatment of other cancers. Nevertheless, there have been occasional positive outcomes from these treatments in UM. Moreover, combination approaches in UM have also yielded some positive developments. It would be valuable to identify how to apply such therapies efficiently in UM, potentially via individualised tumour profiling. It would also be important to characterise UM tumours to differentiate the potential drivers of progression from those in other types of cancers. The recent identification of novel kinases and metastatic genes in UM tumours makes the development of new UM-specific treatments feasible.
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http://dx.doi.org/10.1111/febs.15869DOI Listing
April 2021

A [6+4]-cycloaddition adduct is the biosynthetic intermediate in streptoseomycin biosynthesis.

Nat Commun 2021 04 7;12(1):2092. Epub 2021 Apr 7.

State Key Laboratory of Pharmaceutical Biotechnology, Institute of Functional Biomolecules, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Life Sciences, Nanjing University, Nanjing, China.

Streptoseomycin (STM, 1) is a bacterial macrolactone that has a unique 5/14/10/6/6-pentacyclic ring with an ether bridge. We have previously identified the biosynthetic gene cluster for 1 and characterized StmD as [6 + 4]- and [4 + 2]-bispericyclase that catalyze a reaction leading to both 6/10/6- and 10/6/6-tricyclic adducts (6 and 7). The remaining steps, especially how to install and stabilize the required 10/6/6-tricyclic core for downstream modifications, remain unknown. In this work, we have identified three oxidoreductases that fix the required 10/6/6-tryciclic core. A pair of flavin-dependent oxidoreductases, StmO1 and StmO2, catalyze the direct hydroxylation at [6 + 4]-adduct (6). Subsequently, a spontaneous [3,3]-Cope rearrangement and an enol-ketone tautomerization result in the formation of 10/6/6-tricyclic intermediate 12b, which can be further converted to a stable 10/6/6-tricyclic alcohol 11 through a ketoreduction by StmK. Crystal structure of the heterodimeric complex NtfO1-NtfO2, homologues of StmO1-StmO2 with equivalent function, reveals protein-protein interactions. Our results demonstrate that the [6 + 4]-adduct instead of [4 + 2]-adduct is the bona fide biosynthetic intermediate.
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http://dx.doi.org/10.1038/s41467-021-22395-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027225PMC
April 2021

Immune Check Point Inhibitors and Immune-Related Adverse Events in Small Cell Lung Cancer.

Front Oncol 2021 18;11:604227. Epub 2021 Mar 18.

Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.

Small cell lung cancer (SCLC) is a malignant solid tumor. In recent years, although immune check point inhibitors (ICIs) have achieved important advances in the treatment of SCLC, immune-related adverse events (irAEs) have occurred at the same time during the therapeutic period. Some irAEs lead to dose reduction or treatment rejection. The immune microenvironment of SCLC is complicated, therefore, understanding irAEs associated with ICIs is of great importance and necessity for the clinical management of SCLC. However, the lack of comprehensive understanding of irAEs in patients with SCLC remains remarkable. This review aims to provide an up-to-date overview of ICIs and their associated irAEs in patients with SCLC based on present clinical data.
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http://dx.doi.org/10.3389/fonc.2021.604227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016392PMC
March 2021