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1.
Brain Pathol ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33032379

RESUMO

Pediatric low-grade gliomas were shown to be characterized by an array of distinct molecular aberrations. The recent cIMPACT-4 consensus proposed pediatric low-grade gliomas of the diffuse type to be characterized by distinct molecular changes rather than distinct histological features (2). Very recently, Fukuoka et al. described a small series of pediatric oligodendroglioma-like tumors with BRAF V600E mutations (3). Interestingly, they exhibited molecular changes usually associated with adult high grade gliomas: chromosome instability, chromosome 7 gains and chromosome 10 loss, but had an indolent natural history.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33021884

RESUMO

D. segeticola is a significant plant pathogen that causes leaf spot on tea (Camellia sinensis) in Guizhou Province, China, leading to significant losses in production (Zhao et al. 2018). Although genome sequences of D. segeticola have been published (Ren et al. 2019), no data of transcriptome and microRNA of the pathogen and host during infection are available. Here, we report the high-quality transcriptome and microRNA of D. segeticola infection using the platform of Illumina Hiseq 4000 or Illumina Hiseq 2500. The number of annotated unigenes is 10894 and 33932 at several databases for mycelia and tea. PC-3p-9306445_2, nta-MIR6149a-p3_2ss13GA18CG, mdm-MIR535a-p3_2ss13GA18CG, cst-MIR11334-p3_2ss13GA18CG, et al can target more gene, with the number of the target genes being 31, 21, 16 and 11. The sequence of transcriptome and microRNA of D. segeticola will provide an important resource for researchers studying pathogenic mechanism and disease resistance.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33053709

RESUMO

Electronic products are being updated and replaced much faster and there is therefore an increasing growth in electronic waste (e-waste). In order to promote professional recycling of e-waste, the relevant government departments of China have published a series of policies. This paper aims to unearth the evolution tendency of the networked policies towards holistic governance of China's e-waste recycling. Content analysis, quantitative text analysis and network analysis are applied to analyze relevant policy documents from 2001 to 2016. This paper illustrates evolution of policy themes, evolution of intergovernmental relationships, and evolution of policy relations. This study reveals policy intentions, maps policy progress, and unearths governance philosophy, providing an overall understanding of the policy ways by which the Chinese government has deployed its guiding strategies on professional recycling of e-waste. This paper illustrates how to approach holistic governance from perspective of networked policies, contributing to answering the central question of holistic governance about how to achieve it.

4.
Biol Res ; 53(1): 47, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33066819

RESUMO

Nitrogen is the main limiting nutrient after carbon, hydrogen and oxygen for photosynthetic process, phyto-hormonal, proteomic changes and growth-development of plants to complete its lifecycle. Excessive and inefficient use of N fertilizer results in enhanced crop production costs and atmospheric pollution. Atmospheric nitrogen (71%) in the molecular form is not available for the plants. For world's sustainable food production and atmospheric benefits, there is an urgent need to up-grade nitrogen use efficiency in agricultural farming system. The nitrogen use efficiency is the product of nitrogen uptake efficiency and nitrogen utilization efficiency, it varies from 30.2 to 53.2%. Nitrogen losses are too high, due to excess amount, low plant population, poor application methods etc., which can go up to 70% of total available nitrogen. These losses can be minimized up to 15-30% by adopting improved agronomic approaches such as optimal dosage of nitrogen, application of N by using canopy sensors, maintaining plant population, drip fertigation and legume based intercropping. A few transgenic studies have shown improvement in nitrogen uptake and even increase in biomass. Nitrate reductase, nitrite reductase, glutamine synthetase, glutamine oxoglutarate aminotransferase and asparagine synthetase enzyme have a great role in nitrogen metabolism. However, further studies on carbon-nitrogen metabolism and molecular changes at omic levels are required by using "whole genome sequencing technology" to improve nitrogen use efficiency. This review focus on nitrogen use efficiency that is the major concern of modern days to save economic resources without sacrificing farm yield as well as safety of global environment, i.e. greenhouse gas emissions, ammonium volatilization and nitrate leaching.

5.
Knee ; 27(5): 1560-1566, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-33010774

RESUMO

BACKGROUND: Several suture repair techniques have been reported for radial tear close to the posterior lateral meniscal root (type II PLMRT). However, no study has evaluated the clinical results after repair using the FasT-Fix system. This paper describes a novel H-plasty surgical repair technique and reports its clinical results. METHODS: From January 2015 to January 2017, 47 patients underwent repair of type II PLMRT with concomitant anterior cruciate ligament reconstruction and were included in this study. Assessments performed preoperatively and at final follow-up included the Lysholm score, subjective International Knee Documentation Committee (IKDC) score, and knee stability assessments (pivot-shift test, Lachman test, KNEELAX arthrometer side-to-side difference). Magnetic resonance imaging was used to compare the lateral meniscal extrusion pre- versus postoperatively. Second-look arthroscopy was performed to evaluate the meniscal healing in 38 cases. RESULTS: Forty-seven patients were followed up for an average of 30.7 months (range 18-46 months). No patients experienced meniscal mechanical symptoms. At final follow-up, there were significant improvements in the Lysholm score, IKDC score, knee stability assessments, and lateral meniscal extrusion compared with the preoperative values. In the 38 of 47 patients that underwent second-look arthroscopy after an average of 17.5 months (range 14-19 months), all repairs (100%) were completely healed. CONCLUSIONS: The novel H-plasty repair using the FasT-Fix system was an effective surgical treatment for type II PLMRT. Considering the satisfactory clinical results and the convenience of the surgery, H-plasty repair is recommended to be used preferentially.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33039479

RESUMO

BACKGROUND: Asthma exacerbations are associated with heightened asthma symptoms, which can result in hospitalization in severe cases. However, the molecular immunological processes that determine the course of an exacerbation remains poorly understood, impeding the progression of developing effective therapies. OBJECTIVE: To identify candidate genes that are strongly associated with asthma exacerbation at a cellular level. METHODS: Asthmatic and healthy control subjects were recruited, and bronchoalveolar lavage fluid (BALF) was isolated from these subjects via bronchoscopy. Cells were isolated through FACS, and single-cell RNA sequencing was performed on enriched cell populations. RESULTS: We show that the levels of monocyte, CD8+ T cells, and macrophages are significantly elevated in the BALF of patients. A set of cytokines and intracellular transduction regulators are associated with asthma exacerbations and are shared across multiple cell clusters, forming a complicated molecular framework. An additional group of core exacerbation-associated modules is activated, including EIF2 signaling, Ephrin receptor signaling, and CXCR4 signaling in the subpopulations of CD8+ T cells (C1-a) and monocytes (C7) clusters, which are associated with infection. CONCLUSION: Our study identifies a significant number of severe asthma-associated genes that are differentially expressed by multiple cell clusters CLINICAL IMPLICATIONS: Our study provides an insightful framework to explore, in a clinical setting, the pathogenesis of the disease and identifies therapeutic targets that should be further explored in exacerbation treatments.

7.
BMJ Open ; 10(10): e038879, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33040015

RESUMO

INTRODUCTION: Due to immature brain development, preterm infants are more likely to develop neurological developmental defects compared with full-term infants. Most preterm infants without neurodevelopmental damage can eventually reach the same scholastic level as their same-age peers; however, some show persistent impairment. Breast feeding (BF), which is an important public health measure, is of great significance for preterm infants. Various active substances in breast milk promote the development of the brain and central nervous system in premature infants. We present a protocol for a prospective longitudinal cohort study to explore the effect of in-hospital BF on brain development in preterm infants and possible influencing factors. METHODS AND ANALYSIS: This study will enrol 247 Chinese preterm infants (gestational age: 30-34 weeks) delivered in Women's Hospital School of Medicine, Zhejiang University, and transferred to the neonatal intensive care unit. Demographic, clinical and in-hospital BF data will be collected through electronic medical records. Moreover, follow-up data will be obtained by telephone, interview or online. Measurements will be obtained using the Breastfeeding Self-Efficacy Scale-Short Form, neuroimaging with functional near-infrared spectroscopy, extrauterine growth restriction and the Ages and Stages Questionnaire. Follow-up will be performed at 3, 6 and 12 months after birth. ETHICS AND DISSEMINATION: This study has been approved by the Women's Hospital School of Medicine Zhejiang University Medical Ethics Committee (2019-058). The study results are expected to be published in peer-reviewed journals and reported at relevant national and international conferences. TRIAL REGISTRATION NUMBER: ChiCTR1900027648; Pre-results.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33035679

RESUMO

Myocardin (MYOCD) plays an important role in cardiovascular disease. However, its underlying impact on atherosclerosis remains to be elucidated. ATP binding cassette transporter A1 (ABCA1), a key membrane-associated lipid transporter which maintains intracellular lipid homeostasis, has a protective function in atherosclerosis progress. The purpose of this study was to investigate whether and how the effect of MYOCD on atherosclerosis is associated with ABCA1 in vascular smooth muscle cells (VSMCs). We found both MYOCD and ABCA1 expression were dramatically decreased in atherosclerotic patient aortas compared to control. MYOCD knockdown inhibited ABCA1 expression in human aortic vascular smooth muscle cells (HAVSMCs), leading to reduced cholesterol efflux and increased intracellular cholesterol contents. MYOCD overexpression exerted the opposite effect. Mechanistically, MYOCD regulates ABCA1 expression in an SRF-dependent manner. Consistently, apolipoprotein E-deficient mice treated with MYOCD shRNA developed more plaques in the aortic sinus, which is associated with reduced ABCA1 expression, increased cholesterol retention in the aorta, and decreased high-density lipoprotein cholesterol levels in the plasma. Our data suggest that MYOCD deficiency exacerbates atherosclerosis by downregulating ABCA1 dependent cholesterol efflux from VSMCs, thereby providing a novel strategy for the therapeutic treatment of atherosclerotic cardiovascular disease.

9.
Immunol Rev ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33037700

RESUMO

Unique Vγ2Vδ2 (Vγ9Vδ2) T cells existing only in human and non-human primates, account for the majority of circulating γδ T cells in human adults. Vγ2Vδ2 T cells are the sole γδ T-cell subpopulation capable of recognizing the microbial (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) produced by selected pathogens during infections. Recent seminal studies in non-human primate models have demonstrated that the unique HMBPP-specific Vγ2Vδ2 T cells are fast-acting, multi-functional, and protective during infections. This article reviews the recent seminal observations of Vγ2Vδ2 T cells in protective mechanisms against tuberculosis and other infections.

10.
Int J Mol Med ; 46(5): 1827-1837, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000188

RESUMO

Oxidative stress is one of the main pathogenic factors of neurodegenerative diseases. As the ligand of cannabinoid type 1 (CB1) and 2 (CB2) receptors, anandamide (AEA) exerts benign antioxidant activities. However, the instability of AEA results in low levels in vivo, which limit its further application. Based on the structure of AEA, N­linoleyltyrosine (NITyr) was synthesized in our laboratory and was hypothesized to possess a similar function to that of AEA. To the best of our knowledge, the present study demonstrates for the first time, the activities and mechanisms of NITyr. NITyr treatment attenuated hydrogen peroxide (H2O2)­induced cytotoxicity, with the most promiment effect observed at 1 µmol/l. Treatment with NITyr also suppressed the H2O2­induced elevation of reactive oxygen species (ROS) and enhanced the expression of the autophagy­related proteins, LC3­II, beclin­1, ATG 5 and ATG13. The autophagic inhibitor, 3­methyladenine, reversed the effects of NITyr on ROS levels and cellular viability. Furthermore, AM251, a CB1 receptor antagonist, but not AM630 (a CB2 receptor antagonist), diminished the effects of NITyr on cell viability, ROS generation and autophagy­related protein expression. However, NITyr increased the protein expression of both the CB1 and CB2 receptors. Therefore, NITyr was concluded to protect PC12 cells against H2O2­induced oxidative injury by inducing autophagy, a process which may involve the CB1 receptor.

11.
Medicine (Baltimore) ; 99(40): e22502, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019448

RESUMO

BACKGROUND: Insomnia is a common disease characterized by difficulty falling and/or staying asleep, and accompanied by irritability or fatigue during wakefulness. It is widely reported that insomnia is one of the most extensive mental disorders which the incidence rate is estimated to be about 10%. Insomnia can have serious influences on patients health and quality of life. Electro acupuncture (EA) is reported to be efficacious and widely used for the treatment of insomnia in China. This overview aims to summarize the available evidence from current systematic reviews for the efficacy of electroacupuncture therapy for insomnia. METHODS: We will make a comprehensive retrieval in 7 databases as following:The time is limited from the construction of the library to August 2020. We will use the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) tool to evaluate methodological quality. Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols (PRISMA-P) will be used in the report checklist to assess the quality of reports in the study. The Grading of the Classification of Recommendations, Evaluation, Development and Evaluation (GRADE) will be used to evaluate the included SRs and meta-analysis. Our reviewers will conduct systematic reviews, qualification evaluation, data extraction, methodological quality and evidence quality screening in pairs. The outcomes of interest include: The Pittsburgh Sleep Quality Index (PSQI), The Insomnia Severity Index (ISI), Athens Insomnia Scale, Sleep parameters measured by either subjective or objective approaches, such as actigraphy, polysomnogram, and electroencephalogram. Or any other scale used to assess the level of illness. The evidence will be synthesized where appropriate based on patient subgroups and outcomes. RESULTS: The results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: INPLASY202080087. CONCLUSION: This overview will provide comprehensive evidence of EA for patients with insomnia.

12.
Spectrochim Acta A Mol Biomol Spectrosc ; 246: 119035, 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33049469

RESUMO

Fluorescent pH probes have been served as powerful tools in biological and pathological studies in recent years due to the important roles of pH values in various physiological processes. Although plenty of pH probes have been delivered, development of two-photon ratiometric pH probes with large emission shift for detecting the variation of intracellular pH values is still a greatly challenging task. To address this concern, in this work, we have discovered a general strategy designing pH probes by means of a pH-dependent reversible intramolecular reaction of spiro-oxazolidine which can efficiently change their conjugation length and the electronic effect concurrently. To display the generality of the strategy, we have synthesized six pH probes, and all these probes exhibit short emission in basic conditions and dramatically red-shifted emission in acid environments. The emission shift of the six probes is more than 150 nm and even up to 210 nm, much larger than shift of all commercial and reported pH probes. The chemical sensing mechanism of intramolecular ring opening/closing reaction of spiro-oxazolidine has been confirmed with 1H NMR spectra and density functional theory (DFT) calculations. Finally, we have used one of six with one- and two-photon properties to successfully image lysosomal pH changes under confocal and two-photon microscopes in a ratiometric manner. We believed that this spiro-oxazolidine strategy can serve as a general and powerful platform for the design of ideal pH probes.

13.
Plant Dis ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054622

RESUMO

A total of 707 isolates of Botrytis were collected from plastic tunnel-grown strawberry and tomato in Hubei province of China. They were identified based on the specific molecular markers. Diversity of the B. cinerea (Bc) isolates was evaluated by typing the transposable elements or TE (Boty, Flipper) and the mating types (MAT1-1, MAT1-2), as well as by determining virulence on tobacco (Nicotiana benthamiana) and fenhexamid sensitivity in agar medium. The results showed that 706 isolates (accounting for 99.9%) belonged to Bc, one isolate (accounting for 0.1%) belonged to B. pseudocinerea. The Bc isolates fell into four TE types, Vacuma, Boty, Flipper and Transposa, which accounted for 3.1%, 9.6%, 18.4% and 68.8% (n = 706), respectively. The strawberry and tomato sub-populations of Bc differed significantly (P < 0.05) in composition of the four TE types. The overall ratio of MAT1-1 to MAT1-2 deviated from 1:1 (n = 706, P = 0.0002), MAT1-2 (accounting for 56.9%) predominated over MAT1-1 (accounting for 43.1%). However, in 7 out of 12 geographic sub-populations, the ratio of MAT1-1 to MAT1-2 matched 1:1, whereas in the remaining five geographic sub-populations, the ratio of MAT1-1 to MAT1-2 did not match 1:1. Results of the biological characterizations showed that most Bc isolates were highly sensitive or sensitive to fenhexamid, and the majority of Bc isolates were highly virulent or virulent on tobacco. Moreover, relationship between genetic diversity and biological characteristics was analyzed. The results achieved in this study are helpful for understanding of the populations of B. cinerea.

14.
Food Funct ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33057558

RESUMO

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia mainly due to insulin resistance. The objective of this study was to investigate the effects of polysaccharides from Armillariella tabescens mycelia (AT) on insulin resistance in mice fed a high-fat diet in combination with streptozotocin to induce T2DM. Following treatment with different doses of AT, hyperglycemia and lipid metabolism dysfunction, insulin resistance, and hepatic function-related indices were markedly ameliorated; the histopathological alterations, oxidative stress, and inflammatory reaction in hepatic tissue were also alleviated; most importantly, AT inhibited the expression of hepatic thioredoxin-interacting protein (TXNIP) to repress the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation and activated the 5'AMP-activated protein kinase (AMPK) pathway in a dose-dependent manner in T2DM mice. In conclusion, these findings revealed that the hypoglycemic and hypolipidemic activities of AT were associated with the alleviation of insulin resistance through repression of the TXNIP/NLRP3 inflammasome pathway and activation of the AMPK pathway.

15.
Eur J Nutr ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33068158

RESUMO

PURPOSE: Genistein (GEN) has been reported to have diverse biological activities, including antioxidant, hypolipidemic, and antidiabetic effects. This study investigated whether the ameliorative effects of GEN on inflammation and insulin resistance were associated with the modulation of gut microbiota composition in type 2 diabetic (T2D) mice. METHODS: C57BL/6J mice were treated with a high-fat diet/streptozotocin to induce T2D and then gavaged with GEN (20 and 40 mg/kg) for 8 weeks. Then, oral glucose tolerance, fasting blood glucose, serum insulin, glucagon, lipid profiles, and pro-inflammatory factors were measured. After this, hepatic function and histopathological analysis and inflammation-related indices of the liver and colon were determined, along with short-chain fatty acid (SCFA) and gut microbiota composition. RESULTS: GEN treatment decreased hyperglycemia, hyperlipidemia, and serum pro-inflammatory factor levels and attenuated hepatic dysfunction, pathological changes, inflammation-related protein expression, and hepatocyte apoptosis. It also ameliorated colonic pathological changes, tight junction-associated protein expression, and pro-inflammatory factor increases. Furthermore, high-dose GEN treatment increased the concentrations of SCFAs and down-regulated the ratio of Firmicutes/Bacteroidetes and the abundance of Proteobacteria at the phylum level. However, GEN increased the abundances of Bacteroides and Prevotella and decreased the levels of Helicobacter and Ruminococcus at the genus level in T2D mice. CONCLUSION: GEN showed ameliorative effects on glucose and lipid dysmetabolism and hepatic and colonic dysfunction; most importantly, GEN could ameliorate inflammation and insulin resistance through modulation of gut microbiota composition.

16.
Phys Chem Chem Phys ; 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32895683

RESUMO

van der Waals heterostructures realized by stacking different two-dimensional materials offer the possibility to design new devices with atomic-level precision. The realization of memristive synapses based on full two-dimensional materials provides an avenue for developing neuromorphic computing systems with excellent mechanical flexibility in future. Herein, we first develop the flexible full two-dimensional memristive synapse of graphene/WSe2-xOy/graphene exhibiting stable volatile resistive switching. The oxidation of WSe2 through O2 plasma treatment plays a key role in improving the memristive performance of the devices. And the switching behavior is associated with the migration of oxygen vacancies at the graphene/WSe2-xOy interface. Versatile synaptic functions have been realized, including short-term plasticity, long-term plasticity, the transition from short-term plasticity to long-term plasticity and high-pass temporal filtering, with ultralow energy consumption of ∼16.1 pJ per spike. The flexible full two-dimensional devices fabricated on flexible polyimide substrate show excellent mechanical flexibility, including a good endurance against repeatable bending of 1000 times and a bending strain of 2.5%.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32900922

RESUMO

The electronic Seebeck response in a conductor involves the energy-dependent mean free path of the charge carriers and is affected by crystal structure, scattering from boundaries and defects, and strain. Previous photothermoelectric (PTE) studies have suggested that the thermoelectric properties of polycrystalline metal nanowires are related to grain structure, although direct evidence linking crystal microstructure to the PTE response is difficult to elucidate. Here, we show that room temperature scanning PTE measurements are sensitive probes that can detect subtle changes in the local Seebeck coefficient of gold tied to the underlying defects and strain that mediate crystal deformation. This connection is revealed through a combination of scanning PTE and electron microscopy measurements of single-crystal and bicrystal gold microscale devices. Unexpectedly, the photovoltage maps strongly correlate with gradually varying crystallographic misorientations detected by electron backscatter diffraction. The effects of individual grain boundaries and differing grain orientations on the PTE signal are minimal. This scanning PTE technique shows promise for identifying minor structural distortions in nanoscale materials and devices.

18.
Sci Adv ; 6(37)2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32917690

RESUMO

Biodiversity loss is a social and ecological emergency, and calls have been made for the global expansion of protected areas (PAs) to tackle this crisis. It is unclear, however, where best to locate new PAs to protect biodiversity cost-effectively. To answer this question, we conducted a spatial meta-analysis by overlaying seven global biodiversity templates to identify conservation priority zones. These are then combined with low human impact areas to identify cost-effective zones (CEZs) for PA designation. CEZs cover around 38% of global terrestrial area, of which only 24% is currently covered by existing PAs. To protect more CEZs, we propose three scenarios with conservative, moderate, and ambitious targets, which aim to protect 19, 26, and 43% of global terrestrial area, respectively. These three targets are set for each Convention on Biological Diversity party with spatially explicit CEZs identified, providing valuable decision support for the post-2020 global biodiversity framework.

19.
Science ; 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32972995

RESUMO

Clinical outcome upon infection with SARS-CoV-2 ranges from silent infection to lethal COVID-19. We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern TLR3- and IRF7-dependent type I interferon (IFN) immunity to influenza virus, in 659 patients with life-threatening COVID-19 pneumonia, relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally define LOF variants in 23 patients (3.5%), aged 17 to 77 years, underlying autosomal recessive or dominant deficiencies. We show that human fibroblasts with mutations affecting this pathway are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.

20.
Signal Transduct Target Ther ; 5(1): 197, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32994405

RESUMO

Posttranslational modifications (PTMs) of proteins, including chromatin modifiers, play crucial roles in the dynamic alteration of various protein properties and functions including stem-cell properties. However, the roles of Lymphoid-specific helicase (LSH), a DNA methylation modifier, in modulating stem-like properties in cancer are still not clearly clarified. Therefore, exploring PTMs modulation of LSH activity will be of great significance to further understand the function and activity of LSH. Here, we demonstrate that LSH is capable to undergo PTMs, including methylation and phosphorylation. The arginine methyltransferase PRMT5 can methylate LSH at R309 residue, meanwhile, LSH could as well be phosphorylated by MAPK1 kinase at S503 residue. We further show that the accumulation of phosphorylation of LSH at S503 site exhibits downregulation of LSH methylation at R309 residue, which eventually promoting stem-like properties in lung cancer. Whereas, phosphorylation-deficient LSH S503A mutant promotes the accumulation of LSH methylation at R309 residue and attenuates stem-like properties, indicating the critical roles of LSH PTMs in modulating stem-like properties. Thus, our study highlights the importance of the crosstalk between LSH PTMs in determining its activity and function in lung cancer stem-cell maintenance.

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