Publications by authors named "Xiao Liu"

2,106 Publications

  • Page 1 of 1

Molecular cloning and biochemical characterization of a new coumarin glycosyltransferase CtUGT1 from Cistanche tubulosa.

Fitoterapia 2021 Jul 19:104995. Epub 2021 Jul 19.

Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, People's Republic of China. Electronic address:

UDP-glycosyltransferases (UGTs) are an important and functionally diverse family of enzymes involved in secondary metabolite biosynthesis. Coumarin is one of the most common skeletons of natural products with candidate pharmacological activities. However, to date, many reported GTs from plants mainly recognized flavonoids as sugar acceptors. Only limited GTs could catalyze the glycosylation of coumarins. In this study, a new UGT was cloned from Cistanche tubulosa, a valuable traditional tonic Chinese herb, which is abundant with diverse glycosides such as phenylethanoid glycosides, lignan glycosides, and iridoid glycosides. Sequence alignment and phylogenetic analysis showed that CtUGT1 is phylogenetically distant from most of the reported flavonoid UGTs and adjacent to phenylpropanoid UGTs. Extensive in vitro enzyme assays found that although CtUGT1 was not involved in the biosynthesis of bioactive glycosides in C. tubulosa, it could catalyze the glucosylation of coumarins umbelliferone 1, esculetine 2, and hymecromone 3 in considerable yield. The glycosylated products were identified by comparison with the reference standards or NMR spectroscopy, and the results indicated that CtUGT1 can regiospecifically catalyze the glucosylation of hydroxyl coumarins at C7-OH position. The key residues that determined CtUGT1's activity were further discussed based on homology modeling and molecular docking analyses. Combined with site-directed mutagenesis results, it was found that H19 played an irreplaceable role as the crucial catalysis basis. CtUGT1 could be used in the enzymatic preparation of bioactive coumarin glycosides.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fitote.2021.104995DOI Listing
July 2021

A Stromal Tumor Presenting as a Pseudoaneurysmal Dilation of the Small Bowel Mimicking a Lymphoma on FDG PET/CT.

Clin Nucl Med 2021 Jul 20. Epub 2021 Jul 20.

From the Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.

Abstract: An 84-year-old woman visited our hospital with hematochezia for 1 month. Abdominal CT and FDG PET/CT showed local thickening of the small intestine, resembling an intestinal aneurysmal dilatation. Thus, a lymphoma was suspected, and surgical resection was performed. The final pathology revealed an exophytic small bowel stromal tumor with perforation, causing pseudoaneurysmal dilation of the small bowel. This case emphasized the importance of considering a small bowel stromal tumor when faced with similar FDG PET/CT findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/RLU.0000000000003832DOI Listing
July 2021

Ultrasonic characterization of localized passive elastic properties of human pennate muscle with a single-probe setup.

Ultrasonics 2021 Jul 8;116:106512. Epub 2021 Jul 8.

Department of Ultrasonography, Shenzhen Hospital of Guangzhou University of Chinese Medicine, Shenzhen 518034, China.

Quantitative evaluation of passive elastic properties of an individual skeletal muscle in vivo is among the major challenges of biomechanics, and its clinical application is severely limited. By combining shear-wave elastography (SWE) and B-mode imaging techniques, this study develops a novel non-invasive method to measure the local elastic modulus-fascicle strain curve of human pennation muscle during passive stretching using a single probe. Physiologically meaningful parameters are estimated and compared in subjects with different ages or pathological conditions. The in vivo experimental group comprised 12 healthy subjects (four children, four adults, and four seniors) and eight patients (four suffering from pseudohypertrophy, four from atrophy). Their gastrocnemius muscles were passively stretched using an ankle joint motion instrument. Local elastic moduli of the muscle were measured using SWE imaging frames and a built-in 'F-ROI' tool. The corresponding fascicle strains were simultaneously obtained using B-mode imaging frames and a gradient Radon transform. Three parameters (η, μ, G) were estimated from a normalized elastic modulus-strain curve using the Gauss-Newton method. The measured elastic modulus-strain curves all agreed with models of the estimated parameters (0.910 < R < 0.999) and presented different patterns among normal and diseased subjects. η values were lower for pseudohypertrophies (1.93 ± 0.12), but higher for atrophies (63.40 ± 98.89), compared with normal ones (6.02 ± 2.53). In addition, μ values were higher for pseudohypertrophies (22.65 ± 16.40), but lower for atrophies (0.28 ± 0.41), compared with normal ones (1.07 ± 1.22). The proposed method may provide novel insight into the biomechanics of pennate muscle and has the potential to serve for clinical musculoskeletal medical diagnosis, as the single-probe scanning setup is broadly accepted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ultras.2021.106512DOI Listing
July 2021

Hypercholesterolemia risk associated Abca6 does not regulate lipoprotein metabolism in mice or hamster.

Biochim Biophys Acta Mol Cell Biol Lipids 2021 Jul 16;1866(11):159006. Epub 2021 Jul 16.

Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan 430072, People's Republic of China. Electronic address:

Hypercholesterolemia has strong heritability and about 40-60% of hypercholesterolemia is caused by genetic risk factors. A number of monogenic genes have been identified so far for familial hypercholesterolemia (FH). However, in the general population, more than 90% of individuals with LDL cholesterol over 190 mg/dL do not carry known FH mutations. Large scale whole-exome sequencing has identified thousands of variants that are predicted to be loss-of-function (LoF) and each individual has a median of about twenty rare LoF variants and several hundreds more common LoF variants. However, majority of those variants have not been characterized and their functional consequence remains largely unknown. Rs77542162 is a common missense variant in ABCA6 and is strongly associated with hypercholesterolemia in different populations. ABCA6 is a cholesterol responsive gene and has been suggested to play a role in lipid metabolism. However, whether and how rs77542162 and ABCA6 regulate lipoprotein metabolism remain unknown. In current study, we systemically characterized the function of rs77542162 and ABCA6 in cultured cells and in vivo of rodents. We found that Abca6 is specifically expressed on the basolateral surface of hepatocytes in mouse liver. The rs77542162 variant disrupts ABCA6 protein stability and results in loss of functional protein. However, we found no evidence that Abca6 plays a role in lipoprotein metabolism in either normal mice or hypercholesterolemia mice or hamsters. Thus, our results suggest that Abca6 does not regulate lipoprotein metabolism in rodents and highlight the challenge and importance of functional characterization of disease-associated variants in animal models.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbalip.2021.159006DOI Listing
July 2021

Utilisation of machine learning to predict surgical candidates for the treatment of childhood upper airway obstruction.

Sleep Breath 2021 Jul 17. Epub 2021 Jul 17.

School of Electrical and Electronic Engineering, The University of Adelaide, Adelaide, SA, 5005, Australia.

Objective: To investigate the effect of adenotonsillectomy on OSAS symptoms based on a data-driven approach and thereby identify criteria that may help avoid unnecessary surgery in children with OSAS.

Methods: In 323 children enrolled in the Childhood Adenotonsillectomy Trial, randomised to undergo either early adenotonsillectomy (eAT; N = 165) or a strategy of watchful waiting with supportive care (WWSC; N = 158), the apnea-hypopnea index, heart period pattern dynamics, and thoraco-abdominal asynchrony measurements from overnight polysomnography (PSG) were measured. Using machine learning, all children were classified into one of two different clusters based on those features. The cluster transitions between follow-up and baseline PSG were investigated for each to predict those children who recovered spontaneously, following surgery and those who did not benefit from surgery.

Results: The two clusters showed significant differences in OSAS symptoms, where children assigned in cluster A had fewer physiological and neurophysiological symptoms than cluster B. Whilst the majority of children were assigned to cluster A, those children who underwent surgery were more likely to stay in cluster A after seven months. Those children who were in cluster B at baseline PSG were more likely to have their symptoms reversed via surgery. Children who were assigned to cluster B at both baseline and 7 months after surgery had significantly higher end-tidal carbon dioxide at baseline. Children who spontaneously changed from cluster B to A presented highly problematic ratings in behaviour and emotional regulation at baseline.

Conclusions: Data-driven analysis demonstrated that AT helps to reverse and to prevent the worsening of the pathophysiological symptoms in children with OSAS. Multiple pathophysiological markers used with machine learning can capture more comprehensive information on childhood OSAS. Children with mild physiological and neurophysiological symptoms could avoid AT, and children who have UAO symptoms post AT may have sleep-related hypoventilation disease which requires further investigation. Furthermore, the findings may help surgeons more accurately predict children on whom they should perform AT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11325-021-02425-wDOI Listing
July 2021

Characteristic, hazard and iron recovery technology of red mud - A critical review.

J Hazard Mater 2021 Jul 1;420:126542. Epub 2021 Jul 1.

School of Resources and Civil Engineering, Northeastern University, Shenyang 110819, PR China; National-Local Joint Engineering Research Center of High-Efficient Exploitation Technology for Refractory Iron Ore Resources, Shenyang 110819, PR China.

Red mud (RM) is the major waste material with strong alkaline discharged which is during the alumina extraction process. The global stock of RM has exceeded 4 billion tons and its disposal as a solid waste has always been a thorny environmental problem. However, RM is widely considered to be a potential resource due to its high content of valuable metal components such as iron. High-iron RM is rich in iron and can potentially become a valuable resource if the iron can be extracted effectively. It is of great research value and profound significance to recover iron from high-iron RM. This paper systematically reviews the iron recovery methods for resource utilization of high-iron RM, and divides the technology of iron recovery from high-iron RM into three aspects: physical separation method, pyrometallurgy method (reduction smelting and reduction roasting) and hydrometallurgy method (acid leaching). The basic principles and effect of iron extraction of the above technologies are summarized respectively, and the advantages and disadvantages of different technologies are compared. It is pointed out that the feasibility and economic cost are the main factor restricting the industrial application of these technologies. Therefore, it is of great significance to overcome various problems and difficulties, and develop innovative processes and technologies, which can realize the recycling and utilization of iron in high-iron RM and realize the reduction of RM emission at the same time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhazmat.2021.126542DOI Listing
July 2021

Neoadjuvant chemoradiotherapy plus postoperative adjuvant XELOX chemotherapy versus postoperative adjuvant chemotherapy with XELOX regimen for local advanced gastric cancer-A randomized, controlled study.

Br J Radiol 2021 Aug 14;94(1124):20201088. Epub 2021 Jul 14.

Department of Oncology, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Objective: The aim of this study was to compare the clinical efficacy of neoadjuvant chemoradiotherapy (NACRT) combined with postoperative adjuvant XELOX (Oxaliplatin +Capecitabine) chemotherapy and postoperative adjuvant chemotherapy (ACT) with XELOX for local advanced gastric cancer (LAGC).

Methods: In this prospectively randomized trial, we investigated the effect of NACRT combined with postoperative ACT for LAGC. 60 patients were randomly divided into NACRT group and ACT group, with 30 patients in each group. Patients in NACRT group were given three-dimensional conformal radiotherapy (45 Gy/1.8 Gy/f) accompanied by synchronous XELOX of two cycles, followed by surgery, and then postoperative adjuvant XELOX chemotherapy of four cycles was performed. Patients in ACT group received surgery in advance, and then XELOX chemotherapy of six cycles was given.

Results: The objective response rate of NACRT was 76.7%. The overall incidence of postoperative complications in NACRT group was not significantly different from that in ACT group (23.1% 30.0%, = 0.560). The 1 year, 2 years, and 3 years progression-free survival (PFS)and overall survival (OS) in NACRT and ACT groups were 80.0% 56.7%, 73.3% 46.7%, 60.0% 33.3%, and 86.7% 80.0%, 76.7% 66.7%, 63.3% 50.0%, respectively. Patients in NACRT group showed a significantly higher R0 resection rate (84.6% 56.7%, = 0.029),lower loco-regional recurrence rate (36.7% 11.5%, = 0.039), longer PFS ( = 0.019) and freedom from locoregional progression(FFLP) ( = 0.004) than patients in ACT group, while there was no difference in OS ( = 0.215) and in toxicity incidence ( > 0.05).

Conclusions: NACRT combined with postoperative adjuvant XELOX chemotherapy can improve R0 resection rate, reduce loco-regional recurrence, prolong PFS and FFLP without increasing the incidence of postoperative complications in patients with LAGC.

Advances In Knowledge: Compared with postoperative adjuvant chemotherapy, locally advanced gastric cancer patients may benefit from neoadjuvant chemoradiotherapy, and toxicity associated with chemoradiotherapy was tolerant and manageable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1259/bjr.20201088DOI Listing
August 2021

Immunotherapy-based targeting of MSLN activated portal fibroblasts is a strategy for treatment of cholestatic liver fibrosis.

Proc Natl Acad Sci U S A 2021 Jul;118(29)

Department of Surgery, University of California San Diego Medical Center, La Jolla, CA 92161;

We investigated the role of mesothelin (Msln) and thymocyte differentiation antigen 1 (Thy1) in the activation of fibroblasts across multiple organs and demonstrated that Msln mice are protected from cholestatic fibrosis caused by Mdr2 (multidrug resistance gene 2) deficiency, bleomycin-induced lung fibrosis, and UUO (unilateral urinary obstruction)-induced kidney fibrosis. On the contrary, Thy1 mice are more susceptible to fibrosis, suggesting that a Msln-Thy1 signaling complex is critical for tissue fibroblast activation. A similar mechanism was observed in human activated portal fibroblasts (aPFs). Targeting of human MSLN aPFs with two anti-MSLN immunotoxins killed fibroblasts engineered to express human mesothelin and reduced collagen deposition in livers of bile duct ligation (BDL)-injured mice. We provide evidence that antimesothelin-based therapy may be a strategy for treatment of parenchymal organ fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2101270118DOI Listing
July 2021

GmPIN-dependent polar auxin transport is involved in soybean nodule development.

Plant Cell 2021 Jul 7. Epub 2021 Jul 7.

Haixia Institute of Science and Technology, Horticultural Plant Biology and Metabolomics Center, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China.

To overcome nitrogen deficiency, legume roots establish symbiotic interactions with nitrogen-fixing rhizobia that is fostered in specialized organs (nodules). Similar to other organs, nodule formation is determined by a local maximum of the phytohormone auxin at the primordium site. However, how auxin regulates nodule development remains poorly understood. Here, we found that in soybean, (Glycine max), dynamic auxin transport driven by PIN-FORMED (PIN) transporter GmPIN1 is involved in nodule primordium formation. GmPIN1 was specifically expressed in nodule primordium cells and GmPIN1 was polarly localized in these cells. Two nodulation regulators, (iso)flavonoids trigger expanded distribution of GmPIN1b to root cortical cells, and cytokinin rearranges GmPIN1b polarity. Gmpin1abc triple mutants generated with CRISPR-Cas9 showed impaired establishment of auxin maxima in nodule meristems and aberrant divisions in the nodule primordium cells. Moreover, overexpression of GmPIN1 suppressed nodule primordium initiation. GmPIN9d, an ortholog of Arabidopsis thaliana PIN2, acts together with GmPIN1 later in nodule development to acropetally transport auxin in vascular bundles, fine-tuning the auxin supply for nodule enlargement. Our findings reveal how PIN-dependent auxin transport modulates different aspects of soybean nodule development and suggest that establishment of auxin gradient is a prerequisite for the proper interaction between legumes and rhizobia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/plcell/koab183DOI Listing
July 2021

iTRAQ-based quantitative proteomic analysis of the hepatopancreas in Scylla paramamosain during the molting cycle.

Comp Biochem Physiol Part D Genomics Proteomics 2021 Jul 1;40:100870. Epub 2021 Jul 1.

School of Marine Science, Ningbo University, Ningbo, Zhejiang 315832, China. Electronic address:

The hepatopancreas is the key organ involved in energy storage, immune response, and metabolism during crustacean molting, yet the underlying molecular mechanisms in the hepatopancreas that regulate molting remain unknown. In the present study, we conducted a comprehensive proteomic analysis in the hepatopancreas and quantified 1527 proteins, of which 193 changed significantly in abundance among three molting stages (pre-molt: PrM, post-molt: PoM, and inter-molt: InM) of Scylla paramamosain using iTRAQ-coupled LC-MS/MS. Ten exoskeleton and cuticle reconstruction proteins, such as chitinase, cuticle protein and myosin heavy chain, were found change significantly in abundance between PoM and PrM. Six energy metabolism proteins such as mitochondrial cytochrome c oxidase, cytochrome b-c1 and cAMP-dependent protein kinase with positive loadings showed a higher abundance in InM than PoM. In addition, all differentially abundance proteins (DAPs) were annotated for GO function and KEGG pathway analysis. GO analysis demonstrated function subcategories mainly including thiamine metabolism, complement and coagulation cascades, endocrine, shigellosis, salmonella infection, and other factor-regulated calcium reabsorption. The KEGG pathway enrichment analysis indicated that the DAPs were mainly involved in reconstruction of the exoskeleton and cuticle, energy reserves, metabolism, and immune response during the molting process. The results for the proteins and key pathways involved in the molting process provide fundamental molecular evidence that will improve our understanding of morphological and metabolism variation in the molting cycle and will serve as a potential blueprint for future study on molecular mechanism of molting in crustaceans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cbd.2021.100870DOI Listing
July 2021

The safety of morphine in patients with acute heart failure: A systematic review and meta-analysis.

Clin Cardiol 2021 Jul 8. Epub 2021 Jul 8.

Cardiology Department, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

While morphine has long been widely used in treating acute heart failure (AHF) due to its vasodilatory properties and anticipated anxiolysis, it remains unclear whether the application of morphine to those patients is reasonable. We aim to conduct a systematic review and meta-analysis to assess the safety of morphine in patients with AHF. We searched PubMed, Cochrane Library, and Embase electronic databases from inception through March 2020. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the outcomes. Seven studies with 172, 226 patients were included. The results showed that morphine usage was not associated with increased in-hospital mortality (OR: 1.94; 95% CI 0.93 to 4.03; p = 0.08). However, the use of morphine significantly increased the risk of invasive ventilation (OR: 2.72; 95% CI 1.09 to 6.80; p = 0.03). Furthermore, the subgroup analysis indicated that the application of morphine was not associated with increased 7-day all-cause mortality in patients with AHF (OR: 1.69; 95% CI 0.80 to 3.22; p = 0.11) but significantly increased the risk of 30-day all-cause mortality (OR: 1.59; 95% CI 1.16 to 2.17; p = 0.004). Based on current evidence, our results suggested that although morphine therapy did not significantly increase the risk of short-term death (in the hospital or within 7 days) in patients with AHF, the risk of long-term death and invasive ventilation were significantly increased. This result needs to be further confirmed by an ongoing randomized control trial.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/clc.23691DOI Listing
July 2021

Definitive Simultaneous Integrated Boost Versus Conventional-Fractionated Intensity Modulated Radiotherapy for Patients With Advanced Esophageal Squamous Cell Carcinoma: A Propensity Score-Matched Analysis.

Front Oncol 2021 21;11:618776. Epub 2021 Jun 21.

Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: The aim of this study was to compare the effects of simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT) and conventional fractionated-IMRT (CF-IMRT) for patients with esophageal squamous cell carcinoma (ESCC).

Methods: The data of 1173 patients treated with either CF-IMRT or SIB-IMRT for a curative intent from 2005 to 2016 were retrospectively reviewed. Propensity score matching (PSM) was used to create a well-balanced cohort of 687 patients at 1:2 ratio (237 patients in SIB-IMRT group and 450 patients in CF-IMRT group). Overall survival (OS), progression-free survival (PFS), recurrence pattern, and toxicity profiles were evaluated and compared between the two groups after PSM.

Results: After a median follow-up time of 42.3 months (range, 3.0-153.2 months) for surviving patients, survival results were comparable in the two groups. After PSM, the 1-year, 2-year and 4-year OS rates in the SIB-IMRT and CF-IMRT groups were 70.0% 66.4%, 41.9% 41.7% and 30.2% 27.6%, respectively ( = 0.87). The 1-year, 2-year and 4-year PFS rates were 48.4% 49.1%, 31.2% 29.4%, and 26.1% 17.9%, respectively ( = 0.64). Locoregional recurrence ( = 0.32) and distant metastasis ( = 0.54) rates were also comparable between two groups. The toxicity profile was similar in the two groups. Multivariate analyses in the matched samples showed that female, concurrent chemotherapy and earlier clinical stage were independently associated with longer OS and PFS.

Conclusions: SIB-IMRT appears to be equivalent to CF-IMRT in treatment efficacy and safety, and could become an alternative option for definitive radiotherapy of ESCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.618776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256744PMC
June 2021

Simultaneous Determination of a Novel PD-L1 Inhibitor, IMMH-010, and Its Active Metabolite, YPD-29B, in Rat Biological Matrices by Polarity-Switching Liquid Chromatography-Tandem Mass Spectrometry: Application to ADME Studies.

Front Pharmacol 2021 21;12:677120. Epub 2021 Jun 21.

Department of Drug Metabolism, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

IMMH-010 is a prodrug of YPD-29B, which is a novel PD-L1 inhibitor. A specific and sensitive LC-MS/MS method with polarity switching was developed and validated for the simultaneous determination of IMMH-010 and YPD-29B in rat plasma, liver, brain, urine and fecal samples. Method validation was investigated to demonstrate the lower limit of quantification linearity, precision and accuracy, matrix effect and recovery, stability and dilution reliability for IMMH-010 and YPD-29B. This validated method was successfully applied to investigate the pharmacokinetics, tissue distribution, and excretion of IMMH-010 and YPD-29B in rats. After oral administration of IMMH-010 maleate to rats, IMMH-010 was rapidly and extensively converted to the active metabolite YPD-29B. The areas under the plasma concentration-time curve (AUC) of IMMH-010 and YPD-29B were proportional to the dose in the range of 10-100 mg/kg. IMMH-010 was primarily distributed in the adrenal gland, lymph nodes, heart, liver and spleen. YPD-29B was mainly observed in the liver, lymph, kidney, and lung. Approximately 28.81% of the IMMH-010 dose was recovered in the urine and feces within 72 h, including unchanged IMMH-010 (7.99%) and YPD-29B (20.82%). The results of this study may be useful as a reference for further development of IMMH-010 and PD-L1 inhibitors. : [https://clinicaltrials.gov/ct2/show/NCT04343859?term=IMMH-010&draw=2&rank=1], identifier [NCT04343859]."
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.677120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256334PMC
June 2021

The Main Progress of Perovskite Solar Cells in 2020-2021.

Nanomicro Lett 2021 Jul 7;13(1):152. Epub 2021 Jul 7.

State Key Laboratory of Metal Matrix Composites, School of Material Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.

Perovskite solar cells (PSCs) emerging as a promising photovoltaic technology with high efficiency and low manufacturing cost have attracted the attention from all over the world. Both the efficiency and stability of PSCs have increased steadily in recent years, and the research on reducing lead leakage and developing eco-friendly lead-free perovskites pushes forward the commercialization of PSCs step by step. This review summarizes the main progress of PSCs in 2020 and 2021 from the aspects of efficiency, stability, perovskite-based tandem devices, and lead-free PSCs. Moreover, a brief discussion on the development of PSC modules and its challenges toward practical application is provided.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40820-021-00672-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263824PMC
July 2021

[Production of curcumin by engineered Escherichia coli].

Sheng Wu Gong Cheng Xue Bao 2021 Jun;37(6):2077-2084

Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.

Curcumin is exclusively isolated from Zingiberaceae plants with a broad spectrum of bioactivities. In the present study, we used the diketide-CoA synthase (DCS) and curcumin synthase (CURS) genes to construct a non-natural fusion gene encoding diketide-CoA synthase::curcumin synthase (DCS::CURS). This fusion protein, together with the acetyl coenzyme A carboxylase (ACC) and the 4-coumarate coenzyme A ligase (4CL), were introduced into Escherichia coli for the production of curcumin from ferulic acid. The process is divided into two stages, the growth stage using LB medium and the fermentation stage using the modified M9 medium. The yield of curcumin reached 386.8 mg/L by optimizing the induction of protein expression in the growth stage, and optimizing the inoculum volume, medium composition and fermentation time in the fermentation stage, as well as the addition of macroporous resin AB-8 into the second medium to attenuate the toxicity of the end product. The exploitation of the non-natural fusion protein DCS::CURS for the production of curcumin provides a new alternative to further promoting the production of curcumin and the related analogues.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.13345/j.cjb.200825DOI Listing
June 2021

Pneumonia caused by Pseudomonas fluorescens: a case report.

BMC Pulm Med 2021 Jul 5;21(1):212. Epub 2021 Jul 5.

Department of Pulmonary and Critical Care Medicine, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012, China.

Background: Pseudomonas fluorescens (P. fluorescens) has been detected in respiratory samples from patients. However, no previous reports have been published about these P. fluorescens cultures from lung tissues.

Case Presentation: Here, we report a case of pneumonia caused by P. fluorescens. P. fluorescens was identified from lung biopsy specimens for the first time in this case. According to the antibiotic susceptibility testing (AST) of P. fluorescens, the patient was given ciprofloxacin treatment. The temperature of the patient then returned to normal. Chest CT examination revealed improvements in pulmonary inflammation.

Conclusions: These findings suggest that the patients with pneumonia caused by P. fluorescens should be treated in a timely manner according to the AST results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12890-021-01573-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259381PMC
July 2021

Coronary artery calcification and risk of mortality and adverse outcomes in patients with COVID-19: a Chinese multicenter retrospective cohort study.

Chin J Acad Radiol 2021 Jun 28:1-9. Epub 2021 Jun 28.

Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nanjing, 210002 Jiangsu Province People's Republic of China.

Background: Coronary artery calcification (CAC) is an independent risk factor of major adverse cardiovascular events; however, the impact of CAC on in-hospital death and adverse clinical outcomes in patients with coronavirus disease 2019 (COVID-19) remains unclear.

Objective: To explore the association between CAC and in-hospital mortality and adverse events in patients with COVID-19.

Methods: This multicenter retrospective cohort study enrolled 2067 laboratory-confirmed COVID-19 patients with definitive clinical outcomes (death or discharge) admitted from 22 tertiary hospitals in China between January 3, 2020 and April 2, 2020. Demographic, clinical, laboratory results, chest CT findings, and CAC on admission were collected. The primary outcome was in-hospital death and the secondary outcome was composed of in-hospital death, admission to intensive care unit (ICU), and requiring mechanical ventilation. Multivariable Cox regression analysis and Kaplan-Meier plots were used to explore the association between CAC and in-hospital death and adverse clinical outcomes.

Results: The mean age was 50 years (SD,16) and 1097 (53.1%) were male. A total of 177 patients showed high CAC level, and compared with patients with low CAC, these patients were older (mean age: 49 vs. 69 years,  < 0.001) and more likely to be male (52.0% vs. 65.0%,  = 0.001). Comorbidities, including cardiovascular disease (CVD) ([33.3%, 59/177] vs. [4.7%, 89/1890],  < 0.001), presented more often among patients with high CAC, compared with patients with low CAC. As for laboratory results, patients with high CAC had higher rates of increased D-dimer, LDH, as well as CK-MB (all  < 0.05). The mean CT severity score in high CAC group was also higher than low CAC group (12.6 vs. 11.1,  = 0.005). In multivariable Cox regression model, patients with high CAC were at a higher risk of in-hospital death (hazard ratio [HR], 1.731; 95% CI 1.010-2.971,  = 0.046) and adverse clinical outcomes (HR, 1.611; 95% CL 1.087-2.387,  = 0.018).

Conclusion: High CAC is a risk factor associated with in-hospital death and adverse clinical outcomes in patients with confirmed COVID-19, which highlights the importance of calcium load testing for hospitalized COVID-19 patients and calls for attention to patients with high CAC.

Supplementary Information: The online version contains supplementary material available at 10.1007/s42058-021-00072-4.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s42058-021-00072-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237549PMC
June 2021

Characterization of a ferroptosis and iron-metabolism related lncRNA signature in lung adenocarcinoma.

Cancer Cell Int 2021 Jul 3;21(1):340. Epub 2021 Jul 3.

Department of Pulmonary and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China.

Background: Long non-coding RNAs (lncRNAs) are increasingly recognized as the crucial mediators in the regulation of ferroptosis and iron metabolism. A systematic understanding of ferroptosis and iron-metabolism related lncRNAs (FIRLs) in lung adenocarcinoma (LUAD) is essential for new diagnostic and therapeutic strategies.

Methods: FIRLs were obtained through Pearson correlation analysis between ferroptosis and iron-metabolism related genes and all lncRNAs. Univariate and multivariate Cox regression analysis were used to identify optimal prognostic lncRNAs. Next, a novel signature was constructed and risk score of each patient was calculated. Survival analysis and ROC analysis were performed to evaluate the predictive performance using The Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) and Gene Expression Omnibus (GEO) datasets, respectively. Furthermore, multivariate Cox and stratification analysis were used to assess prognostic value of this signature in whole cohort and various subgroups. The correlation of risk signature with immune infiltration and gene mutation was also discussed. The expression of lncRNAs was verified by quantitative real-time PCR (qRT-PCR).

Results: A 7-FIRLs signature including ARHGEF26-AS1, LINC01137, C20orf197, MGC32805, TMPO-AS1, LINC00324, and LINC01116 was established in the present study to assess the overall survival (OS) of LUAD. The survival analysis and ROC curve indicated good predictive performance of the signature in both the TCGA training set and the GEO validation set. Multivariate Cox and stratification analysis indicated that the 7-FIRLs signature was an independent prognostic factor for OS. Nomogram exhibited robust validity in prognostic prediction. Differences in immune cells, immune functions and gene mutation were also found between high-risk and low-risk groups.

Conclusions: This risk signature based on the FIRLs may be promising for the clinical prediction of prognosis and immunotherapeutic responses in LUAD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12935-021-02027-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254945PMC
July 2021

FRQ-CK1 Interaction Underlies Temperature Compensation of the Circadian Clock.

mBio 2021 06 29;12(3):e0142521. Epub 2021 Jun 29.

State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.

Temperature compensation is a fundamental property of all circadian clocks; temperature compensation results in a relatively constant period length at different physiological temperatures, but its mechanism is unclear. Formation of a stable complex between clock proteins and casein kinase 1 (CK1) is a conserved feature in eukaryotic circadian mechanisms. Here, we show that the FRQ-CK1 interaction and CK1-mediated FRQ phosphorylation, not FRQ stability, are main mechanisms responsible for the circadian temperature compensation phenotypes in . Inhibition of CK1 kinase activity impaired the temperature compensation profile. Importantly, both the loss of temperature compensation and temperature overcompensation phenotypes of the wild-type and different clock mutant strains can be explained by temperature-dependent alterations of the FRQ-CK1 interaction. Furthermore, mutations that were designed to specifically affect the FRQ-CK1 interaction resulted in impaired temperature compensation of the clock. Together, these results reveal the temperature-compensated FRQ-CK1 interaction, which results in temperature-compensated CK1-mediated FRQ and WC phosphorylation, as a main biochemical process that underlies the mechanism of circadian temperature compensation in . Temperature compensation allows clocks to adapt to all seasons by having a relatively constant period length at different physiological temperatures, but the mechanism of temperature compensation is unclear. Stability of clock proteins was previously proposed to be a major factor that regulated temperature compensation. In this study, we showed that the interaction between CK1 and FRQ, but not FRQ stability, explains the circadian temperature compensation phenotypes in . This study uncovered the key biochemical mechanism responsible for temperature compensation of the circadian clock and further established the mechanism for period length determination in . Because the regulation of circadian clock proteins by CK1 and the formation of a stable clock complex with CK1 are highly conserved in eukaryotic clocks, a similar mechanism may also exist in animal clocks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/mBio.01425-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263009PMC
June 2021

Protective role of sirtuin3 against oxidative stress and NLRP3 inflammasome in cholesterol accumulation and foam cell formation of macrophages with ox-LDL-stimulation.

Biochem Pharmacol 2021 Jun 25;192:114665. Epub 2021 Jun 25.

Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, Jiangsu, China. Electronic address:

Sirtuin3 (SIRT3) is involved in reactive oxygen species (ROS), cell metabolism, apoptosis and inflammation. However, the exact role of SIRT3 in macrophages during pathophysiological process of atherosclerosis remains unclear. The present study was to investigate the possible effects and mechanisms of SIRT3 on lipid uptake and foam cells transforming in oxidized low-density lipoprotein (ox-LDL)-stimulated macrophages. Compared with wild-type (WT) mice, SIRT3 deficiency further increased foam cell formation and cellular cholesterol accumulation, exacerbated oxidative stress, impaired mitochondrial permeability potential, decreased optic atrophy 1 (OPA1) but enhanced dynamin-related protein 1 (DRP1) expression, and promoted NLR family pyrin domain-containing protein 3 (NLRP3) activation in ox-LDL-stimulated macrophages from SIRT3 knockout (KO) mice. Dihydromyricetin (DMY), a potential compound to enhance SIRT3 expression, significantly inhibited cellular cholesterol accumulation, suppressed foam cell formation, improved mitochondrial function, attenuated oxidative stress, and alleviated NLRP3 activation in ox-LDL-stimulated macrophages. Moreover, above protective effects of DMY was unavailable in macrophages from SIRT3 KO mice. Collectively, the study demonstrated the protective role of SIRT3 against oxidative stress and NLRP3 inflammasome in cholesterol accumulation and foam cell formation of macrophages with ox-LDL-stimulation, which is beneficial to provide novel strategy for atherosclerosis prevention and treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bcp.2021.114665DOI Listing
June 2021

Molecular and MALDI-ToF MS differentiation and antifungal susceptibility of prevalent clinical Fusarium species in China.

Mycoses 2021 Jun 26. Epub 2021 Jun 26.

Department of Dermatology and Venerology, Peking University First Hospital, Beijing, China.

Background: Fusarium species are emerging causative agents of superficial and disseminated human infections. Early diagnosis and treatment contribute to better prognosis of severe infection.

Objectives: To detect the effectiveness of matrix-assisted laser desorption ionisation time of flight mass spectrometry (MALDI-ToF MS) for Fusarium identification, and evaluate the susceptibility profiles to clinical available antifungals.

Methods: All 203 clinical Fusarium isolates and 25 environmental isolates were identified by using translation elongation factor 1-alpha (TEF1) and RNA polymerase subunit II (RPB2) sequencing and MALDI-ToF MS. Antifungal susceptibility testing was determined by a microdilution method following the CLSI approved standard M38-A3 document.

Results: Correct identification rates at the species and genus levels were 89.04% (203/228) and 95.18% (217/228), respectively, using Bruker Filamentous Fungi Library 1.0 combined with the novel database. Seven species complexes with 19 Fusarium species were identified, including F. solani (59.21%, n = 135), F. verticillioides (17.54%, n = 40), F. proliferatum (6.58%, n = 15) and F. oxysporum (4.39%, n = 10). Four uncommon species complexes (F. incarnatum-equiseti SC, F. dimerum SC, F. redolens SC and F. sporotrichioides SC) were also identified. A high degree of antifungal resistance was observed. Fusarium isolates exhibited lower MICs to luliconazole and terbinafine compared with amphotericin B and voriconazole, which in turn were significantly more active than amorolfine, fluconazole and itraconazole.

Conclusions: MALDI-ToF MS showed good performance in Fusarium species with an adapted Bruker library and expanded database. Fusarium isolates exhibited lower MICs to luliconazole and terbinafine compared to amphotericin B and voriconazole.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/myc.13345DOI Listing
June 2021

Therapeutic and Improving Function of Lactobacilli in the Prevention and Treatment of Cardiovascular-Related Diseases: A Novel Perspective From Gut Microbiota.

Front Nutr 2021 7;8:693412. Epub 2021 Jun 7.

Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

The occurrence and development of cardiovascular-related diseases are associated with structural and functional changes in gut microbiota (GM). The accumulation of beneficial gut commensals contributes to the improvement of cardiovascular-related diseases. The cardiovascular-related diseases that can be relieved by supplementation, including hypercholesterolemia, atherosclerosis, myocardial infarction, heart failure, type 2 diabetes mellitus, and obesity, have expanded. As probiotics, lactobacilli occupy a substantial part of the GM and play important functional roles through various GM-derived metabolites. Lactobacilli ultimately have a beneficial impact on lipid metabolism, inflammatory factors, and oxidative stress to relieve the symptoms of cardiovascular-related diseases. However, the axis and cellular process of gut commensal in improving cardiovascular-related diseases have not been fully elucidated. Additionally, strains produce diverse antimicrobial peptides, which help maintain intestinal homeostasis and ameliorate cardiovascular-related diseases. These strains are a field that needs to be further investigated immediately. Thus, this review demonstrated the mechanisms and summarized the evidence of the benefit of strain supplementation from animal studies and human clinical trials. We also highlighted a broad range of lactobacilli candidates with therapeutic capability by mining their metabolites. Our study provides instruction in the development of lactobacilli as a functional food to improve cardiovascular-related diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnut.2021.693412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215129PMC
June 2021

Topological kink states in graphene.

Nanotechnology 2021 Jul 12;32(40). Epub 2021 Jul 12.

School of Physical Science and Technology, Soochow University, Suzhou 215006, People's Republic of China.

Due to the unique band structure, graphene exhibits a number of exotic electronic properties that have not been observed in other materials. Among them, it has been demonstrated that there exist the one-dimensional valley-polarized topological kink states localized in the vicinity of the domain wall of graphene systems, where a bulk energy gap opens due to the inversion symmetry breaking. Notably, the valley-momentum locking nature makes the topological kink states attractive to the property manipulation in valleytronics. This paper systematically reviews both the theoretical research and experimental progress on topological kink states in monolayer graphene, bilayer graphene and graphene-like classical wave systems. Besides, various applications of topological kink states, including the valley filter, current partition, current manipulation, Majorana zero modes and etc, are also introduced.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1088/1361-6528/ac0dd8DOI Listing
July 2021

New genetic variants associated with major adverse cardiovascular events in patients with acute coronary syndromes and treated with clopidogrel and aspirin.

Pharmacogenomics J 2021 Jun 22. Epub 2021 Jun 22.

Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Although a few studies have reported the effects of several polymorphisms on major adverse cardiovascular events (MACE) in patients with acute coronary syndromes (ACS) and those undergoing percutaneous coronary intervention (PCI), these genotypes account for only a small fraction of the variation and evidence is insufficient. This study aims to identify new genetic variants associated with MACE end point during the 18-month follow-up period by a two-stage large-scale sequencing data, including high-depth whole exome sequencing of 168 patients in the discovery cohort and high-depth targeted sequencing of 1793 patients in the replication cohort. We discovered eight new genotypes and their genes associated with MACE in patients with ACS, including MYOM2 (rs17064642), WDR24 (rs11640115), NECAB1 (rs74569896), EFR3A (rs4736529), AGAP3 (rs75750968), ZDHHC3 (rs3749187), ECHS1 (rs140410716), and KRTAP10-4 (rs201441480). Notably, the expressions of MYOM2 and ECHS1 are downregulated in both animal models and patients with phenotypes related to MACE. Importantly, we developed the first superior classifier for predicting 18-month MACE and achieved high predictive performance (AUC ranged between 0.92 and 0.94 for three machine-learning methods). Our findings shed light on the pathogenesis of cardiovascular outcomes and may help the clinician to make a decision on the therapeutic intervention for ACS patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41397-021-00245-5DOI Listing
June 2021

A cryoprotectant supplemented with pentoxifylline can improve the effect of freezing on the motility of human testicular sperm.

Zygote 2021 Jun 22:1-6. Epub 2021 Jun 22.

Andrology/Human Sperm Bank, West China Second University Hospital, Sichuan University, Chengdu610041, China.

This study examined the effect of a cryoprotectant with and without pentoxifylline supplementation on the motility and viability of human testicular sperm, both before and after freezing. Testicular samples were obtained from 68 patients with azoospermia who came to the Andrology Service of West China Second University Hospital, Sichuan University, for testicular biopsies from December 2019 to April 2020. All patients were assigned randomly to two groups: experimental, whose testicular sperm were added to the cryoprotectant with pentoxifylline, and the control, whose testicular sperm were added to the cryoprotectant without pentoxifylline. Both groups used the same freezing and thawing methods. Testicular sperm motility in the experimental group was significantly higher than that of the control group, both before and after cryopreservation. The recovery rate of sperm motility in the experimental group was significantly higher than that of the control group. The percentage of samples with motile testicular sperm in the experimental group was significantly higher than that of the control group after thawing. Sperm viability was unchanged between the experimental and control groups, both before and after freezing. Overall, a pentoxifylline-supplemented cryoprotectant can significantly improve the motility of testicular sperm before and after cryopreservation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S0967199421000368DOI Listing
June 2021

Cytomegalovirus Latency Exacerbated small-for-size Liver Graft Injury through Activation of CCL19/CCR7 in Hepatic Stellate Cells.

Transplantation 2021 Jun 2. Epub 2021 Jun 2.

1Department of Surgery, HKU-SZH & Faculty of Medicine, The University of Hong Kong, Hong Kong, China 2AIDS Institute and Department of Microbiology, Faculty of Medicine, The University of Hong Kong, Hong Kong, China 3Institute of Immunology, School of Medicine, Zhejiang Univerisity, Hangzhou, Zhejiang, China.

Background: The interplay between cytomegalovirus (CMV) latency and graft malfunction after living donor liver transplantation (LDLT) remains poorly defined due to the complexity of clinical confounding factors. Here, we aimed to investigate the effects of CMV latency on small-for-size graft injury and to get further insight on the pathogenic role of hepatic stellate cells (HSCs) in this process.

Methods: Rat orthotopic liver transplantation with small-for-size grafts was performed in a CMV latent model developed in immunocompetent Sprague Dawley (SD) rats using Priscott strain. Post-transplant graft injury including hepatocyte damage, stellate cell activation and fibrogenesis were evaluated. Differential gene expression of HSCs in response to CMV latency was screened by cDNA microarray. Clinical validation was further conducted in human biopsies.

Results: CMV latency aggravated hepatocyte apoptosis/necrosis in the early phase, enhanced HSC expansion and graft fibrosis during the middle-late phase in small-for-size liver grafts of the rat model. cDNA microarray mining revealed CCL19/CCR7 as one of the most noteworthy pathways bridging HSC activation and liver graft injury in the presence of CMV latency. Together with CCL19 upregulation, coherent overexpression of CCR7 in accumulated HSCs was confirmed in both rat and human CMV latent recipients. Moreover, addition of CCL19 in vitro promoted HSC migration by increasing the level of matrix metalloproteinase-2 (MMP2).

Conclusion: Our data demonstrated that CMV latency aggravated early/late phase liver graft damage and fibrogenesis via CCL19/CCR7/HSCs axis. Blockade of CMV latency-related stellate cell activation may shed light on the strategy of graft protection clinically.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000003846DOI Listing
June 2021

Pan-Cancer Prognostic, Immunity, Stemness, and Anticancer Drug Sensitivity Characterization of N6-Methyladenosine RNA Modification Regulators in Human Cancers.

Front Mol Biosci 2021 4;8:644620. Epub 2021 Jun 4.

Department of Pulmonary and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China.

N6-methyladenosine RNA modification plays a significant role in the progression of multiple tumorigenesis. Our study identified the imperative role of m6A regulators in the tumor immune microenvironment, survival, stemness score, and anticancer drug sensitivity of pan-cancer. The Wilcox test was to identify the differential expression between 17 m6A regulators across 33 TCGA cancer types and their normal tissues from UCSC Xena GDC pan-cancer. Survival analysis of m6A-related regulators in 33 TCGA cancer types was identified using the "survival" and "survminer" package. The Spearman correlation test and Pearson correlation test were used to identify the correlation relationship between m6A regulators expression and tumor microenvironment, tumor stem cell score, and drug sensitivity of anticancer drugs. ConsensusPathDB was used for exploring m6A regulators functional enrichment. The 17 (METTL3, WTAP, METTL14, RBM15, RBM15B, VIRMA, HNRNPC, HNRNPA2B1, YTHDC1, ZC3H13, YTHDF1, YTHDC2, YTHDF2, IGF2BP3, IGF2BP1, FTO, and ALKBH5) m6A regulators were differentially expressed in 18 TCGA cancer types and adjacent normal tissues. Correlation analysis indicated that the relationship between the expression of 17 m6A regulators and tumor microenvironment indicated that the higher expression of m6A regulators, the higher the degree of tumor stem cells. The anticancer drug sensitivity analysis indicated that ZC3H13 expression had a positive relationship with anticancer drugs such as selumetinib, dabrafenib, cobimetinib, trametinib, and hypothemycin ( < 0.001). YTHDF2 expression was significantly negatively correlated with the anticancer drug dasatinib ( < 0.001). The pan-cancer immune subtype analysis showed that the 17 m6A regulators were significantly different in immune subtype C1 (wound healing), C3 (inflammatory), C2 (IFN-gamma dominant), C5 (immunological quiet), C4 (lymphocyte depleted), and C6 (TGF-beta dominant) ( < 0.001). Our study provides a comprehensive insight for revealing the significant role of m6A regulators in the tumor immune microenvironment, stemness score, and anticancer drug sensitivity of human cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmolb.2021.644620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211991PMC
June 2021

Identification of 3, 4-disubstituted pyridine derivatives as novel CDK8 inhibitors.

Eur J Med Chem 2021 Jun 11;223:113634. Epub 2021 Jun 11.

Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. Electronic address:

Selective inhibition of cyclin-dependent kinase 8 (CDK8) has been recently regarded as a potential approach for cancer therapy. A series of novel CDK8 inhibitors with the pyridine core was identified via scaffold hopping from the known CDK8 inhibitor A-7. The new inhibitors were designed to improve the ligand efficiency so as to enhance drug-likeness. Most of the compounds showed significant inhibition against CDK8/cyclin C, and the most active compounds (5d, 5e and 7') displayed IC values of 2.4 nM, 5.0 nM and 7.7 nM, respectively. Preliminary kinase profiling of selected compounds against a panel of kinases from different families indicated that this compound class might selectively inhibit CDK8 as well as its paralog CDK19. Some compounds exhibited cellular activity in both MTT and SRB assays against a variety of tumor cells, including HCT-116, A549, MDA-MB-231, KB, KB-VIN and MCF-7. Further flow cytometry analysis revealed a dose-dependent G2/M phase arrest in MDA-MB-231 cells treated with compounds 6'a, 6'b, 6'j and 6'k. In addition, compound 6'k demonstrated moderate antitumor efficacy in HCT-116 mouse models, although unfavorable pharmacokinetic profiles were suggested by preliminary study in mice. The results provided a new structural prototype for the search of selective CDK8 inhibitors as antitumor agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmech.2021.113634DOI Listing
June 2021

The pan-cancer lncRNA PLANE regulates an alternative splicing program to promote cancer pathogenesis.

Nat Commun 2021 06 18;12(1):3734. Epub 2021 Jun 18.

Translational Research Institute, Henan Provincial People's Hospital and People's Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University, Henan, China.

Genomic amplification of the distal portion of chromosome 3q, which encodes a number of oncogenic proteins, is one of the most frequent chromosomal abnormalities in malignancy. Here we functionally characterise a non-protein product of the 3q region, the long noncoding RNA (lncRNA) PLANE, which is upregulated in diverse cancer types through copy number gain as well as E2F1-mediated transcriptional activation. PLANE forms an RNA-RNA duplex with the nuclear receptor co-repressor 2 (NCOR2) pre-mRNA at intron 45, binds to heterogeneous ribonucleoprotein M (hnRNPM) and facilitates the association of hnRNPM with the intron, thus leading to repression of the alternative splicing (AS) event generating NCOR2-202, a major protein-coding NCOR2 AS variant. This is, at least in part, responsible for PLANE-mediated promotion of cancer cell proliferation and tumorigenicity. These results uncover the function and regulation of PLANE and suggest that PLANE may constitute a therapeutic target in the pan-cancer context.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-24099-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213729PMC
June 2021

Disseminated trichosporosis in a young patient with CARD9 deficiency.

Clin Microbiol Infect 2021 Jun 16. Epub 2021 Jun 16.

Department of Dermatology, Peking University First Hospital, Research Center for Medical Mycology, Peking University, National Clinical Research Center for Skin and Immune Diseases, Beijing, China. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cmi.2021.06.012DOI Listing
June 2021