Publications by authors named "Shuai Zhao"

386 Publications

Nimodipine reduces delayed cerebral vasospasm after intracranial tumor surgery: A Retrospective Study.

Clin Exp Pharmacol Physiol 2021 Aug 3. Epub 2021 Aug 3.

Department of Neurosurgery, First Hospital of Jilin University, Changchun, Jilin, 130021, China.

Cerebral vasospasm (CVS) is a frequent and serious neurosurgical complication, without sufficient therapy. This retrospective study was performed to analyze if nimodipine can improve prognosis and reduces ischemia secondary to delayed CVS after intracranial tumor surgery. A retrospective review was performed over the years 2011 to 2012 for patients with an anterior cranial fossa tumor and underwent intracranial tumor surgery. And the surgical field was soaked with nimodipine solution or normal saline. Transcranial Doppler ultrasonography was used to measure velocity in the middle cerebral artery (MCA) and the distal extracranial internal carotid artery (eICA). Follow-up was performed using the Glasgow Outcome Scale (GOS) after discharge. 94 patients that met the inclusion criteria. They included 50 males and 44 females, with a mean age of 49.6 yr. In the nimodipine group, CVS occurred in 13 patients; 9 patients had CVS between 4 and 7 days, and 4 had CVS between 8 and 14 days. In the normal saline group, 19 patients had CVS, 3 presented with CVS within 3 days, 11 between 4-7 days and 5 between 8-14 days. A significant difference in the occurrence of CVS was observed between the two groups. Preoperative and postoperative the MCA velocities were compared, revealing a significant change in the normal saline group but not in the nimodipine group. Nimodipine markedly improves prognosis and significantly reduces ischemia secondary to delayed CVS after intracranial tumor surgery, as well as the risks of mortality and morbidity.
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http://dx.doi.org/10.1111/1440-1681.13564DOI Listing
August 2021

Thoracic full-endoscopic unilateral laminotomy with bilateral decompression for treating ossification of the ligamentum flavum with myelopathy.

Ann Transl Med 2021 Jun;9(12):977

Guangzhou University of Chinese Medicine, Guangzhou, China.

Background: The aim of the present study was to evaluate the curative effect and safety of thoracic full-endoscopic unilateral laminotomy with bilateral decompression (TE-ULBD) for treating ossification of the ligamentum flavum (OLF) with myelopathy.

Methods: Between January 2015 and December 2018, 23 consecutive patients with symptomatic thoracic OLF were treated with TE-ULBD. Of these, 21 (13 women and 8 men, aged 49-75 years) were included in the study and followed up for a minimum of 1 year. The mean blood loss was 15.48 mL (10-30 mL), operative duration was 78.86 min (55-115 min), and hospitalization was 5.05 days (3-15 days). The Japanese Orthopaedic Association (JOA) was used to evaluate spinal cord function, and the curative effect was defined by the JOA improvement rate. The area of OLF (AOLF), the maximum spinal cord compression (MSCC), and the area of spinal cord (ASC) were used to evaluate OLF clearance and spinal cord decompression status.

Results: At the final follow up,the JOA score was 8.33 points (5-11 points), which was a significant improvement from the preoperative 5.33 points (3-9 points, P<0.01). The excellent and good rate was 76.19% (16/21). The average preoperative AOLF and AOLF ratio were 85.27±23.66 mm and 57.86%±11.86%, respectively, and the postoperative AOLF and AOLF ratio were 16.27±11.75 mm and 8.13%±5.38%, respectively. The MSCC increased from 27.99%±13.51% preoperatively to 48.02%±6.66% postoperatively. The ASC was 42.90±10.60 mm preoperatively and 64.54±21.36 mm postoperatively. There were statistically significant differences in all parameters preoperatively and postoperatively (P<0.01). One case had postoperative hematoma, and the symptoms gradually eased after 3 weeks of conservative treatment. There were no other complications. No recurrence of OLF was detected during the follow-up period.

Conclusions: TE-ULBD is safe and effective for thoracic OLF with the advantages of reduced trauma and bleeding, and faster recovery.
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http://dx.doi.org/10.21037/atm-21-2181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267270PMC
June 2021

Prognosis and Biological Behavior of Gastric Signet-Ring Cell Carcinoma Better or Worse: A Meta-Analysis.

Front Oncol 2021 30;11:603070. Epub 2021 Jun 30.

Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, China.

Background: The clinical pathology of gastric signet-ring cell carcinoma (SRC) is still unclear. This meta-analysis was performed to evaluate the difference in biological behavior and prognosis between SRC and non-signet ring cell carcinoma (NSRC).

Methods: A total of 58 eligible studies were analyzed using RevMan and other auxiliary software. Biological behaviors were compared based on odds ratio (OR) and mean difference (MD). Hazards ratio (HR) was calculated for prognosis based on Kaplan-Meier curves.

Results: Totally, 28,946 SRC patients were compared with 81,917 NSRC patients. Compared with NSRC patients, lower male: female ratio (OR = 0.53, < 0.01), younger age (MD = -4.89, < 0.01), more middle location (OR = 1.64, < 0.01), more depressed type at early stage (OR = 1.31, < 0.05), higher incidence of Borrmann type IV (OR = 1.96, < 0.01), less lymph node metastasis at early stage (OR = 0.78, < 0.05), better prognosis at early stage (HR = 0.59, < 0.01), and worse prognosis at advanced stage (HR = 1.19, < 0.01) were associated with SRC patients.

Conclusion: The prognosis of SRC at early stage is better than other types of gastric cancer, while that of SRC at advanced stage is relatively poorer.
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http://dx.doi.org/10.3389/fonc.2021.603070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278333PMC
June 2021

A Prognostic Autophagy-Related Long Non-coding RNA (ARlncRNA) Signature in Acute Myeloid Leukemia (AML).

Front Genet 2021 30;12:681867. Epub 2021 Jun 30.

Department of Hematology, Shangrao People's Hospital, Shangrao, China.

Background: Some studies have proven that autophagy and lncRNA play important roles in AML. Several autophagy related lncRNA signatures have been shown to affect the survival of patients in some other cancers. However, the role of autophagy related lncRNA in AML has not been explored yet. Hence, this study aims to find an autophagy related lncRNA signature that can affect survival for AML patients.

Method: A Pearson correlation analysis, a Kaplan-Meier survival curve, a univariate cox regression, and a multivariate cox regression were performed to establish an autophagy related lncRNA signature. A univariate cox regression, a multivariate cox regression, a Kaplan-Meier survival curve, and a ROC curve were applied to confirm if the signature is an independent prognosis for AML patients. The relationship between the signature and the clinical features was explored by using a test. Gene Set Enrichment Analysis (GSEA) was used to investigate the potential tumor related pathways.

Results: A four-autophagy related lncRNA (MIR133A1HG, AL359715.1, MIRLET7BHG, and AL356752.1) signature was established. The high risk score based on signature was related to the short survival time of AML patients. The signature was an independent factor for the prognosis for AML patients (HR = 1.684, 95% CI = 1.324-2.142, < 0.001). The signature was correlated with age, leukocyte numbers, and FAB (M3 or non-M3). The P53, IL6/JAK/STAT3, TNF-α, INF-γ, and IL2/STAT5 pathways might contribute to the differences between the risk groups based on signature in AML.

Conclusion: The four autophagy related lncRNAs and their signature might be novel biomarkers for predicting the survival of AML patients. Some biological pathways might be the potential mechanisms of the signature for the survival of AML patients.
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http://dx.doi.org/10.3389/fgene.2021.681867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278057PMC
June 2021

Optics metrology and at-wavelength wavefront characterization by a microfocus X-ray grating interferometer.

Opt Express 2021 Jul;29(14):22704-22713

A microfocus X-ray grating interferometer (MFXGI) is proposed to measure the profile of the X-ray wavefront and slope error of X-ray optical elements. This device consists of a phase grating G to modulate the incoming wavefront and an absorption grating G as a transmission mask for the position-sensitive detector. The wavefront distortions caused by the deformable mirror were analyzed under operating conditions for in situ investigation of X-ray optical elements. The MFXGI can obtain direct and reflected beams in one recorded image at the same time through a microfocus X-ray source. The direct beam can be used to calculate the parameter errors and spherical shape for error compensation and retrieve the aspherical shape of the height profile. This instrument is expected to be a valuable tool for further technical progress in X-ray adaptive optics and X-ray mirror manufacturing and mounting.
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http://dx.doi.org/10.1364/OE.430269DOI Listing
July 2021

Predictive Score of Risk Associated with Progression of Patients with COVID-19 Pneumonia in Wuhan, China: the ALA Score.

Arab J Sci Eng 2021 Jun 28:1-9. Epub 2021 Jun 28.

Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Harbin Medical University, Harbin, 150081 China.

The Coronavirus Disease 2019 (COVID-19) had become a Public Health Emergency of International Concern with more than 90 million confirmed cases worldwide. Therefore, this study aims to establish a predictive score model of progression to severe type in patients with COVID-19. This is a retrospective cohort study of 151 patients with COVID-19 diagnosed by nucleic acid test or specific serum antibodies from February 13, 2020, to March 14, 2020, hospitalized in a COVID-19-designed hospital in Wuhan, China. Of the 151 patients with average age of 63 years, 64 patients were male (42.4%), and 29 patients (19.2%) were classified as severe group. Multivariate analysis showed that age > 65 years (odds ratio [OR] = 9.72, 95%CI: 2.92-32.31,  < 0.001), lymphocyte count ≤ 1.1 × 10/L (OR = 3.42, 95%CI: 1.24-9.41,  = 0.017) and AST > 35 U/L (OR = 3.19, 95%CI: 1.11-9.19,  = 0.032) were independent risk factors for the disease severity. The area under curve (AUC) of receiver operating characteristic curve of the probabilities of the composite continuous variable (age + lymphocyte + AST) is 0.796. Finally, a predictive score model called ALA was established, and its AUC was 0.83 (95%CI: 0.75-0.92). Using a cutoff value of 9.5 points, the positive and negative predictive values were 54.1% (38-70.1%) and 92.1% (87.2-97.1%), respectively. The ALA score model can quickly identify severe patients with COVID-19, so as to help clinicians to better choose accurate management strategy.
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http://dx.doi.org/10.1007/s13369-021-05808-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237254PMC
June 2021

Macrocyclic Photoinitiator Based on Prism[5]arene Matching LEDs Light with Low Migration.

Macromol Rapid Commun 2021 Jun 25:e2100299. Epub 2021 Jun 25.

State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, Changzhou Institute of Advanced Materials, Beijing University of Chemical Technology, Beijing, 100029, P. R. China.

In this work, a naphthalene-based macrocycle prism[5]arene (NP OCH ) is developed as a novel kind of photoinitiator. When NP OCH is irradiated under light, the bond between methylene and naphthalene can be quickly broken owning to the existence of ring tension. The macrocycle is cleaved to linear oligomer biradicals, which can effectively initiate the free radical photopolymerization of acrylate monomers. Compared with conventional photoinitiators, NP OCH has strong light absorption in the wavelength range of 365-405 nm, so it can well match the environment-friendly light-emitting diodes (LEDs) light source to realize highly efficient initiation. In addition, there is no small molecule fragment generated during NP OCH fracture, and the resulted linear oligomer biradicals can be immobilized in the polymer after initiating polymerization, so NP OCH photoinitiators show much lower migration rate and cytotoxicity. Cleavable macrocycle prismarene may provide a new idea for the design of safe and efficient photoinitiators matching long wavelength light.
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http://dx.doi.org/10.1002/marc.202100299DOI Listing
June 2021

Phase separation drives aberrant chromatin looping and cancer development.

Nature 2021 Jul 23;595(7868):591-595. Epub 2021 Jun 23.

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.

The development of cancer is intimately associated with genetic abnormalities that target proteins with intrinsically disordered regions (IDRs). In human haematological malignancies, recurrent chromosomal translocation of nucleoporin (NUP98 or NUP214) generates an aberrant chimera that invariably retains the nucleoporin IDR-tandemly dispersed repeats of phenylalanine and glycine residues. However, how unstructured IDRs contribute to oncogenesis remains unclear. Here we show that IDRs contained within NUP98-HOXA9, a homeodomain-containing transcription factor chimera recurrently detected in leukaemias, are essential for establishing liquid-liquid phase separation (LLPS) puncta of chimera and for inducing leukaemic transformation. Notably, LLPS of NUP98-HOXA9 not only promotes chromatin occupancy of chimera transcription factors, but also is required for the formation of a broad 'super-enhancer'-like binding pattern typically seen at leukaemogenic genes, which potentiates transcriptional activation. An artificial HOX chimera, created by replacing the phenylalanine and glycine repeats of NUP98 with an unrelated LLPS-forming IDR of the FUS protein, had similar enhancing effects on the genome-wide binding and target gene activation of the chimera. Deeply sequenced Hi-C revealed that phase-separated NUP98-HOXA9 induces CTCF-independent chromatin loops that are enriched at proto-oncogenes. Together, this report describes a proof-of-principle example in which cancer acquires mutation to establish oncogenic transcription factor condensates via phase separation, which simultaneously enhances their genomic targeting and induces organization of aberrant three-dimensional chromatin structure during tumourous transformation. As LLPS-competent molecules are frequently implicated in diseases, this mechanism can potentially be generalized to many malignant and pathological settings.
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http://dx.doi.org/10.1038/s41586-021-03662-5DOI Listing
July 2021

miR-483-3p Promotes IL-33 Production from Fibroblast-Like Synoviocytes by Regulating ERK Signaling in Rheumatoid Arthritis.

Inflammation 2021 Jun 23. Epub 2021 Jun 23.

Department of Rheumatology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.

Our previous studies have identified miR-483-3p to be highly expressed in synoviocytes from patients with rheumatoid arhtirits (RA); however, its effects on inflammation of RA fibroblast-like synoviocytes (FLSs) have remained unclear. The expression of miR-483-3p and cytokines in RA FLSs was detected using quantitative real-time polymerase chain reaction. Enzyme-linked immunosorbent was conducted to determine interleukin (IL)-33 production from RA FLSs. Western blotting was employed to quantify the levels of p-ERK and total ERK. Overexpressed miR-483-3p significantly increased the mRNA and protein expression of IL-33, but not of IL-27 or IL-34, in RA FLSs, whereas miR-483-3p suppression showed the opposite effects. Furthermore, miR-483-3p upregulation activated the ERK signaling pathway. The ERK signaling inhibitor PD98059 partly reversed the elevation of IL-33 levels mediated by miR-483-3p overexpression. Our results reveal that miR-483-3p promotes IL-33 expression by regulating the ERK signaling pathway in RA FLSs. Thus, miR-483-3p may be a potential effective target for RA treatment.
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http://dx.doi.org/10.1007/s10753-021-01503-1DOI Listing
June 2021

Comparison of intracorporeal and extracorporeal anastomosis and resection in right colectomy: a systematic review and meta-analysis.

Langenbecks Arch Surg 2021 Jun 21. Epub 2021 Jun 21.

Department of Emergency, The Second Hospital of Jiaxing, Jiaxing, 314000, Zhejiang Province, China.

Purpose: Laparoscopic surgery is the standard surgical approach for colon cancer. However, there is no standard surgery for right colectomy. Selection between total laparoscopic right colectomy (TLRC) and laparoscopic-assisted right colectomy (LARC) is a topic of interest. In this systematic review, we compared the short-term outcomes of TLRC and LARC in the treatment of right colon cancer.

Methods: We identified studies (PubMed, Web of Science, Cochrane Library, Embase) comparing TLRC and LARC up to February 2021. Surgical duration; volume of intraoperative blood loss; number of harvested lymph nodes; incision length; hospitalization duration; time to first flatus; time to first defecation; and anastomotic leakage, ileus, and wound infection were compared.

Results: Thirty studies (TLRC, 1948 patients; LARC, 2369 patients) were evaluated. All studies were retrospective, except seven prospective studies, three RCTs, and three case-control studies. TLRC demonstrated lesser intraoperative blood loss volume (P < 0.01), less frequent intraoperative conversion to laparotomy (P = 0.02), shorter hospitalization duration (P < 0.01), smaller incision length (P < 0.01), shorter time to first flatus (P < 0.01) and first defecation (P < 0.01), and lesser frequent wound infection (P < 0.01) compared with LARC. The surgical duration, number of harvested lymph nodes, anastomotic leakage, and ileus were similar between TLRC and LARC (P > 0.05).

Conclusion: TLRC is associated with significantly earlier bowel recovery, lesser blood loss, smaller incision length, lower rate of conversion, shorter hospitalization duration, and lesser frequent wound infection compared with LARC.
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http://dx.doi.org/10.1007/s00423-021-02235-4DOI Listing
June 2021

Improvement of cellulase and xylanase production in Penicillium oxalicum under solid-state fermentation by flippase recombination enzyme/ recognition target-mediated genetic engineering of transcription repressors.

Bioresour Technol 2021 Oct 2;337:125366. Epub 2021 Jun 2.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Guangxi Research Center for Microbial and Enzyme Engineering Technology, College of Life Science and Technology, Guangxi University, Nanning, China. Electronic address:

Penicillium oxalicum has received increasing attention as a potential cellulase-producer. In this study, a copper-controlled flippase recombination enzyme/recognition target (FLP/FRT)-mediated recombination system was constructed in P. oxalicum, to overcome limited availability of antibiotic resistance markers. Using this system, two crucial transcription repressor genes atf1 and cxrC for the production of cellulase and xylanase under solid-state fermentation (SSF) were simultaneously deleted, thereby leading to 2.4- to 29.1-fold higher cellulase and 78.9% to 130.8% higher xylanase production than the parental strain under SSF, respectively. Glucose and xylose released from hydrolysis of pretreated sugarcane bagasse achieved 10.6%-13.5% improvement by using the crude enzymes from the engineered strain Δatf1ΔcxrC::flp under SSF in comparison with that of the parental strain. Consequently, these results provide a feasible strategy for improved cellulase and xylanase production by filamentous fungi.
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http://dx.doi.org/10.1016/j.biortech.2021.125366DOI Listing
October 2021

Dispersal and mating patterns determine the fate of naturally dispersed populations: evidence from Bombina orientalis.

BMC Ecol Evol 2021 06 7;21(1):111. Epub 2021 Jun 7.

College of Life Science, Northeast Agricultural University, No. 600 Changjiang Road Xiangfang District, Harbin, 150030, China.

Background: In contrast to the explosive increase of a population following biological invasion, natural dispersal, i.e., when a population disperses from its original range into a new range, is a passive process that is affected by resources, the environment, and other factors. Natural dispersal is also negatively impacted by genetic drift and the founder effect. Although the fates of naturally dispersed populations are unknown, they can adapt evolutionarily over time to the new environment. Can naturally dispersed populations evolve beneficial adaptive strategies to offset these negative effects to maintain their population in a stable state?

Results: The current study addressed this question by focusing on the toad Bombina orientalis, the population of which underwent natural dispersal following the Last Glacial Maximum in Northeast Asia. Population genetic approaches were used to determine the genetic structure, dispersal pattern, and mating system of the population of B. orientalis in northeast China (Northern population). The results showed that this northern population of B. orientalis is a typical naturally dispersed population, in which the stable genetic structure and high level of genetic diversity of the population have been maintained through the long-distance biased dispersal behavior of males and the pattern of promiscuity within the population.

Conclusions: Our findings suggest that naturally dispersed populations can evolve effective adaptive strategies to maintain a stable population. Different species may have different strategies. The relevance of these maintenance mechanisms for naturally dispersed populations provide a new perspective for further understanding the processes of speciation and evolution.
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http://dx.doi.org/10.1186/s12862-021-01844-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182911PMC
June 2021

A novel technology for separating live earthworm from vermicompost: Experiment, mechanism analysis, and simulation.

Waste Manag 2021 Jun 5;131:50-60. Epub 2021 Jun 5.

College of Engineering, Huazhong Agricultural University, Wuhan 430070, Hubei, China; Key Laboratory of Agricultural Equipment in Mid-lower Reaches of the Yangtze River, Ministry of Agriculture and Rural Affairs, Wuhan 430070, Hubei, China. Electronic address:

The vermicomposting is widely acknowledged as an effective and sustainable biological technology to dispose large scale organic solid waste such as livestock manure, crop residues and municipal sludge. The scale of vermicomposting has constantly increased over recent years due to high market demand for live earthworms. Rapid and efficient extraction and harvesting earthworm from large-scale vermicompost has become a bottle-neck problem at the end of vermicomposting. Currently, most earthworm separation is done manually or relies on simple tools, and is therefore low efficient, time consuming and labor intensive. In this study, to explore earthworm separation technology and underlying mechanisms, three major studies were conducted based on the developed separator: Earthworm separation experiment, mechanism analysis of separation, and separation process simulation. The result indicated that under a 45% moisture content of vermicompost, earthworm can be separated centrifugally with approximately 83.79% worm separation rate. The treatment capacity of separator is 21.2 kg of total vermicompost mixture per minute. The critical factor in earthworm-vermicompost separation is frictional force and liquid membrane adhesion at the contact interface of conical separator. The final separated X velocity of earthworms is higher, whereas the Y and Z velocities are less than those of vermicompost. The earthworms are centrifugally thrown to a specific area called the earthworm harvest position. The outcome of this study provides a valuable reference for improvement of earthworm harvest efficiency and for shortening the recycling period of vermicomposting products in practice.
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http://dx.doi.org/10.1016/j.wasman.2021.05.031DOI Listing
June 2021

Merging C(sp)-H activation with DNA-encoding.

Chem Sci 2020 Sep 7;11(45):12282-12288. Epub 2020 Sep 7.

Department of Chemistry, The Scripps Research Institute 10550 North Torrey Pines Road, La Jolla CA 92037 USA

DNA-encoded library (DEL) technology has the potential to dramatically expedite hit identification in drug discovery owing to its ability to perform protein affinity selection with millions or billions of molecules in a few experiments. To expand the molecular diversity of DEL, it is critical to develop different types of DNA-encoded transformations that produce billions of molecules with distinct molecular scaffolds. Sequential functionalization of multiple C-H bonds provides a unique avenue for creating diversity and complexity from simple starting materials. However, the use of water as solvent, the presence of DNA, and the extremely low concentration of DNA-encoded coupling partners (0.001 M) have hampered the development of DNA-encoded C(sp)-H activation reactions. Herein, we report the realization of palladium-catalyzed C(sp)-H arylation of aliphatic carboxylic acids, amides and ketones with DNA-encoded aryl iodides in water. Notably, the present method enables the use of alternative sets of monofunctional building blocks, providing a linchpin to facilitate further setup for DELs. Furthermore, the C-H arylation chemistry enabled the on-DNA synthesis of structurally-diverse scaffolds containing enriched C(sp) character, chiral centers, cyclopropane, cyclobutane, and heterocycles.
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http://dx.doi.org/10.1039/d0sc03935gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162953PMC
September 2020

Synthesis of carbon-supported sub-2 nanometer bimetallic catalysts by strong metal-sulfur interaction.

Chem Sci 2020 Jul 14;11(30):7933-7939. Epub 2020 Jul 14.

Hefei National Laboratory for Physical Sciences at the Microscale, Department of Chemistry, University of Science and Technology of China Hefei 230026 China

Small-sized bimetallic nanoparticles that integrate the advantages of efficient exposure of the active metal surface and optimal geometric/electronic effects are of immense interest in the field of catalysis, yet there are few universal strategies for synthesizing such unique structures. Here, we report a novel method to synthesize sub-2 nm bimetallic nanoparticles (Pt-Co, Rh-Co, and Ir-Co) on mesoporous sulfur-doped carbon (S-C) supports. The approach is based on the strong chemical interaction between metals and sulfur atoms that are doped in the carbon matrix, which suppresses the metal aggregation at high temperature and thus ensures the formation of small-sized and well alloyed bimetallic nanoparticles. We also demonstrate the enhanced catalytic performance of the small-sized bimetallic Pt-Co nanoparticle catalysts for the selective hydrogenation of nitroarenes.
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http://dx.doi.org/10.1039/d0sc02620dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163286PMC
July 2020

G protein γ subunit modulates expression of plant-biomass-degrading enzyme genes and mycelial-development-related genes in Penicillium oxalicum.

Appl Microbiol Biotechnol 2021 Jun 2;105(11):4675-4691. Epub 2021 Jun 2.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Guangxi Research Center for Microbial and Enzyme Engineering Technology, College of Life Science and Technology, Guangxi University, 100 Daxue Road, Nanning, Guangxi, 530004, People's Republic of China.

Heterotrimeric-G-protein-mediated signaling pathways modulate the expression of the essential genes in many fundamental cellular processes in fungi at the transcription level. However, these processes remain unclear in Penicillium oxalicum. In this study, we generated knockout and knockout-complemented strains of gng-1 (POX07071) encoding the Gγ protein and found that GNG-1 modulated the expression of genes encoding plant-biomass-degrading enzymes (PBDEs) and sporulation-related activators. Interestingly, GNG-1 affected expression of the cxrB that encodes a known transcription factor required for the expression of major cellulase and xylanase genes. Constitutive overexpression of cxrB in ∆gng-1 circumvented the dependence of PBDE production on GNG-1. Further evidence indicated that CxrB indirectly regulated the transcription levels of key amylase genes by controlling the expression of the regulatory gene amyR. These data extended the diversity of Gγ protein functions and provided new insight into the signal transduction and regulation of PBDE gene expression in filamentous fungi. KEY POINTS: • GNG-1 modulates the expression of PBDE genes and sporulation-related genes. • GNG-1 controls expression of the key regulatory gene cxrB. • Overexpression of cxrB circumvents dependence of PBDE production on GNG-1.
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http://dx.doi.org/10.1007/s00253-021-11370-3DOI Listing
June 2021

SARS-CoV-2 exacerbates proinflammatory responses in myeloid cells through C-type lectin receptors and Tweety family member 2.

Immunity 2021 06 9;54(6):1304-1319.e9. Epub 2021 May 9.

Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA.

Despite mounting evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) engagement with immune cells, most express little, if any, of the canonical receptor of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2). Here, using a myeloid cell receptor-focused ectopic expression screen, we identified several C-type lectins (DC-SIGN, L-SIGN, LSECtin, ASGR1, and CLEC10A) and Tweety family member 2 (TTYH2) as glycan-dependent binding partners of the SARS-CoV-2 spike. Except for TTYH2, these molecules primarily interacted with spike via regions outside of the receptor-binding domain. Single-cell RNA sequencing analysis of pulmonary cells from individuals with coronavirus disease 2019 (COVID-19) indicated predominant expression of these molecules on myeloid cells. Although these receptors do not support active replication of SARS-CoV-2, their engagement with the virus induced robust proinflammatory responses in myeloid cells that correlated with COVID-19 severity. We also generated a bispecific anti-spike nanobody that not only blocked ACE2-mediated infection but also the myeloid receptor-mediated proinflammatory responses. Our findings suggest that SARS-CoV-2-myeloid receptor interactions promote immune hyperactivation, which represents potential targets for COVID-19 therapy.
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http://dx.doi.org/10.1016/j.immuni.2021.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106883PMC
June 2021

The language of chromatin modification in human cancers.

Nat Rev Cancer 2021 Jul 17;21(7):413-430. Epub 2021 May 17.

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.

The genetic information of human cells is stored in the context of chromatin, which is subjected to DNA methylation and various histone modifications. Such a 'language' of chromatin modification constitutes a fundamental means of gene and (epi)genome regulation, underlying a myriad of cellular and developmental processes. In recent years, mounting evidence has demonstrated that miswriting, misreading or mis-erasing of the modification language embedded in chromatin represents a common, sometimes early and pivotal, event across a wide range of human cancers, contributing to oncogenesis through the induction of epigenetic, transcriptomic and phenotypic alterations. It is increasingly clear that cancer-related metabolic perturbations and oncohistone mutations also directly impact chromatin modification, thereby promoting cancerous transformation. Phase separation-based deregulation of chromatin modulators and chromatin structure is also emerging to be an important underpinning of tumorigenesis. Understanding the various molecular pathways that underscore a misregulated chromatin language in cancer, together with discovery and development of more effective drugs to target these chromatin-related vulnerabilities, will enhance treatment of human malignancies.
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http://dx.doi.org/10.1038/s41568-021-00357-xDOI Listing
July 2021

Evolutionary history of the oriental fire-bellied toad () in Northeast China.

Ecol Evol 2021 May 5;11(9):4232-4242. Epub 2021 Mar 5.

College of Life Science Northeast Agricultural University Harbin China.

The evolutionary history of a species is generally affected by the combination of geological events and climate fluctuations. By analyzing the population features, genetic structure and the effective population historical dynamics of existing species, the population evolutionary history can be reestablished. In recent years, geological evidence shows that the Yilan-Yitong fault zone located in Northeast Asia experienced strong and frequent geological changes in the late Quaternary period. Species population history has been shaped by the combination of the complex climatic conditions of the Quaternary and Pleistocene glacial interglacial cycles and palaeogeological events in Northeast Asia and it has become a research focus for evolutionary biology researchers. In this study, mitochondrial and microsatellite molecular markers were used to reveal the population features, genetic structure, and the effective population historical dynamics of the Oriental fire-bellied toad (). The results showed that the strong seismic activity of the Yilan-Yitong fault zone in the late Quaternary period was the main reason for the population differentiation of Oriental fire-bellied toad in northeast China. The Quaternary Pleistocene glacial interglacial cycles led to the significant bottleneck effect of the western population located in the Maoer mountain area. As a result, the western population has low genetic diversity. Recent gene flow between eastern and western populations and historical evidence of population expansion proved that the dispersal behavior of the western populations was the main cause of the low genetic diversity and mitochondrial and nuclear discordance. Human economic activity may be the mainly driving factor. These evidences showed that the comprehensive influence of geology, climate, human activities and other factors should be considered in the process of exploring the evolutionary history of species.
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http://dx.doi.org/10.1002/ece3.7318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093726PMC
May 2021

An acoustic field-based conformal transfection system for improving the gene delivery efficiency.

Biomater Sci 2021 Jun;9(11):4127-4138

CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.

Ultrasound-activated microbubble destruction is a promising platform for gene delivery due to the low toxicity, non-invasiveness, and high specificity. However, the gene transfection efficiency is still low, especially for suspension cells. It is desirable to develop a universal gene delivery tool that overcomes the drawbacks existing in ultrasound-mediated methods. Here, we present a three-dimensional acoustic field-based conformal transfection (AFCT) system by designing a Sono-hole that can fit the three-dimensional acoustic field to maximally utilize the acoustic energy from bubble cavitation, thus greatly promoting the gene delivery efficiency. Surprisingly, compared with the traditional two-dimensional transfection system, the gene transfection efficiency of the AFCT system increased by more than 3 times, achieving nearly 30%. The parameters including acoustic pressure, duration, duty cycle, DNA concentrations, and bubble kinds were optimized to obtain higher gene transfection. In conclusion, our study provides an effective ultrasound-based gene delivery approach for gene transfection, especially for suspension-cultured cells.
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http://dx.doi.org/10.1039/d1bm00251aDOI Listing
June 2021

Isoflurane Suppresses Hippocampal High-frequency Ripples by Differentially Modulating Pyramidal Neurons and Interneurons in Mice.

Anesthesiology 2021 07;135(1):122-135

Background: Isoflurane can induce anterograde amnesia. Hippocampal ripples are high-frequency oscillatory events occurring in the local field potentials of cornu ammonis 1 involved in memory processes. The authors hypothesized that isoflurane suppresses hippocampal ripples at a subanesthetic concentration by modulating the excitability of cornu ammonis 1 neurons.

Methods: The potencies of isoflurane for memory impairment and anesthesia were measured in mice. Hippocampal ripples were measured by placing recording electrodes in the cornu ammonis 1. Effects of isoflurane on the excitability of hippocampal pyramidal neurons and interneurons were measured. A simulation model of ripples based on the firing frequency of hippocampal cornu ammonis 1 neurons was used to validate the effects of isoflurane on neuronal excitability in vitro and on ripples in vivo.

Results: Isoflurane at 0.5%, which did not induce loss of righting reflex, impaired hippocampus-dependent fear memory by 97.4 ± 3.1% (mean ± SD; n = 14; P < 0.001). Isoflurane at 0.5% reduced ripple amplitude (38 ± 13 vs. 42 ± 13 μV; n = 9; P = 0.003), rate (462 ± 66 vs. 538 ± 81 spikes/min; n = 9; P = 0.002) and duration (36 ± 5 vs. 48 ± 9 ms; n = 9; P < 0.001) and increased the interarrival time (78 ± 7 vs. 69 ± 6 ms; n = 9; P < 0.001) and frequency (148.2 ± 3.9 vs. 145.0 ± 2.9 Hz; n = 9; P = 0.001). Isoflurane at the same concentration depressed action potential frequency in fast-spiking interneurons while slightly enhancing action potential frequency in cornu ammonis 1 pyramidal neurons. The simulated effects of isoflurane on hippocampal ripples were comparable to recordings in vivo.

Conclusions: The authors' results suggest that a subanesthetic concentration of isoflurane can suppress hippocampal ripples by differentially modulating the excitability of pyramidal neurons and interneurons, which may contribute to its amnestic action.

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http://dx.doi.org/10.1097/ALN.0000000000003803DOI Listing
July 2021

Rapid One-Step Detection of Viral Particles Using an Aptamer-Based Thermophoretic Assay.

J Am Chem Soc 2021 05 4;143(19):7261-7266. Epub 2021 May 4.

Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, The Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, Zhejiang 310018, China.

Rapid and sensitive identification of viral pathogens such as SARS-CoV-2 is a critical step to control the pandemic disease. Viral antigen detection can compete with gold-standard PCR-based nucleic acid diagnostics in terms of better reflection of viral infectivity and reduced risk of contamination from enzymatic amplification. Here, we report the development of a one-step thermophoretic assay using an aptamer and polyethylene glycol (PEG) for direct quantitative detection of viral particles. The assay relies on aptamer binding to the spike protein of SARS-CoV-2 and simultaneous accumulation of aptamer-bound viral particles in laser-induced gradients of temperature and PEG concentration. Using a pseudotyped lentivirus model, a limit of detection of ∼170 particles μL (26 fM of the spike protein) is achieved in 15 min without the need of any pretreatment. As a proof of concept, the one-step thermophoretic assay is used to detect synthetic samples by spiking viral particles into oropharyngeal swabs with an accuracy of 100%. The simplicity, speed, and cost-effectiveness of this thermophoretic assay may expand the diagnostic tools for viral pathogens.
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http://dx.doi.org/10.1021/jacs.1c02929DOI Listing
May 2021

Characterization of hemicellulose in Cassava (Manihot esculenta Crantz) stem during xylogenesis.

Carbohydr Polym 2021 Jul 7;264:118038. Epub 2021 Apr 7.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Guangzhou, 510642, China; Guangdong Key Laboratory for Innovative Development and Utilization of Forest Plant Germplasm, College of Forestry and Landscape Architectures, South China Agricultural University, Guangzhou, 510642, China; Guangdong Laboratory of Lingnan Modern Agriculture, Guangzhou, 510642, China. Electronic address:

Cassava is one of the three major potato crops due to the high starch content in its tubers. Unlike most current studies on the utilization of cassava tubers, our research is mainly focused on the stem of cassava plant. Through nuclear magnetic resonance (NMR), fourier transform infrared spectrometer (FTIR) and other methods, we found that cassava stalk hemicellulose consists of β-1,4 glycosidic bond-linked xylan backbone with a tetrasaccharide reducing end and decorated with methylated glucuronic acid, acetyl groups and a high degree of arabinose substitutions. Hemicellulose content gradually increased from the upper to the lower parts of the stem. The apical part of cassava stalk contained more branched and heterogeneous glycans than the middle and basal parts, and the molecular weight of hemicellulose increased from top to bottom. Our findings will be helpful in understanding of structural variations of cassava hemicellulose during xylogenesis, as well as in better utilization of cassava plant waste in industry.
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http://dx.doi.org/10.1016/j.carbpol.2021.118038DOI Listing
July 2021

Surface-Mediated Construction of an Ultrathin Free-Standing Covalent Organic Framework Membrane for Efficient Proton Conduction.

Angew Chem Int Ed Engl 2021 Jun 31;60(27):14875-14880. Epub 2021 May 31.

Faculty of Chemistry, Northeast Normal University, Changchun, 130024, P. R. China.

As a new class of crystalline porous organic materials, covalent organic frameworks (COFs) have attracted considerable attention for proton conduction owing to their regular channels and tailored functionality. However, most COFs are insoluble and unprocessable, which makes membrane preparation for practical use a challenge. In this study, we used surface-initiated condensation polymerization of a trialdehyde and a phenylenediamine for the synthesis of sulfonic COF (SCOF) coatings. The COF layer thickness could be finely tuned from 10 to 100 nm by controlling the polymerization time. Moreover, free-standing COF membranes were obtained by sacrificing the bridging layer without any decomposition of the COF structure. Benefiting from the abundant sulfonic acid groups in the COF channels, the proton conductivity of the SCOF membrane reached 0.54 S cm at 80 °C in pure water. To our knowledge, this is one of the highest values for a pristine COF membrane in the absence of additional additives.
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http://dx.doi.org/10.1002/anie.202104106DOI Listing
June 2021

Visible-Light-Mediated Cyclopropanation Reactions of 3-Diazooxindoles with Arenes.

J Org Chem 2021 May 19;86(10):7131-7140. Epub 2021 Apr 19.

School of Pharmacy, Changzhou University, Changzhou, Jiangsu 213164, China.

The cyclopropanation reaction of 3-diazooxindoles with arenes was first accomplished using visible-light irradiation. A series of spiro[norcaradiene-7,3'-indolin]-2'-ones were synthesized for the first time in high yields and with excellent diastereoselectivities. The synthetic usefulness of this catalyst-free photochemical methodology is illustrated by the further controllable rearrangement and epoxidation reactions.
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http://dx.doi.org/10.1021/acs.joc.1c00418DOI Listing
May 2021

MiR-137 promotes cell growth and inhibits extracellular matrix protein expression in HO-induced human trabecular meshwork cells by targeting Src.

Neurosci Lett 2021 06 15;755:135902. Epub 2021 Apr 15.

Department of Ophthalmology, Xi'an NO.1 Hospital, Xi'an, 710002, China. Electronic address:

Glaucoma is a progressive optic neuropathy in more than 25 % of cases in patients with permanent blindness. The microRNA is implicated in modulating the cellular function of the trabecular meshwork (TM). The aim of this study is to investigate the role of miR-137 in glaucoma and illustrate the potential molecular mechanisms. We show that miR-137 was down-regulated in HO-induced human trabecular meshwork cells (HTMCs), and overexpression of miR-137 attenuated HO-induced cell growth inhibition, apoptosis and elevated extracellular matrix (ECM) protein expression. In addition, miR-137 blocked the activation of YAP/TAZ by directly targeting src. Overexpression of src or activation of the YAP/TAZ pathway partly abrogated the effects of miR-137 on HO-induced cell viability and apoptosis and dampened the inhibition effect on ECM protein expression. In conclusion, miR-137 promotes cell growth and inhibits extracellular matrix protein expression in HO-induced human trabecular meshwork cells via the YAP/TAZ pathway by targeting src. Hence, miR-137 might be used as a novel therapeutic target to treat glaucoma.
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http://dx.doi.org/10.1016/j.neulet.2021.135902DOI Listing
June 2021

Distinct impaired patterns of intrinsic functional network centrality in patients with early- and late-onset Alzheimer's disease.

Brain Imaging Behav 2021 Apr 12. Epub 2021 Apr 12.

Department of Radiology, The 2nd Affiliated Hospital of Zhejiang University School of Medicine, No.88 Jie-fang Road, Shang-cheng District, Hangzhou, 310009, China.

Early-onset Alzheimer's disease (EOAD) involves multiple cognitive domains and shows more rapid progression than late-onset Alzheimer's disease (LOAD). However, the difference in pathogenesis between EOAD and LOAD is still unclear. Accordingly, we applied intrinsic network analysis to explore the potential neuropathological mechanism underlying distinct clinical phenotypes. According to the cut-off age of 65, we included 20 EOAD patients, 20 LOAD patients, and 36 age-matched controls (19 young and 17 old controls). We employed resting-state functional MRI and network centrality analysis to explore the local (degree centrality (DC)) and global (eigenvector centrality (EC)) functional integrity. Two-sample t-test analysis was performed, with gray matter volume, age, gender, and education as covariates. Furthermore, we performed a correlation analysis between network metrics and cognition. Compared to young controls, EOAD patients exhibited lower DC in the middle temporal gyrus (MTG), parahippocampal gyrus (PHG), superior temporal gyrus (STG), and lower EC in the MTG, PHG, and postcentral gyrus. In contrast, LOAD patients exhibited lower DC in the STG and anterior cingulum gyrus and higher DC in the middle frontal gyrus compared to old controls. No significant difference in EC was observed in LOAD patients. Furthermore, both DC and EC correlated with cognitive performance. Our study demonstrated divergent functional network impairments in EOAD and LOAD patients. EOAD patients showed more complex network damage involving both local and global centrality properties, while LOAD patients mainly featured local functional connectivity changes. Such centrality impairments are related to poor cognition, especially regarding memory performance.
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http://dx.doi.org/10.1007/s11682-021-00470-3DOI Listing
April 2021

Analysis of Risk Factors for Thromboembolic Events in 88 Patients with COVID-19 Pneumonia in Wuhan, China: A Retrospective Descriptive Report.

Med Sci Monit 2021 Apr 11;27:e929708. Epub 2021 Apr 11.

Department of Respiratory and Critical Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (mainland).

BACKGROUND Since the outbreak of COVID-19 in December 2019, there have been 96 623 laboratory-confirmed cases and 4784 deaths by December 29 in China. We aimed to analyze the risk factors and the incidence of thrombosis from patients with confirmed COVID-19 pneumonia. MATERIAL AND METHODS Eighty-eight inpatients with confirmed COVID-19 pneumonia were reported (31 critical cases, 33 severe cases, and 24 common cases). The thrombosis risk factor assessment, laboratory results, ultrasonographic findings, and prognoses of these patients were analyzed, and compared among groups with different severity. RESULTS Nineteen of the 88 cases developed DVT (12 critical cases, 7 severe cases, and no common cases). In addition, among the 18 patients who died, 5 were diagnosed with DVT. Positive correlations were observed between the increase in D-dimer level (≥5 µg/mL) and the severity of COVID-19 pneumonia (r=0.679, P<0.01), and between the high Padua score (≥4) and the severity (r=0.799, P<0.01). In addition, the CRP and LDH levels on admission had positive correlations with the severity of illness (CRP: r=0.522, P<0.01; LDH: r=0.600, P<0.01). A negative correlation was observed between the lymphocyte count on admission and the severity of illness (r=-0.523, P<0.01). There was also a negative correlation between the lymphocyte count on admission and mortality in critical patients (r=-0.499, P<0.01). Univariable logistic regression analysis showed that the occurrence of DVT was positively correlated with disease severity (crude odds ratio: 3.643, 95% CI: 1.218-10.896, P<0.05). CONCLUSIONS Our report illustrates that critically or severely ill patients have an associated high D-dimer value and high Padua score, and illustrates that a low threshold to screen for DVT may help improve detection of thromboembolism in these groups of patients, especially in asymptomatic patients. Our results suggest that early administration of prophylactic anticoagulant would benefit the prognosis of critical patients with COVID-19 pneumonia and would likely reduce thromboembolic rates.
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http://dx.doi.org/10.12659/MSM.929708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047776PMC
April 2021

Simultaneous determination of short-chain fatty alcohols in aged oil and biodiesels by stable isotope labeling assisted liquid chromatography-mass spectrometry.

Talanta 2021 Jul 9;229:122223. Epub 2021 Mar 9.

Key Laboratory of Analytical Chemistry of the State Ethnic Affairs Commission, College of Chemistry and Materials Science, South-Central University for Nationalities, Wuhan, 430074, People's Republic of China. Electronic address:

Short-chain fatty alcohols (SCFAs) are one of the reactants for the production of biodiesels. The SCFA residues at the trace level have a significant impact on biodiesel quality. However, the analysis of SCFAs in aged biodiesels has not been reported so far, which is probably due to the unavailability of an appropriate analytical method for the simultaneous determination of SCFAs. Herein, we developed a novel analytical approach with high sensitivity and selectivity for the simultaneous identification and determination of SCFAs in seed oil and biodiesel samples during the simulated real-time aging by stable isotope labeling assisted liquid chromatography-mass spectrometry (SIL-LC-MS). A pair of isotope labeling reagents, pyridine (Py) and [H]pyridine ([H]Py), were used to label SCFAs in biodiesels and standards, respectively. The [H]Py labeled SCFAs were used as internal standards to compensate for the detection of variances. The simultaneous determination of SCFAs was performed by LC-MS with an improved detection selectivity and sensitivity. The limits of detection (LODs) values were ranged from 0.2 to 0.5 ng mL for the investigated SCFAs. Good linearity was observed in the studied ranges (R > 0.99) and good precision with relative standard deviations (RSDs) was in the range of 4.9-18.1%. Average recoveries were obtained in the range of 80.3%-115.4%. The matrix effects were in the range of 70.0-104.3%. The validated SIL-LC-MS method was applied to the simultaneous quantitative analysis of SCFAs in seed oil and biodiesel samples and the LC-MS analysis could be done within 3 min. The formation mechanism of SCFAs in aged oil and biodiesel samples was also investigated by this method. The results suggest that SCFAs were formed and their composition changed during the simulated real-time aging of long-chain fatty acid (LCFA), long-chain fatty acid methyl ester (FAME), seed oil, and biodiesels. Moreover, we found that the formation of 1-pentanol and 1-hexanol was associated with the number and position of double bonds in LCFAs and FAMEs.
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http://dx.doi.org/10.1016/j.talanta.2021.122223DOI Listing
July 2021

The role of extracorporeal membrane oxygenation in critically ill patients with COVID-19: a narrative review.

BMC Pulm Med 2021 Apr 8;21(1):116. Epub 2021 Apr 8.

Department of Anaesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277, Jiefang Avenue, Wuhan, 430022, China.

Extracorporeal life support treatments such as extracorporeal membrane oxygenation (ECMO) have been recommended for the treatment of severe acute respiratory distress syndrome (ARDS) patients with coronavirus disease 2019 (COVID-19). To date, many countries, including China, have adopted ECMO as a treatment for severe COVID-19. However, marked differences in patient survival rates have been reported, and the underlying reasons are unclear. This study aimed to summarize the experience of using ECMO to treat severe COVID-19 and provide suggestions for improving ECMO management. The effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the pathophysiology of COVID-19 and the effects of ECMO on the clinical outcomes in patients with severe cases of COVID-19 were reviewed. Recent data from frontline workers involved in the use of ECMO in Wuhan, China, and those experienced in the implementation of artificial heart and lung support strategies were analysed. There is evidence that ECMO may complicate the pathophysiological state in COVID-19 patients. However, many studies have shown that the appropriate application of ECMO improves the prognosis of such patients. To expand our understanding of the benefits of ECMO for critically ill patients with COVID-19, further prospective, multicentre clinical trials are needed.
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http://dx.doi.org/10.1186/s12890-021-01479-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027981PMC
April 2021
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