Publications by authors named "Liang Huang"

681 Publications

Successful treatment of severe myocardial injury complicated with refractory cardiogenic shock caused by AOPP using extracorporeal membrane oxygenation: A case report.

Medicine (Baltimore) 2021 Jun;100(23):e26318

Department of Emergency Medicine, The First Affiliated Hospital of Nanchang University, Donghu District, Nanchang, Jiangxi Province, China.

Rationale: Acute organophosphorus pesticide poisoning (AOPP) is a common critical illness observed in clinical practice, and severe AOPP can cause serious cardiac toxicity.

Patient Concerns: This patient was a 43-year-old woman who was admitted to the emergency department with acute respiratory failure and hypotension 13 hours after oral consumption of 300 mL of phoxim pesticide.

Diagnoses: Acute organophosphorus pesticide poisoning, cardiogenic shock.

Interventions: We conducted veno-arterial extracorporeal membrane oxygenation (VA-ECMO) therapy as the patient did not respond to conventional measures.

Outcomes: This patient was successfully rescued with VA-ECMO therapy and discharged.

Lessons: We suggest that for patients with severe myocardial injury complicated with cardiogenic shock caused by AOPP, the use of VA-ECMO therapy can improve the prognosis.
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http://dx.doi.org/10.1097/MD.0000000000026318DOI Listing
June 2021

Glucose-oxidase like catalytic mechanism of noble metal nanozymes.

Nat Commun 2021 06 7;12(1):3375. Epub 2021 Jun 7.

State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Jilin, PR China.

Au nanoparticles (NPs) have been found to be excellent glucose oxidase mimics, while the catalytic processes have rarely been studied. Here, we reveal that the process of glucose oxidation catalyzed by Au NPs is as the same as that of natural glucose oxidase, namely, a two-step reaction including the dehydrogenation of glucose and the subsequent reduction of O to HO by two electrons. Pt, Pd, Ru, Rh, and Ir NPs can also catalyze the dehydrogenation of glucose, except that O is preferably reduced to HO. By the electron transfer feature of noble metal NPs, we overcame the limitation that HO must be produced in the traditional two-step glucose assay and realize the rapid colorimetric detections of glucose. Inspired by the electron transport pathway in the catalytic process of natural enzymes, noble metal NPs have also been found to mimic various enzymatic electron transfer reactions including cytochrome c, coenzymes as well as nitrobenzene reductions.
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http://dx.doi.org/10.1038/s41467-021-23737-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184917PMC
June 2021

Atomic engineering of single-atom nanozymes for enzyme-like catalysis.

Chem Sci 2020 Aug 11;11(36):9741-9756. Epub 2020 Aug 11.

State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences Changchun Jilin 130022 China

Enzyme mimics, especially nanozymes, play a crucial role in replacing natural enzymes for diverse applications related to bioanalysis, therapeutics and other enzyme-like catalysis. Nanozymes are catalytic nanomaterials with enzyme-like properties, which currently face formidable challenges with respect to their intricate structure, properties and mechanism in comparison with enzymes. The latest emergence of single-atom nanozymes (SAzymes) undoubtedly promoted the nanozyme technologies to the atomic level and provided new opportunities to break through their inherent limitations. In this perspective, we discuss key aspects of SAzymes, including the advantages of the single-site structure, and the derived synergetic enhancements of enzyme-like activity, catalytic selectivity and the mechanism, as well as the superiority in biological and catalytic applications, and then highlight challenges that SAzymes face and provide relevant guidelines from our point of view for the rational design and extensive applications of SAzymes, so that SAzyme may achieve its full potential as the next-generation nanozyme.
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http://dx.doi.org/10.1039/d0sc03522jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162425PMC
August 2020

Deep Scoring Neural Network Replacing the Scoring Function Components to Improve the Performance of Structure-Based Molecular Docking.

ACS Chem Neurosci 2021 Jun 3. Epub 2021 Jun 3.

Institute of Modern Physics, Chinese Academy of Science, Lanzhou 730000, China.

Accurate prediction of protein-ligand interactions can greatly promote drug development. Recently, a number of deep-learning-based methods have been proposed to predict protein-ligand binding affinities. However, these methods independently extract the feature representations of proteins and ligands but ignore the relative spatial positions and interaction pairs between them. Here, we propose a virtual screening method based on deep learning, called Deep Scoring, which directly extracts the relative position information and atomic attribute information on proteins and ligands from the docking poses. Furthermore, we use two Resnets to extract the features of ligand atoms and protein residues, respectively, and generate an atom-residue interaction matrix to learn the underlying principles of the interactions between proteins and ligands. This is then followed by a dual attention network (DAN) to generate the attention for two related entities (i.e., proteins and ligands) and to weigh the contributions of each atom and residue to binding affinity prediction. As a result, Deep Scoring outperforms other structure-based deep learning methods in terms of screening performance (area under the receiver operating characteristic curve (AUC) of 0.901 for an unbiased DUD-E version), pose prediction (AUC of 0.935 for PDBbind test set), and generalization ability (AUC of 0.803 for the CHEMBL data set). Finally, Deep Scoring was used to select novel ERK2 inhibitor, and two compounds (D264-0698 and D483-1785) were obtained with potential inhibitory activity on ERK2 through the biological experiments.
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http://dx.doi.org/10.1021/acschemneuro.1c00110DOI Listing
June 2021

MYC/BCL2/BCL6 triple hit and TP53 deletion in a case of high-grade B cell lymphoma receiving CAR T cell immunotherapy.

J Immunother Cancer 2021 Jun;9(6)

Department of Hematology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China.

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http://dx.doi.org/10.1136/jitc-2020-002029DOI Listing
June 2021

FeS nanoparticles decorated carbonized Luffa cylindrica as biofilm substrates for fabricating high performance biosensors.

Talanta 2021 Sep 19;232:122416. Epub 2021 Apr 19.

State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China; University of the Chinese Academy of Sciences, Beijing, 100049, PR China. Electronic address:

A high-performance microbial biosensor was fabricated with a reasonably designed biofilm substrate, where the aerogel of carbonized Luffa cylindrica (LC) was used as the scaffold for loading biofilm and FeS nanoparticles (FeSNPs) were employed to modify this aerogel (FeSNPs/Gel). The fabricated FeSNPs/Gel exhibited a spring-like structure similar with that of the raw LC, which facilitated the linkage of the scaffold and promoted its mechanical strength, and further prolonged the service period of the as-prepared biosensor from few days to two months. Meanwhile, the introduced FeSNPs improved the microbial electron transfer of the biofilm and causing an increase in the sensor's signals from 155.0 ± 2.6 to 352.0 ± 17.1 nA and a decrease in the detection limit from 0.95 to 0.38 mg O L (S/N = 3) for the detection of glucose-glutamic acid (GGA). More important, the FeSNPs had been demonstrated to have the capability for modulating a persistent shift of the microbial community with organic pollutant biodegradability. Compared with the Gel, the FeSNPs/Gel exhibited a promising performance for measuring the synthetic sewage and real water samples in BOD assay and an increasing inhibition-ratio for detecting 3,5-dichlorophenol (DCP) in toxicity assay. Based on the vast resource and renewability of LC, this work pave a new avenue for developing high-performance microbial biosensors that are expected to be the engineering production.
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http://dx.doi.org/10.1016/j.talanta.2021.122416DOI Listing
September 2021

-Mutated Circulating Tumor DNA for Disease Monitoring in Lymphoma Patients after CAR T Cell Therapy.

Diagnostics (Basel) 2021 May 8;11(5). Epub 2021 May 8.

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Chimeric antigen receptor T (CAR T) cell immunotherapy has shown remarkable efficacy in non-Hodgkin's lymphoma (NHL) patients. Minimal residual disease (MRD) monitoring in NHL is essential after CAR T cell therapy, which can be achieved by monitoring circulating tumor DNA (ctDNA). The mutation of in NHL has been suggested to be associated with a poor prognosis. However, whether -mutated ctDNA can be used as a biomarker remains undetermined. In this study, a total of 40 patients with mutated who received CAR T cell treatment were analyzed, and specific probes targeting 29 different mutation sites in the 40 patients were designed and verified. Then, the presence of -mutated ctDNA in longitudinal plasma samples was tracked by droplet digital PCR. Patients were stratified into two groups, favorable or unfavorable, based on their highest ctDNA level using a MAF cutoff of 3.15% according to the ROC curve. The unfavorable group had significantly worse PFS than the favorable group ( < 0.001). Our results suggest that patients with mutated with a favorable ctDNA profile in the first trimester have better prognostic outcomes than patients with an unfavorable profile, and ctDNA can be a reliable predictor of the subsequent clinical outcome.
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http://dx.doi.org/10.3390/diagnostics11050844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151854PMC
May 2021

Successful treatment of a patient with recurrent infection of Chromobacterium violaceum.

BMC Infect Dis 2021 May 26;21(1):484. Epub 2021 May 26.

Department of Dermatology, Southern Medical University Nanfang Hospital, Guangzhou, 510515, China.

Background: Chromobacterium violaceum (C. violaceum) is a Gram-negative saprophytic bacterium that is widespread in tropical and subtropical environments, and belongs to conditional pathogenic bacteria. Human infection with C. violaceum is rare, and this can be fatal when the diagnosis and treatment are delayed, especially recurrent infection patients. Since clinicians lack the knowledge for C. violaceum, rapid diagnosis and early appropriate antimicrobial treatment remains challenging.

Case Presentation: A 15-year-old male student was hospitalized for dark abscess, pustules, severe pain in both legs, and fever for 11 days. There were pustules with gray-white pus and red infiltrating plaques on the back, and the subcutaneous nodules could be touched in front of both tibias, with scab, rupture and necrotic tissue of the lower limb. The patient's condition rapidly progressed. Therefore, next-generation sequencing (NGS), pustular secretion and blood culture were concurrently performed. The final diagnosis for this patient was C. violaceum infection by NGS. However, no bacterial or fungal growth was observed in the pustular secretion and blood culture. After 4 weeks of treatment, the patient was discharged from the hospital without any complications associated with C. violaceum infection.

Conclusion: Rapid diagnosis and early appropriate antimicrobial treatment is the key to the successful treatment of C. violaceum infection, especially in patients with sepsis symptoms. This case highlights that NGS is a promising tool for the rapid diagnosis of C. violaceum infection, preventing the delayed diagnosis and misdiagnosis of C. violaceum infection in patients who tested negative for pustular secretion and blood culture.
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http://dx.doi.org/10.1186/s12879-021-06216-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157692PMC
May 2021

Compact Magneto-Fluorescent Colloids by Hierarchical Assembly of Dual-Components in Radial Channels for Sensitive Point-of-Care Immunoassay.

Small 2021 May 25:e2100862. Epub 2021 May 25.

College of Chemical Engineering, Zhejiang University of Technology, Hangzhou, 310014, P. R. China.

Exploring signal amplification strategies to enhance the sensitivity of lateral flow immunoassay (LFIA) is of great significance for point-of-care (POC) testing of low-concentrated targets in the field of in vitro diagnostics. Here, a highly-sensitive LFIA platform using compact and hierarchical magneto-fluorescent assemblies as both target-enrichment substrates and optical sensing labels is demonstrated. The large-pored dendritic templates are utilized for high-density incorporation of both superparamagnetic iron oxide nanoparticles (IOs) and quantum dots (QDs) within the vertical channels. The hierarchical structure is built via affinity-driven assembly of IOs and QDs from organic phase with silica surface and mercapto-organosilica intermediate layer, respectively. The sequential assembly with central-radial channels enables 3D loading of dual components and separately controlling of discrete functionalities. After the alkyl-organosilica encapsulation and silica sealing, the composite spheres exhibit high stabilities and compatibility with LFIA for procalcitonin (PCT) detection. With the assistance of liquid-phase antigen-capturing, magnetic enrichment, and fluorescence-signal amplification, a limit of detection of 0.031 ng mL for PCT is achieved with a linear range from 0.012 to 10 ng mL . The current LFIA is robust and validated for PCT detection in real serum, which holds great diagnostic significance for precise guidance of antibiotic therapy with POC manner.
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http://dx.doi.org/10.1002/smll.202100862DOI Listing
May 2021

Effects of N-terminal modifications on the stability of antimicrobial peptide SAMP-A4 analogues against protease degradation.

J Pept Sci 2021 May 24:e3352. Epub 2021 May 24.

College of Biological Engineering, Henan University of Technology, Zhengzhou, China.

Infections with multidrug-resistant (MDR) pathogens are increasingly concerning for public health. Synthesized antimicrobial peptide A4 (SAMP-A4), a peptide computationally designed by our research team, is a potential drug candidate. However, the antimicrobial peptide SAMP-A4 is easily degraded in serum. To obtain SAMP-A4 analogues with high biostability, chemical modifications at its N-terminus, including fatty acid conjugation, glycosylation and PEGylation, were carried out. The results showed that the introduction of hydrophobic fatty acids at the N-terminus of SAMP-A4 is better than hydrophilic glycosylation and PEGylation. With increasing fatty acid chain length, the stability of SAMP-A4 analogues in serum and trypsin solutions is significantly improved, and the activities against MDR bacteria and Candida are significantly enhanced. There is no obvious change in haemolysis even when hexanoic acid is coupled with SAMP-A4, so the resulting analogue SAMP-A4-C6, SAMP-A4 conjugated with hexanoic acid, is the most likely of the analogues to become a drug.
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http://dx.doi.org/10.1002/psc.3352DOI Listing
May 2021

Distinct Genomic Landscape of Colorectal Mucinous Carcinoma Determined Comprehensive Genomic Profiling: Steps to a New Treatment Strategy.

Front Oncol 2021 7;11:603564. Epub 2021 May 7.

Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Colorectal mucinous carcinoma (MC) is associated with inferior prognosis and response to treatment compared to adenocarcinoma (AC). The molecular landscapes of MC and adenocarcinoma with mucous composition (AMC) are not well-defined. We aimed to describe the genomic landscape of MC and AMC in a large colorectal cancer cohort. Tumor samples from patients with MC, AMC, or AC were analyzed using next-generation sequencing. MC had a molecular signature distinct from that of AC; genomic features were similar between AMC and MC but not between AMC and AC. amplification and and mutation rates were lower, whereas , , , , , , , V600E, , and mutation rates were higher in MC than in AC. The mutation frequencies in MAPK, PI3K, and TGF- pathways were higher, whereas those of cell cycle proteins and Wnt were lower in MC and AMC than in AC. The proportion of hypermutated tumors was significantly higher in MC and AMC than in AC. As MC has a distinct molecular signature from AC, immunotherapy can be potentially applied in treating MC. Similar molecular profiles of AMC and MC suggest that treatment strategies for MC, but not AC, can be used for AMC treatment.
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http://dx.doi.org/10.3389/fonc.2021.603564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139246PMC
May 2021

Chemerin in atherosclerosis.

Clin Chim Acta 2021 May 20;520:8-15. Epub 2021 May 20.

Research Laboratory of Translational Medicine, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, People's Republic of China. Electronic address:

Atherosclerosis (AS), a chronic arterial disease, is characterized by endothelial dysfunction, inflammatory reactions and lipid accumulation in parallel with aberrant angiogenesis and vascular smooth muscle cell (VSMC) proliferation. Adipose tissue has been suggested to have an integral influence on metabolism and endocrine secretion, while there have been increasing concerns about the possible involvement of adipokines in cardiovascular diseases, including AS. Here, we focused on chemerin, an adipokine highly expressed in adipose tissue, with strong evidence of an association with inflammation, endothelial dysfunction, metabolic disorder, aberrant angiogenesis, VSMC proliferation and calcification. In this review, we discuss chemerin and its receptors in the pathogenesis of AS. However, the existing data assign various, even contradictory, roles to chemerin in atherosclerosis, such as inhibiting vascular calcification and impairing endothelial function. Current studies focusing on its anti- and pro-atherogenic effects have pinpointed its distinct role in specific cell types and contexts in the pathogenesis of atherosclerosis. Therefore, the gaps in current knowledge regarding the specific role played by chemerin in the etiology of AS require additional future studies. It seems reasonable to suggest that targeted chemerin therapy can be developed as an innovative approach for treating AS.
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http://dx.doi.org/10.1016/j.cca.2021.05.015DOI Listing
May 2021

Ultrasonic scalpel combined with internal oxygen assisted sodium nitroprusside in laparoscopic cholecystectomy for elderly patients with acute cholecystitis.

Am J Transl Res 2021 15;13(4):3093-3101. Epub 2021 Apr 15.

Shanghai Tenth People's Hospital Shanghai 200072, China.

To analyze the application value of an ultrasonic scalpel combined with internal oxygen assisted intravenous drip of sodium nitroprusside in laparoscopic cholecystectomy for elderly patients with acute cholecystitis.

Methods: A total of 76 patients with acute cholecystitis who were admitted to our hospital from January 2017 to December 2018 were included and equally divided into two groups. The control group was treated with ultrasonic scalpel alone, while the study group was treated with ultrasonic scalpel combined with internal oxygen and intravenous drip of sodium nitroprusside. The incidence of postoperative adverse reactions, the recovery of surgical indicators, the quality of life score before and after treatment, and the changes of serum sICAM-1 and IL-6 expression were observed.

Results: The incidence of postoperative adverse reactions in the study group was significantly higher than that in the control group (P < 0.05); and the recovery of surgical indicators in the study group was better than that in the control group (P < 0.05). After treatment, the levels of serum sICAM-1 and IL-6 in the two groups showed a certain degree of decline, and the levels of serum sICAM-1 and IL-6 inflammatory factors in the study group were significantly lower than those in the control group (P < 0.05). After treatment, the scores of psychological state, physical health, independent ability, social relationship, surrounding environment and personal belief of the two groups were significantly higher than those before treatment (P < 0.05). After treatment, the scores of each field in the treatment group were significantly higher than that in the control group (P < 0.05).

Conclusion: It is safe and feasible to use an ultrasonic scalpel combined with internal oxygen to assist intravenous drip of sodium nitroprusside in the treatment of elderly patients with acute cholecystitis, but proper operation time and skilled operation are necessary.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129297PMC
April 2021

N-terminal acetylation of antimicrobial peptide L163 improves its stability against protease degradation.

J Pept Sci 2021 May 13:e3337. Epub 2021 May 13.

College of Information Science and Engineering, Henan University of Technology, Zhengzhou, China.

Antimicrobial peptide L163 was computationally designed by our laboratory; L163 is active against multidrug-resistant (MDR) bacteria but is easily degraded in the plasma and by trypsin. Amino acid substitution, cyclization, and amino-terminal (N-terminal) acetylation were performed to obtain L163 analogs with high stability in the plasma and in trypsin solutions. The stability, antimicrobial activity, and biosafety of L163 and its analogs were investigated. Comparison with unmodified L163 indicated that N-terminal acetylation enhanced the stability against pH, plasma, and trypsin degradation, and phenylalanine (Phe) substitution for leucine (Leu) and cysteine bridge (S-S) cyclization decreased the stability. N-terminal acetylation also enhanced antimicrobial activity against MDR Streptococcus Sc181, Listeria monocytogenes, and Enterococcus E1478F; did not change the activity against MDR Staphylococcus aureus 9, Staphylococcus sciuri P254, and Staphylococcus aureus RN4220; and decreased the activity against Candida tropicalis, Candida albicans, and Enterococcus faecalis Fbc35. Phe substitution for Leu and S-S cyclization decreased the antimicrobial activity. The negative effect of these modifications was detected against biofilm formation by the tested microbial strains. Comparison of Phe substitution for Leu and S-S cyclization indicated that N-terminally acetylated L163 (L163-Ac) is the best candidate. L163-Ac peptide had the highest antibacterial activity and enhanced tolerance to temperature, pH, plasma, and trypsin and low toxicity.
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http://dx.doi.org/10.1002/psc.3337DOI Listing
May 2021

Internalization and membrane activity of the antimicrobial peptide CGA-N12.

Biochem J 2021 May;478(10):1907-1919

College of Bioengineering, Henan University of Technology, Zhengzhou, Henan 450001, P. R. China.

Antimicrobial peptides (AMPs) are conventional antibiotic alternatives due to their broad-spectrum antimicrobial activities and special mechanisms of action against pathogens. The antifungal peptide CGA-N12 was originally derived from human chromogranin A (CGA) and consists of the 65th to 76th amino acids of the CGA N-terminal region. In the present study, we found that CGA-N12 had fungicidal activity and exhibited time-dependent inhibition activity against Candida tropicalis. CGA-N12 entered the cells to exert its antagonist activity. The internalization of CGA-N12 was energy-dependent and accompanied by actin cytoskeleton-, clathrin-, sulfate proteoglycan-, endosome-, and lipid-depleting agent-mediated endocytosis. Moreover, the CGA-N12 internalization pathway was related to the peptide concentration. The effects of CGA-N12 on the cell membrane were investigated. CGA-N12 at a low concentration less than 4 × MIC100 did not destroy the cell membrane. While with increasing concentration, the damage to the cell membrane caused by CGA-N12 became more serious. At concentrations greater than 4 × MIC100, CGA-N12 destroyed the cell membrane integrity. Therefore, the membrane activity of CGA-N12 is concentration dependant.
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http://dx.doi.org/10.1042/BCJ20201006DOI Listing
May 2021

Corrigendum to "Evaluation of structure transformation and biocompatibility of chitosan in alkali/urea dissolution system for its large-scale application" [Int. J. Biol. Macromol. Volume 154, 1 July 2020, pages 758-764].

Int J Biol Macromol 2021 Apr 26. Epub 2021 Apr 26.

College of Marine Life Science, Ocean University of China, 5# Yushan Road, Qingdao 266003, Shandong Province, China; Qingdao National Laboratory for Marine Science and Technology, Qingdao 266000, China. Electronic address:

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http://dx.doi.org/10.1016/j.ijbiomac.2021.03.200DOI Listing
April 2021

Interfacial Electron Engineering of Palladium and Molybdenum Carbide for Highly Efficient Oxygen Reduction.

J Am Chem Soc 2021 May 29;143(18):6933-6941. Epub 2021 Apr 29.

State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China.

Interfacial electron engineering between noble metal and transition metal carbide is identified as a powerful strategy to improve the intrinsic activity of electrocatalytic oxygen reduction reaction (ORR). However, this short-range effect and the huge structural differences make it a significant challenge to obtain the desired electrocatalyst with atomically thin noble metal layers. Here, we demonstrated the combinatorial strategies to fabricate the heterostructure electrocatalyst of MoC-coupled Pd atomic layers (AL-Pd/MoC) by precise control of metal-organic framework confinement and covalent interaction. Both atomic characterizations and density functional theory calculations uncovered that the strong electron effect imposed on Pd atomic layers has intensively regulated the electronic structures and d-band center and then optimized the reaction kinetics. Remarkably, AL-Pd/MoC showed the highest ORR electrochemical activity and stability, which delivered a mass activity of 2.055 A mg at 0.9 V, which is 22.1, 36.1, and 80.3 times higher than Pt/C, Pd/C, and Pd nanoparticles, respectively. The present work has developed a novel approach for atomically noble metal catalysts and provides new insights into interfacial electron regulation.
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http://dx.doi.org/10.1021/jacs.1c00656DOI Listing
May 2021

Clinical Utility of Droplet Digital PCR to Monitor BCR-ABL1 Transcripts of Patients With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Post-chimeric Antigen Receptor19/22 T-Cell Cocktail Therapy.

Front Oncol 2021 7;11:646499. Epub 2021 Apr 7.

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph ALL) accounts for 20-30% of adult patients with ALL, characterized by translocation of . Tyrosine kinase inhibitors (TKIs) have significantly improved the outcome even though there are still some problems including relapse due to drug-resistant mutations and suboptimal molecular remission depth. Previously, we reported the safety and efficacy of sequential infusion of CD19/22 chimeric antigen receptor T-cell (CAR-T) immunotherapy in the treatment of relapsed/refractory (R/R) B-cell neoplasms including cases with Ph ALL. Given possible deeper reaction, more patients were expected to reach optimal minimal residual disease (MRD) response. An alternative method, duplex droplet digital PCR (ddPCR) with high sensitivity was established, which could provide absolute quantification of MRD without the need for calibration curves. Here, we retrospectively collected 95 bone marrow samples from 10 patients with R/R Ph, who received 19/22 CAR-T-cell cocktail therapy. Notably, sequential molecular remission for more than 3 months (SMR3), a significant indicator based on ddPCR after CAR-T infusion was established, which was defined as a sequential molecular remission for not <3 months with negative MRD. In this cohort, no recurrence was observed in six patients achieving SMR3, where four of whom accepted allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CAR-T cell regimen. Unfortunately, the other four patients who did not reach SMR3 relapsed, and did not receive extra specific treatment except CAR-T regimen. To sum up, ddPCR may be an alternative, especially when nucleic acid was insufficient in clinical practice. No achievement of SMR3 may be an early warning of potential relapse after CAR-T and indicating the initiation of other therapies including allo-HSCT.
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http://dx.doi.org/10.3389/fonc.2021.646499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059437PMC
April 2021

Establishment of a homogeneous immunoassay-light-initiated chemiluminescence assay for detecting anti-Müllerian hormone in human serum.

J Immunol Methods 2021 Jul 22;494:113059. Epub 2021 Apr 22.

School of Medical Laboratory, Tianjin Medical University, Tianjin 300203, China. Electronic address:

Anti-Müllerian hormone (AMH) is known as a reliable marker of ovarian reserve (OR). The determination of AMH is of great importance and most existed AMH detection methods are heterogeneous immunoassay. In this study, a novel homogeneous sandwich immunoassay-light-initiated chemiluminescence assay (LICA) for detecting AMH serum level was developed. This AMH-LICA was performed by incubating serum samples with AMH mouse monoclonal antibody coated with chemibeads, streptavidin-coated sensibeads, and biotinylated AMH mouse monoclonal antibody. Sensitivity, precision, accuracy and cross-reactivity of this assay were evaluated. Besides, a regression analysis showed a high correlation between AMH-LICA and Roche Elecsys® AMH assay (y = 0.9851x + 0.07147, R = 0.9569). As a homogeneous immunoassay, this AMH-LICA could accurately and rapidly determine the serum level of AMH with high-throughput. Thus, this new developed assay may be a new useful analytical tool for the determination of AMH.
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http://dx.doi.org/10.1016/j.jim.2021.113059DOI Listing
July 2021

Oxidative stress in vascular calcification.

Clin Chim Acta 2021 Aug 20;519:101-110. Epub 2021 Apr 20.

Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, People's Republic of China. Electronic address:

Vascular calcification (VC), which is closely associated with significant mortality in cardiovascular disease, chronic kidney disease (CKD), and/or diabetes mellitus, is characterized by abnormal deposits of hydroxyapatite minerals in the arterial wall. The impact of oxidative stress (OS) on the onset and progression of VC has not been well described. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, xanthine oxidases, myeloperoxidase (MPO), nitric oxide synthases (NOSs), superoxide dismutase (SOD) and paraoxonases (PONs) are relevant factors that influence the production of reactive oxygen species (ROS). Furthermore, excess ROS-induced OS has emerged as a critical mediator promoting VC through several mechanisms, including phosphate balance, differentiation of vascular smooth muscle cells (VSMCs), inflammation, DNA damage, and extracellular matrix remodeling. Because OS is a significant regulator of VC, antioxidants may be considered as novel treatment options.
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http://dx.doi.org/10.1016/j.cca.2021.04.012DOI Listing
August 2021

Extracorporeal membrane oxygenation combined with sequential blood purification in the treatment of myocardial damage and cardiac arrest caused by mushroom poisoning.

Toxicon 2021 Jul 17;197:65-69. Epub 2021 Apr 17.

Department of Emergency Medicine, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Donghu District, Nanchang, 330006, Jiangxi Province, China. Electronic address:

Mushroom poisoning is a common clinical problem. Severe mushroom poisoning often causes liver and kidney failure. Although severe myocardial damage is rare, the fatality rate is extremely high. This case report describes a 56-year-old male suffered severe myocardial damage, multiple organ dysfunction, circulatory failure, recurrent malignant arrhythmia, and cardiac arrest after the ingestion of wild mushrooms. He was administered venoarterial extracorporeal membrane oxygenation (VA-ECMO) combined with hemoperfusion, plasma exchange and continuous renal replacement therapy. The heart rhythm gradually stabilized 3 hours after ECMO surgery. On the 6th day after ECMO, heart function recovered. The patient was then weaned from ECMO, and he ultimately recovered and was discharged. In patients with fatal mushroom poisoning leading to refractory arrhythmia and cardiac arrest, early implementation of VA-ECMO combined with sequential blood purification treatment can improve the prognosis and increase the survival rate.
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http://dx.doi.org/10.1016/j.toxicon.2021.04.011DOI Listing
July 2021

Reinduction chemotherapy regimen involved decitabine and cladribine improves the prognosis of patients with relapsed or refractory acute myeloid leukemia: A preliminary study.

Int J Cancer 2021 Apr 9. Epub 2021 Apr 9.

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Relapsed/refractory acute myeloid leukemia (R/R-AML) is characterized by a high incidence, short survival and poor prognosis. Presently, no unified effective reinduction chemotherapy regimen has been developed. Therefore, the use of reinduction chemotherapy regimens before allogeneic hematopoietic stem cell transplantation (allo-HSCT) is controversial. Our study aims to analyze the prognostic factors of R/R-AML and to evaluate the efficacy of the regimen involved decitabine, cladribine, idarubicin or homoharringtonine, and cytarabine (DCIA/DCHA). Clinical and survival data of 112 R/R-AML patients were obtained. Among the 102 R/R-AML patients that were treated with conventional regimens, we found that poor prognosis was related to a greater proportion of bone marrow blasts (>70%) and not achieving complete remission (non-CR) after the first reinduction chemotherapy. Hematopoietic stem cell transplantation (of which 89.47% was allo-HSCT) following CR after the first reinduction chemotherapy often improves the prognosis. Of the 10 R/R-AML patients that were treated with the DCIA/DCHA regimen, nine patients achieved CR or complete response with incomplete hematopoietic recovery (CRi) after one course of chemotherapy. The median overall survival of the 10 patients was 10.14 (1.23-29.13) months. In conclusion, non-CR was associated with poor prognosis in R/R-AML. Therefore, intensive reinduction chemotherapy should be selected to achieve CR. This creates conditions for allo-HSCT and improves prognosis of R/R-AML patients. The DCIA/DCHA regimen showed good efficacy and tolerable adverse reactions in R/R-AML treatment. This combination may be used as a bridging regimen for allo-HSCT in R/R-AML.
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http://dx.doi.org/10.1002/ijc.33595DOI Listing
April 2021

Ratiometric Fluorescent Lateral Flow Immunoassay for Point-of-Care Testing of Acute Myocardial Infarction.

Angew Chem Int Ed Engl 2021 Jun 5;60(23):13042-13049. Epub 2021 May 5.

College of Chemical Engineering, Zhejiang University of Technology, Hangzhou, 310014, PR China.

We report the development of a highly sensitive ratiometric fluorescent lateral flow immunoassay (RFLFIA) strip for rapid and accurate detection of acute myocardial infarction biomarker, namely heart-type fatty acid binding protein (H-FABP). The RFLFIA strip works in terms of ratiometric change of fluorescence signal, arising from blending of fluorescence emitted by two composite nanostructures conjugated to capture and probe antibodies and inner filter effect of gold nanoparticles. In conjunction with using custom smartphone-based analytical device and tonality analysis, quantitative detection of H-FABP was achieved with a low limit of detection at 0.21 ng mL . The RFLFIA strip can generate a visually distinguishable green-to-red color change around the threshold concentration of H-FABP (6.2 ng mL ), thus allowing the semi-quantitative diagnosis by the naked eye.
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http://dx.doi.org/10.1002/anie.202103458DOI Listing
June 2021

Sucrose enhanced reactive oxygen species generation promotes cotton fibre initiation and secondary cell wall deposition.

Plant Biotechnol J 2021 Jun 2;19(6):1092-1094. Epub 2021 Jun 2.

Chongqing Key Laboratory of Application and Safety Control of Genetically Modified Crops, Biotechnology Research Center, Southwest University, Chongqing, China.

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http://dx.doi.org/10.1111/pbi.13594DOI Listing
June 2021

A phase I study of anti-BCMA CAR T cell therapy in relapsed/refractory multiple myeloma and plasma cell leukemia.

Clin Transl Med 2021 Mar;11(3):e346

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Background: Relapsed/refractory (R/R) multiple myeloma (MM) patients and primary plasma cell leukemia (PCL) have an unfavorable prognosis and no effective treatment. This study was designed to assess the safety and preliminary efficacy of a novel anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell in R/R MM and PCL.

Methods: Between February 22, 2017, and June 25, 2018, 28 R/R and two R/R primary PCL patients received a median dose of 11.2 × 10 CAR+ cells/kg. The subjects were refractory to a proteasome inhibitor and/or an immunomodulatory agent. Fludarabine and cyclophosphamide were given as lymphodepletion chemotherapy.

Results: Results for these 30 consecutive patients who received an anti-BCMA CAR T cell infusion are reported. The patients had received a median of four prior lines of therapy. A total of 44 different types of adverse events were recorded, and hematologic toxic effects were the most common events of any grade during treatment. Hematologic toxic effects were also the most common events of grade 3 or higher. A total of 29 patients (96.7%) had cytokine release syndrome, which was of grade 1 or 2 in 24 patients (80%) and grade 3 in five patients (16.7%). Neurologic toxic effects only occurred in one patient (3.3%) and were of grade 1. The objective response rate was 90%, and the complete response rate was 43.3%. With a median follow-up of 12.6 months, the median progression-free survival (PFS) and overall survival were 5.2 months and 14.0 months. One of the two primary PCL achieved a complete response with a PFS of 307 days. The other patients achieved a very good partial response with a PFS of 117 days.

Conclusions: Anti-BCMA CAR T cell treatment is safe and highly active in R/R multiple myeloma.
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http://dx.doi.org/10.1002/ctm2.346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943908PMC
March 2021

Transanal vs laparoscopic total mesorectal excision for rectal cancer: a multicenter randomized phase III clinical trial (TaLaR trial) protocol.

Gastroenterol Rep (Oxf) 2021 Jan 14;9(1):71-76. Epub 2020 Dec 14.

Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China.

Background: Total mesorectum excision (TME) is considered the standard surgical procedure for rectal-cancer treatment. Transanal TME (taTME) is a new procedure to treat low rectal cancer. Some published studies have proven that taTME can provide a better-quality resected specimen in low-rectal-cancer patients in comparison to the transabdominal procedure, yet long-term outcomes must be investigated. We designed this non-inferiority trial (TaLaR trial) to compare short-term and long-term outcomes between taTME and laparoscopic TME (lapTME) for rectal cancer.

Methods: The TaLaR trial is a phase III open-labeled multicenter randomized-controlled trial. Patients who are diagnosed with rectal cancer with no more than T3N2 stage, and with the tumor location below the peritoneal reflection by magnetic resonance imaging scan, digital rectal examination, or colonoscopy, qualify for this study. After calculating, a total of 1,114 patients (557 per group) will be randomly allocated to either the taTME or the lapTME group. Primary endpoints are the 3-year disease-free survival (DFS) rate and the 5-year overall survival (OS) rate. Secondary endpoints include specimen quality, perioperative results, pelvic and anal function, and quality of life.

Discussion: The TaLaR trial is expected to clarify whether taTME can achieve comparable oncological outcomes, as well as improve specimen quality and recovery conditions in rectal-cancer patients compared with lapTME.
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http://dx.doi.org/10.1093/gastro/goaa083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962745PMC
January 2021

Risk factors and clinical outcomes of extrahepatic recurrence in patients with post-hepatectomy recurrent hepatocellular carcinoma.

ANZ J Surg 2021 Jun 16;91(6):1174-1179. Epub 2021 Mar 16.

Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Background: Extrahepatic recurrence remains a major obstacle to an improved prognosis in patients with hepatocellular carcinoma (HCC) undergoing hepatectomy.

Methods: From January 2001 to December 2014, we screened 1330 consecutive patients who underwent curative hepatectomy for HCC. Patients who experienced recurrence were enrolled in this study and divided into an extrahepatic recurrence (EHR) group and a pure intrahepatic recurrence (IHR) group. Clinical data and follow-up results were retrospectively collected and analysed.

Results: A total of 556 patients were enrolled (EHR, 52; IHR, 504). In the EHR group, the lung was the most common site of extrahepatic recurrence (53.8%), among which 67.3% had associated intrahepatic lesions. Background Hepatitis B (HR 0.282; 95% CI 0.106-0.752; P = 0.011), tumour size ≥10 cm at initial diagnosis (HR 2.679; 95% CI 1.283-5.596; P = 0.009) and blood transfusion during initial surgery (HR 2.218; 95% CI 1.132-4.346; P = 0.020) were predictive of EHR. A multidisciplinary team treated recurrent HCC. After a median follow-up period of 46 months (range, 24-192 months), the 1-, 3- and 5-year overall survival rates in the EHR group were 60.7%, 8.9% and 0%, respectively, after recurrence, and 78.8%, 30.2% and 8.9%, respectively, after initial surgery, which were much lower than those in the IHR group.

Conclusion: Tumour size ≥10 cm and blood transfusion during initial surgery were predictive of extrahepatic recurrence in patients with post-hepatectomy recurrent HCC. Treatment options were limited, and long-term survival was unsatisfactory.
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http://dx.doi.org/10.1111/ans.16737DOI Listing
June 2021

A predictor of pathological complete response to neoadjuvant chemotherapy in triple-negative breast cancer patients with the DNA repair genes.

Ann Transl Med 2021 Feb;9(4):301

Department of Breast Surgery, Fudan University Shanghai Cancer Center/Cancer Institute, Shanghai, China.

Background: We conducted this study to investigate the prevalence of potential chemo-response-related gene mutations in triple-negative breast cancer (TNBC) patients and to evaluate the potential relationship between these gene mutations and neoadjuvant chemotherapy response in TNBC patients.

Methods: One hundred sixty-two TNBC patients in Fudan University Shanghai Cancer Center who received NAC with 4 cycles of paclitaxel and carboplatin were enrolled in this study. Fifty-six pathological complete response (pCR) patients and 56 non-pCR patients were enrolled in this retrospective study for the training set. Clinical assessments of postoperative residual tumors were performed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Forty chemo-response-related genes were screened in each tumor specimen by second-generation sequencing analysis. Fifty TNBC patients who received neoadjuvant chemotherapy with paclitaxel and carboplatin were enrolled in the validation group.

Results: Fifty-seven of 112 (50.9%) TNBCs contained at least one detected somatic mutation. As expected, mutation was the most common alteration, which was observed in 21.4% of patients. , , , , and mutations were each observed in 11.6%, 4.5%, 5.4%, 2.7% and 3.6% of all cases, respectively. No significant differences in any gene mutation frequency between pCR and non-pCR groups were identified. We found that the mutation status of 10 DNA repair genes involved in homologous recombination (HR) pathway successfully discriminated between responding and nonresponding tumors in the training group. Up to 18 patients who were mutation-positive experienced pCR compared to only 6 in the non-pCR group (P=0.006), and 75% the HR related gene mutation patients achieved pCR. In the validation group, TNBC patients with DNA repair gene mutations achieved 77.8% pCR.

Conclusions: A subset of TNBC patients carry deleterious somatic mutations in 10 HR-related genes. The mutation status of this expanded gene panel is likely to effectively predict respond rate to neoadjuvant chemotherapy based on paclitaxel and carboplatin. Our findings need to be validated through follow-up studies in this and additional cohorts.
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http://dx.doi.org/10.21037/atm-20-4852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944335PMC
February 2021

A Fluorescent Metal-Organic Framework for Food Real-Time Visual Monitoring.

Adv Mater 2021 Apr 10;33(15):e2008020. Epub 2021 Mar 10.

Department of Chemistry, University of Texas at San Antonio, San Antonio, TX, 78249, USA.

Due to increasing food-safety issues, exploiting efficient approaches for food quality assessment and instrumentation has attracted concerns worldwide. Herein, a smart evaluation system based on a fluorescent metal-organic framework (MOF) is developed for real-time visual monitoring of food freshness. Via post-synthetic modification, a ratiometric fluorescent MOF probe is constructed by covalently coupling fluorescein 5-isothiocyanate (5-FITC) with NH -rich lanthanide MOF. The probes exhibit a dual-emissive-responsive to biogenic amine, resulting in an increase in FITC emission along with a decrease in Eu emission accompanied by a clear distinguishable color transition from orange red to green. After doping the probes on a flexible substrate, the obtained MOF composite film can be integrated with a smartphone-based portable platform easily. It is proved that this smart evaluation system can be used for on-site inspection of the freshness of raw fish samples. This work develops a fluorescent MOF-based smart evaluation system as a novel platform for application in food monitoring, which not only has enormous economic value but also holds great public health significance.
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http://dx.doi.org/10.1002/adma.202008020DOI Listing
April 2021

Facilely Cross-Linking Polybenzimidazole with Polycarboxylic Acids to Improve H/CO Separation Performance.

ACS Appl Mater Interfaces 2021 Mar 8;13(10):12521-12530. Epub 2021 Mar 8.

Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, New York 14260, United States.

Polybenzimidazole (PBI) with a strong size-sieving ability exhibits attractive H/CO separation properties for blue H production and CO capture. Herein, we report that PBI can be facilely cross-linked with polycarboxylic acids, oxalic acid (OA), and -aconitic acid (TaA) to improve its separation performance. The acids react with the amines on the PBI chains, decreasing free volume and increasing size-sieving ability. The acid doping increases H/CO selectivity from 12 to as high as 45 at 35 °C. The acid-doped samples demonstrate stable H/CO separation performance when challenged with simulated syngas containing water vapor at 150 °C, which surpasses state-of-the-art polymers and Robeson's upper bound for H/CO separation.
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http://dx.doi.org/10.1021/acsami.0c23098DOI Listing
March 2021