Publications by authors named "Junchao Wang"

40 Publications

Characterization of MW06, a human monoclonal antibody with cross-neutralization activity against both SARS-CoV-2 and SARS-CoV.

MAbs 2021 Jan-Dec;13(1):1953683

Department of Antibody Discovery and Development, Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China.

The global pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in widespread social and economic disruption. Effective interventions are urgently needed for the prevention and treatment of COVID-19. Neutralizing monoclonal antibodies (mAbs) have demonstrated their prophylactic and therapeutic efficacy against SARS-CoV-2, and several have been granted authorization for emergency use. Here, we discover and characterize a fully human cross-reactive mAb, MW06, which binds to both SARS-CoV-2 and SARS-CoV spike receptor-binding domain (RBD) and disrupts their interaction with angiotensin-converting enzyme 2 (ACE2) receptors. Potential neutralization activity of MW06 was observed against both SARS-CoV-2 and SARS-CoV in different assays. The complex structure determination and epitope alignment of SARS-CoV-2 RBD/MW06 revealed that the epitope recognized by MW06 is highly conserved among SARS-related coronavirus strains, indicating the potential broad neutralization activity of MW06. In assays, no antibody-dependent enhancement (ADE) of SARS-CoV-2 infection was observed for MW06. In addition, MW06 recognizes a different epitope from MW05, which shows high neutralization activity and has been in a Phase 2 clinical trial, supporting the development of the cocktail of MW05 and MW06 to prevent against future escaping variants. MW06 alone and the cocktail show good effects in preventing escape mutations, including a series of variants of concern, B.1.1.7, P.1, B.1.351, and B.1.617.1. These findings suggest that MW06 recognizes a conserved epitope on SARS-CoV-2, which provides insights for the development of a universal antibody-based therapy against SARS-related coronavirus and emerging variant strains, and may be an effective anti-SARS-CoV-2 agent.
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http://dx.doi.org/10.1080/19420862.2021.1953683DOI Listing
July 2021

The outer membrane protein Amuc_1100 of Akkermansia muciniphila alleviates the depression-like behavior of depressed mice induced by chronic stress.

Biochem Biophys Res Commun 2021 Aug 12;566:170-176. Epub 2021 Jun 12.

School of Life Sciences, Anhui University, Hefei, Anhui, 230601, China; Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, Anhui, 230601, China. Electronic address:

Akkermansia muciniphila is a symbiotic intestinal bacterium with a high medicinal value. Amuc_1100 is the outer membrane protein of A. muciniphila and plays an important role in the interaction between A. muciniphila and its host. The objective of this study was to evaluate the antidepressant activity of Amuc_1100 in a chronic unpredictable mild stress (CUMS) model. Amuc_1100 intervention ameliorated CUMS-induced depression-like behavior and CUMS-induced down-regulation of serotonin (5-hydroxytryptamine, or simply, 5-HT) in the serum and colon of mice. Microbial analysis of mouse feces showed that Amuc_1100 could improve the gut microbiota dysregulation induced by CUMS. In addition, Amuc_1100 intervention could also improve the down-regulation of brain-derived neurotrophic factor (BDNF) and inflammation in the hippocampus induced by CUMS. These results suggest that Amuc_1100 has a good antidepressant effect, and the mechanism may be related to the improvement of gut microbiota, the up-regulation of the BDNF level, and the inhibition of the neuroinflammatory response.
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http://dx.doi.org/10.1016/j.bbrc.2021.06.018DOI Listing
August 2021

The outer membrane protein Amuc_1100 of promotes intestinal 5-HT biosynthesis and extracellular availability through TLR2 signalling.

Food Funct 2021 Apr;12(8):3597-3610

School of Life Sciences, Anhui University, Hefei 230601, Anhui, China. and Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei 230601, Anhui, China.

Akkermansia muciniphila is a probiotic inhabiting host intestinal mucus layers and displays evident easing or therapeutic effects on host enteritis and metabolic disorders such as obesity and diabetes. The outer membrane protein Amuc_1100 of A. muciniphila is likely to play a crucial role during the interaction with the host. 5-HT is a neurotransmitter and a key signal molecule regulating the gastrointestinal tract functions and other organs, which is involved in diverse physiological and pathological processes. This study demonstrated that Amuc_1100 could promote the expression of the 5-HT synthesis rate-limiting enzyme Tph1 in RIN-14B cells and reduce the expression of the serotonin reuptake transporter (SERT) in Caco-2 cells through direct interaction with TLR2, thereby improving 5-HT biosynthesis and extracellular availability. Using antibiotic-treated mice as animal models, we found that after gavage with A. muciniphila or Amuc_1100, Tph1 expression increased and SERT expression decreased in colon tissues. The 5-HT concentrations in colon tissues and blood were markedly elevated simultaneously. We also found that A. muciniphila or Amuc_1100 improved the gastrointestinal motility function and restored gut microbiota abundance and species diversity in antibiotic-treated mice. These results suggest that A. muciniphila can regulate the host intestinal 5-HT system via its outer membrane protein Amuc_1100 and TLR2. This mechanism represented an important approach through which A. muciniphila interacts with the host and further influences 5-HT-related physiological functions. These results advance the understanding of interplay mechanisms between the gut microbiota and the host, which could be the basis for new intervention strategies for related diseases.
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http://dx.doi.org/10.1039/d1fo00115aDOI Listing
April 2021

Automated calibration of 3D-printed microfluidic devices based on computer vision.

Biomicrofluidics 2021 Mar 10;15(2):024102. Epub 2021 Mar 10.

Key Laboratory of RF Circuits and Systems, Ministry of Education, Hangzhou Dianzi University, Hangzhou 310018, China.

With the development of 3D printing techniques, the application of it in microfluidic/Lab-on-a-Chip (LoC) fabrication is becoming more and more attractive. However, to achieve a satisfying printing quality of the target devices, researchers usually require quite an amount of work in calibration trials even for high-end 3D printers. To increase the calibration efficiency of the average priced printers and promote the application of 3D printing technology in the microfluidic community, this work has presented a computer vision (CV)-based method for rapid and precise 3D printing calibration with examples on cylindrical hole/post diameters of 0.2-2.4 mm and rectangular hole/post widths of 0.2-1.0 mm by a stereolithography-based 3D printer. Our method is fully automated, which contains five steps and only needs a camera at hand to provide photos for convolutional neural network recognition. The experimental results showed that our CV-based method could provide calibrated dimensions with just one print of the specific calibration ruler to meet user desire. The higher resolution of the photo provides a higher precision in calibration. Subsequently, only one more print for the target device is needed after the calibration process. Overall, this work has provided a quick and precise calibration tool for researchers to apply 3D printing in the fabrication of their microfluidic/LoC devices with average price printers. Besides, with our open source calibration software and calibration ruler design file, researchers can modify the specific setting based on customized needs and conduct calibration on any type of 3D printer.
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http://dx.doi.org/10.1063/5.0037274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952140PMC
March 2021

Structural insights into the intermolecular interaction of the adhesin SdrC in the pathogenicity of Staphylococcus aureus.

Acta Crystallogr F Struct Biol Commun 2021 Feb 2;77(Pt 2):47-53. Epub 2021 Feb 2.

School of Life Sciences, Anhui University, 111 Jiulong Road, Hefei, Anhui 230601, People's Republic of China.

Staphylococcus aureus is an opportunistic disease-causing pathogen that is widely found in the community and on medical equipment. A series of virulence factors secreted by S. aureus can trigger severe diseases such as sepsis, endocarditis and toxic shock, and thus have a great impact on human health. The transformation of S. aureus from a colonization state to a pathogenic state during its life cycle is intimately associated with the initiation of bacterial aggregation and biofilm accumulation. SdrC, an S. aureus surface protein, can act as an adhesin to promote cell attachment and aggregation by an unknown mechanism. Here, structural studies demonstrate that SdrC forms a unique dimer through intermolecular interaction. It is proposed that the dimerization of SdrC enhances the efficiency of bacteria-host attachment and therefore contributes to the pathogenicity of S. aureus.
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http://dx.doi.org/10.1107/S2053230X21000741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900927PMC
February 2021

Continuous Paravertebral Analgesia versus Continuous Epidural Analgesia after Video-Assisted Thoracoscopic Lobectomy for Lung Cancer: A Randomized Controlled Trial.

Ann Thorac Cardiovasc Surg 2021 Feb 16. Epub 2021 Feb 16.

Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.

Background: Whether continuous thoracic epidural analgesia (TEA) and continuous paravertebral block (PVB) have similar analgesic effects in patients undergoing video-assisted thoracic surgery (VATS) lobectomy was compared in this study.

Methods: In all, 86 patients undergoing VATS lobectomy were enrolled in the prospective, randomized clinical trial. Group E received TEA. Group P received PVB. The primary endpoint was postoperative 24-hour visual rating scale (VAS) on coughing. Side effects and postoperative complications were also analyzed.

Results: Pain scores at rest or on coughing at 24 and 48 h postoperatively were significantly lower in group E than in group P (P <0.05). At 24 h postoperatively, more patients in group E suffered from vomiting (32.6% vs 11.6%, P = 0.019), dizziness (55.8% vs 12.9%, P = 0.009), pruritus (27.9% vs 2.3%, P = 0.002), and hypotension (32.6% vs 4.7%, P = 0.002) than those in group P. Patients in group E were more satisfied (P = 0.047). Four patients in group P and two patients in group E suffered from pulmonary complications (P >0.05). The length of hospital and intensive care unit (ICU) stays were not significantly different.

Conclusions: Though TEA has more adverse events than PVB, it may be superior to PVB in patients undergoing VATS lobectomy.
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http://dx.doi.org/10.5761/atcs.oa.20-00283DOI Listing
February 2021

Amuc_1102 from Akkermansia muciniphila adopts an immunoglobulin-like fold related to archaeal type IV pilus.

Biochem Biophys Res Commun 2021 Apr 14;547:59-64. Epub 2021 Feb 14.

School of Life Sciences, Anhui University, Hefei, Anhui, 230601, China; Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, Anhui, 230601, China; Institute of Physical Science, Institute of Information Technology, Anhui University, Hefei, Anhui, 230601, China. Electronic address:

Akkermansia muciniphila is a kind of beneficial microorganism colonized in the human gut. A. muciniphila is closely related to human intestinal health and has a good effect on diseases related to intestinal metabolism. The proteins encoded by the Amuc_1098-Amuc_1102 gene cluster, which are related to the formation and assembly of the pilus, are highly expressed in the membrane protein components of A. muciniphila. In this paper, we report the crystal structure of Amuc_1102 at a resolution of 1.75 Å, which adopts an immunoglobulin (Ig)-like fold. Amuc_1102 shares a similar fold to three archaeal proteins related to type IV pilus (T4P)-like structure, Pilin, FlaF, and FlaG, indicating a similar function. Amuc_1102 exists as a trimer both in the crystal structure and in solution, which differs from the assemblies of Pilin, FlaF, and FlaG. This study provides a structural basis for the elucidation of the T4P formation of A. muciniphila.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.022DOI Listing
April 2021

Structural basis for RNA recognition by the N-terminal tandem RRM domains of human RBM45.

Nucleic Acids Res 2021 03;49(5):2946-2958

Institutes of Physical Science and Information Technology, Anhui University, 111 Jiulong Road, Hefei 230601, Anhui, China.

RBM45 is an RNA-binding protein involved in neural development, whose aggregation is associated with neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD). However, the mechanisms of RNA-binding and aggregation of RBM45 remain unelucidated. Here, we report the crystal structure of the N-terminal tandem RRM domains of human RBM45 in complex with single-stranded DNA (ssDNA). Our structural and biochemical results revealed that both the RRM1 and RRM2 of RBM45 recognized the GAC sequence of RNA/ssDNA. Two aromatic residues and an arginine residue in each RRM were critical for RNA-binding, and the interdomain linker was also involved in RNA-binding. Two RRMs formed a pair of antiparallel RNA-binding sites, indicating that the N-terminal tandem RRM domains of RBM45 bound separate GAC motifs in one RNA strand or GAC motifs in different RNA strands. Our findings will be helpful in the identification of physiologic targets of RBM45 and provide evidence for understanding the physiologic and pathologic functions of RBM45.
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http://dx.doi.org/10.1093/nar/gkab075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968997PMC
March 2021

Predicting the fluid behavior of random microfluidic mixers using convolutional neural networks.

Lab Chip 2021 01 16;21(2):296-309. Epub 2020 Dec 16.

Key Laboratory of RF Circuits and Systems, Ministry of Education, and, Zhejiang Provincial Laboratory of Integrated Circuit Design, Hangzhou Dianzi University, China.

With the various applications of microfluidics, numerical simulation is highly recommended to verify its performance and reveal potential defects before fabrication. Among all the simulation parameters and simulation tools, the velocity field and concentration profile are the key parts and are generally simulated using finite element analysis (FEA). In our previous work [Wang et al., Lab Chip, 2016, 21, 4212-4219], automated design of microfluidic mixers by pre-generating a random library with the FEA was proposed. However, the duration of the simulation process is time-consuming, while the matching consistency between limited pre-generated designs and user desire is not stable. To address these issues, we inventively transformed the fluid mechanics problem into an image recognition problem and presented a convolutional neural network (CNN)-based technique to predict the fluid behavior of random microfluidic mixers. The pre-generated 10 513 candidate designs in the random library were used in the training process of the CNN, and then 30 757 brand new microfluidic mixer designs were randomly generated, whose performance was predicted by the CNN. Experimental results showed that the CNN method could complete all the predictions in just 10 seconds, which was around 51 600× faster than the previous FEA method. The CNN library was extended to contain 41 270 candidate designs, which has filled up those empty spaces in the fluid velocity versus solute concentration map of the random library, and able to provide more choices and possibilities for user desire. Besides, the quantitative analysis has confirmed the increased compatibility of the CNN library with user desire. In summary, our CNN method not only presents a much faster way of generating a more complete library with candidate mixer designs but also provides a solution for predicting fluid behavior using a machine learning technique.
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http://dx.doi.org/10.1039/d0lc01158dDOI Listing
January 2021

The Postoperative Analgesic Effect of Ultrasound-Guided Bilateral Transversus Abdominis Plane Combined with Rectus Sheath Blocks in Laparoscopic Hepatectomy: A Randomized Controlled Study.

Ther Clin Risk Manag 2020 18;16:881-888. Epub 2020 Sep 18.

Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.

Background: Our aim was to investigate the postoperative analgesic effect of ultrasound (US)-guided bilateral transversus abdominis plane (TAP) blocks combined with rectus sheath blocks (RSBs) in laparoscopic hepatectomy.

Patients And Methods: A total of 126 patients were allocated into two groups for analysis. Group 1 (n = 63) did not receive any local anesthetics. Group 2 (n = 63) received US-guided bilateral TAP blocks and RSBs using 20 mL 0.25% ropivacaine in each block. Postoperative pain scores, the dose of intraoperative remifentanil, 24 h consumption of oxycodone, adverse events such as postoperative dizziness, nausea and vomiting, and the length of postoperative hospital stay were recorded.

Results: In the postanesthesia care unit, patients in group 2 had significantly lower pain visual analog scale (VAS) scores at rest than those in group 1 ( < 0.001). The VAS scores both at rest and during movement were significantly lower in group 2 than in group 1 at 2, 4 and 6 h postoperatively (all < 0.001). There was no difference in VAS scores between the two groups at rest 24 h postoperatively ( = 0.477). However, the VAS score during movement at 24 h in group 2 was significantly lower than that in group 1 ( < 0.001). No significant differences in the incidence of adverse events or the dose of intraoperative remifentanil were observed between the two groups (all > 0.05). Patients in group 2 had a significantly lower 24 h consumption of oxycodone than patients in group 1 ( < 0.001). The mean length of postoperative hospital stay of group 2 was shorter than that of group 1 ( = 0.032).

Conclusion: US-guided bilateral TAP blocks combined with RSBs provide effective postoperative analgesia for laparoscopic hepatectomy, and they could shorten the postoperative hospital stay without increasing the incidence of adverse events from opioids.
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http://dx.doi.org/10.2147/TCRM.S267735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509310PMC
September 2020

Universal Triboelectric Nanogenerator Simulation Based on Dynamic Finite Element Method Model.

Sensors (Basel) 2020 Aug 27;20(17). Epub 2020 Aug 27.

Ministry of Education Key Lab of RF Circuits and Systems, College of Electronics & Information, Hangzhou Dianzi University, Hangzhou 310000, China.

The lack of a universal simulation method for triboelectric nanogenerator (TENG) makes the device design and optimization difficult before experiment, which protracts the research and development process and hinders the landing of practical TENG applications. The existing electrostatic induction models for TENGs have limitations in simulating TENGs with complex geometries and their dynamic behaviors under practical movements due to the topology change issues. Here, a dynamic finite element method (FEM) model is proposed. The introduction of air buffer layers and the moving mesh method eliminates the topology change issues during practical movement and allows simulation of dynamic and time-varying behaviors of TENGs with complex 2D/3D geometries. Systematic investigations are carried out to optimize the air buffer thickness and mesh densities, and the optimized results show excellent consistency with the experimental data and results based on other existing methods. It also shows that a 3D disk-type rotating TENG can be simulated using the model, clearly demonstrating the capability and superiority of the dynamic FEM model. Moreover, the dynamic FEM model is used to optimize the shape of the tribo-material, which is used as a preliminary example to demonstrate the possibility of designing a TENG-based sensor.
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http://dx.doi.org/10.3390/s20174838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506595PMC
August 2020

The variable oligomeric state of Amuc_1100 from Akkermansia muciniphila.

J Struct Biol 2020 10 28;212(1):107593. Epub 2020 Jul 28.

School of Life Sciences, Anhui University, Hefei 230601, Anhui, China; Institutes of Physical Science and Information Technology, Anhui University, Hefei 230601, Anhui, China; Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei 230601, Anhui, China. Electronic address:

Akkermansia muciniphila is a beneficial microorganism colonized in the human gut that can reverse many intestinal metabolic-related diseases. Amuc_1100 is an outer-membrane protein of A. muciniphila. Oral administration of Amuc_1100 can reduce fat mass development, insulin resistance, and dyslipidemia in mice and activated the toll-like receptor 2 (TLR2) to regulate the immune response of the host, but the molecular mechanism remains unclear. Here we report the crystal structure of the extramembranous domain of Amuc_1100, which consists of a four-stranded antiparallel β-sheet and four α-helices. Two C-terminal helices and the four-stranded antiparallel β-sheet formed two "αββ" motifs and constituted the core domain, which shared a similar fold with type IV pili and type II Secretion system protein. Although the full-length of the extramembranous domain of Amuc_1100 existed as a monomer in solution, they formed trimer in the crystal. Elimination of the N-terminal coiled-coil helix α1 led to dimerization of Amuc_1100 both in solution and in crystal, indicating that the oligomeric state of Amuc_1100 was variable and could be influenced by α1. In addition, we identified that Amuc_1100 could directly bind human TLR2 (hTRL2) in vitro, suggesting that Amuc_1100 may serve as a new ligand for hTLR2. Dimerization of Amuc_1100 improved its hTLR2-binding affinity, suggesting that the α1-truncated Amuc_1100 could be a beneficial candidate for the development of A. muciniphila related drugs.
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http://dx.doi.org/10.1016/j.jsb.2020.107593DOI Listing
October 2020

Structural insights into the fungi-nematodes interaction mediated by fucose-specific lectin AofleA from Arthrobotrys oligospora.

Int J Biol Macromol 2020 Dec 19;164:783-793. Epub 2020 Jul 19.

School of Life Sciences, Anhui University, Hefei 230601, Anhui, China; Institutes of Physical Science and Information Technology, Anhui University, Hefei 230601, Anhui, China; Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei 230601, Anhui, China. Electronic address:

Fungal lectin can bind specific carbohydrate structures of the host and work in recognition and adhesion or as a toxic factor. AofleA, as a fucose-specific lectin from widely studied nematode predatory fungus Arthrobotrys oligospora, possibly plays a key role in the event of capturing nematodes, but the mechanism remains unknown. Here we report the crystal structure of AofleA, which exists as a homodimer with each subunit folds as a six-bladed β-propeller. Our structural and biological results revealed that three of the six putative binding sites of AofleA had fucose-binding abilities. In addition, we found that AofleA could bind to the pharynx and intestine of the nematode in a fucose-binding-dependent manner. Our results facilitate the understanding of the mechanism that fucose-specific lectin mediates fungi-nematodes interaction, and provide structural information for the development of potential applications of AofleA.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.07.173DOI Listing
December 2020

Structural insight into the biological functions of Arabidopsis thaliana ACHT1.

Int J Biol Macromol 2020 May 3;158:43-51. Epub 2020 May 3.

School of Life Sciences, Anhui University, Hefei 230601, Anhui, China; Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei 230601, Anhui, China. Electronic address:

The Arabidopsis thaliana atypical Cys His-rich thioredoxins (ACHTs) are a small class of atypical thioredoxins (TRXs) located in chloroplasts thylakoids and are characterized by a noncanonical motif at their redox active site, C (G/S)(S/G)C. Previous studies have reported that ACHT1 can interact with A. thaliana 2-Cys peroxiredoxins (2-Cys Prxs, including PrxA and PrxB) to transmit oxidation signals in response to illumination with normal light intensity. In this study, we reported the crystal structure of ACHT1 and show that ACHT1 adopts a canonical TRX fold. Comparison of the structures of ACHT1 in both reducing and oxidizing environments revealed that while the redox environment did not influence the overall structure of ACHT1, it did change the conformation of its catalytic residues. We found that the catalytic C125 of ACHT1 is the target residue for PrxA in vitro. In addition, we found that ACHT1 can reduce the peroxidase activity of PrxA, and further confirmed that the ability of ACHT1 to restore the peroxidase function of PrxA was due to the interaction between the two. Our results provide a structural basis for studying the function of atypical TRXs and the oxidative regulation mechanism of ACHT1 and 2-Cys Prxs in chloroplasts.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.04.246DOI Listing
May 2020

Crystal structure of Akkermansia muciniphila peroxiredoxin reveals a novel regulatory mechanism of typical 2-Cys Prxs by a distinct loop.

FEBS Lett 2020 05 20;594(10):1550-1563. Epub 2020 Feb 20.

School of Life Sciences, Anhui University, Hefei, China.

Peroxiredoxins (Prxs) are thiol-specific antioxidant proteins commonly found in organisms that protect cells from the damage of reactive oxygen species produced by metabolism and that participate in cell signaling. The Prx from the bacterium Akkermansia muciniphila (AmPrx) is a typical 2-Cys Prx characterized by two conserved cysteines: Cys49 and Cys183. Here, we verified the peroxidase activity of AmPrx and determined its crystal structure in reduced form, which is a doughnut-shaped decamer composed of five dimers. Particularly, a distinct loop between the α4 helix and β6 strand is involved in the decameric interaction. Deletion of this loop destroys the decameric structure and significantly decreases the peroxidase activity of AmPrx. Our findings reveal a novel regulatory mechanism of typical 2-Cys Prx, in which the α4-β6 loop affects the assembly of Prx and, therefore, regulates its peroxidase activity.
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http://dx.doi.org/10.1002/1873-3468.13753DOI Listing
May 2020

Structural basis for mRNA recognition by human RBM38.

Biochem J 2020 01;477(1):161-172

School of Life Sciences, Anhui University, Hefei, Anhui 230601, China.

RNA-binding protein RBM38 was reported to bind the mRNA of several p53-related genes through its RRM domain and to up-regulate or down-regulate protein translation by increasing mRNA stability or recruitment of other effector proteins. The recognition mechanism, however, for RNA-binding of RBM38 remains unclear. Here, we report the crystal structure of the RRM domain of human RBM38 in complex with a single-stranded RNA. Our structural and biological results revealed that RBM38 recognizes G(U/C/A)GUG sequence single-stranded RNA in a sequence-specific and structure-specific manner. Two phenylalanine stacked with bases of RNA were crucial for RNA binding, and a series of hydrogen bonds between the base atoms of RNA and main-chain or side-chain atoms of RBM38 determine the sequence-specific recognition. Our results revealed the RNA-recognition mechanism of human RBM38 and provided structural information for understanding the RNA-binding property of RBM38.
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http://dx.doi.org/10.1042/BCJ20190652DOI Listing
January 2020

Identification of a monoclonal antibody that targets PD-1 in a manner requiring PD-1 Asn58 glycosylation.

Commun Biol 2019 25;2:392. Epub 2019 Oct 25.

1School of Life Sciences, Anhui University, 230601 Hefei, Anhui China.

Programmed cell death 1 (PD-1) is inhibitory receptor and immune checkpoint protein. Blocking the interaction of PD-1 and its ligands PD-L1/ L2 is able to active T-cell-mediated antitumor response. Monoclonal antibody-based drugs targeting PD-1 pathway have exhibited great promise in cancer therapy. Here we show that MW11-h317, an anti-PD-1 monoclonal antibody, displays high affinity for PD-1 and blocks PD-1 interactions with PD-L1/L2. MW11-h317 can effectively induce T-cell-mediated immune response and inhibit tumor growth in mouse model. Crystal structure of PD-1/MW11-h317 Fab complex reveals that both the loops and glycosylation of PD-1 are involved in recognition and binding, in which Asn58 glycosylation plays a critical role. The unique glycan epitope in PD-1 to MW11-h317 is different from the first two approved clinical PD-1 antibodies, nivolumab and pembrolizumab. These results suggest MW11-h317 as a therapeutic monoclonal antibody of PD-1 glycosylation-targeting which may become efficient alternative for cancer therapy.
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http://dx.doi.org/10.1038/s42003-019-0642-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814707PMC
April 2020

The crystal structure of sulfiredoxin from Arabidopsis thaliana revealed a more robust antioxidant mechanism in plants.

Biochem Biophys Res Commun 2019 12 8;520(2):347-352. Epub 2019 Oct 8.

School of Life Sciences, Anhui University, Hefei, Anhui, 230601, China; Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui, 230601, China; Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, Anhui, 230601, China. Electronic address:

Typical 2-cysteine peroxiredoxins (2-Cys Prxs) are critical peroxidase sensors and could be deactivated by the hyperoxidation under oxidative stress. In plants, 2-Cys Prxs present at a high level in chloroplasts and are repaired by Sulfiredoxin. Whereas many studies have explored the mechanism of Sulfiredoxin from Homo sapiens (HsSrx), the molecular mechanism of Sulfiredoxin in plants with unique photosynthesis remains unclear. Here we report the crystal structure of Sulfiredoxin from Arabidopsis thaliana (AtSrx), which displayed a typical ParB/Srx fold with an ATP bound at a conservative nucleotide binding motif GCHR. Both the ADP binding pocket and the putative AtSrx-AtPrxA interaction surface of AtSrx are more positively charged comparing to HsSrx, suggesting a robust mechanism of AtSrx. These features illustrate the unique mechanisms of AtSrx, which are vital for figure out the strategies of plants to cope with oxidation stress.
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http://dx.doi.org/10.1016/j.bbrc.2019.10.034DOI Listing
December 2019

Finding the optimal design of a passive microfluidic mixer.

Lab Chip 2019 11 2;19(21):3618-3627. Epub 2019 Oct 2.

Department of Bioengineering, University of California Riverside, Riverside, CA, USA.

The ability to thoroughly mix two fluids is a fundamental need in microfluidics. While a variety of different microfluidic mixers have been designed by researchers, it remains unknown which (if any) of these mixers are optimal (that is, which designs provide the most thorough mixing with the smallest possible fluidic resistance across the mixer). In this work, we automatically designed and rationally optimized a microfluidic mixer. We accomplished this by first generating a library of thousands of different randomly designed mixers, then using the non-dominated sorting genetic algorithm II (NSGA-II) to optimize the random chips in order to achieve Pareto efficiency. Pareto efficiency is a state of allocation of resources (e.g. driving force) from which it is impossible to reallocate so as to make any one individual criterion better off (e.g. pressure drop) without making at least one individual criterion (e.g. mixing performance) worse off. After 200 generations of evolution, Pareto efficiency was achieved and the Pareto-optimal front was found. We examined designs at the Pareto-optimal front and found several design criteria that enhance the mixing performance of a mixer while minimizing its fluidic resistance; these observations provide new criteria on how to design optimal microfluidic mixers. Additionally, we compared the designs from NSGA-II with some popular microfluidic mixer designs from the literature and found that designs from NSGA-II have lower fluidic resistance with similar mixing performance. As a proof of concept, we fabricated three mixer designs from 200 generations of evolution and one conventional popular mixer design and tested the performance of these four mixers. Using this approach, an optimal design of a passive microfluidic mixer is found and the criteria of designing a passive microfluidic mixer are established.
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http://dx.doi.org/10.1039/c9lc00546cDOI Listing
November 2019

MOF-derived manganese monoxide nanosheet-assembled microflowers for enhanced lithium-ion storage.

Nanoscale 2019 Jun;11(22):10763-10773

Center for Advanced Electric Energy Technologies (CAEET), School of Materials and Energy, University of Electronic Science and Technology of China, Chengdu 611731, P. R. China.

Achieving high energy density, power density and cycling performance is a great challenge for lithium-ion battery (LIB) anodes. To obtain favorable electrochemical properties, an effective approach for designing composite nanomaterials with good stability and large specific surface area has been reported here. In this work, metal-organic framework (MOF)-derived manganese monoxides with a stable macromolecular framework were synthesized by utilizing the template agent 1,2,3,4-butanetetracarboxylic acid (BTCA) and the organic salt manganese acetylacetone, which possess a compact microflower structure assembled by nanosheets. As a synergistic effect, not only the amorphous carbon derived from MOFs enhances the specific capacity and stability, but also the unique nanosheet exhibits a significant nano-effect and high areal capacity, which is in favour of an electrochemical reaction. For further enhancement of the electrochemical performance, reduced graphene oxide (rGO) was introduced. When tested as a LIB anode, the [email protected] composite displays superior reversible capacities (1716 mA h g-1 at 0.1 A g-1 and 930 mA h g-1 at 2 A g-1) and remarkable rate performances. The research results of the composite nanomaterials lay a foundation for the fabrication of high-capacity and stable anode materials in LIBs.
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http://dx.doi.org/10.1039/c9nr02206fDOI Listing
June 2019

Comparison  of  efficacy, safety, and costs between neoadjuvant hypofractionated radiotherapy and conventionally fractionated radiotherapy for esophageal carcinoma.

Cancer Med 2019 07 22;8(8):3710-3718. Epub 2019 May 22.

Sichuan Cancer Hospital and Institute, Chengdu, China.

Background: We compared the efficacy, safety, and costs of hypofractionated radiotherapy (HFRT) and conventional fractionated radiotherapy (CFRT) for the neoadjuvant treatment of esophageal cancer.

Materials And Methods: Overall, 110 patients with esophageal cancer treated with neoadjuvant chemoradiotherapy from October 2002 to July 2017 were retrospectively included and divided into a HFRT group (42 patients received 30 Gray [Gy]/10 fractions for 2 weeks) and a CFRT group [68 patients received 40 Gy/20 fractions for 4 weeks]. Concurrent chemotherapy comprised cisplatin combined with either 5-FU or taxane. Surgery was performed 3-8 weeks after radiotherapy. We compared the outcomes, adverse events, and costs between the two groups.

Results: Pathological downstaging was achieved in 78.6% of the HFRT group and 83.8% of the CFRT group (P = 0.612). Compared with the CFRT group, the HFRT group had similar pathological complete response (pCR) (33.3% vs 35.3%; P = 0.834), median overall survival (OS) (40.8 months vs 44.9 months; P = 0.772) and progression free survival (32.7 months vs 35.4 months; P = 0.785). The perioperative complication rates were also similar between the groups, but the treatment time and costs were significantly reduced in the HFRT group (P < 0.05). Finally, multivariate analysis identified cN0 stage, pathological downstaging and pCR as independent predictors of better OS.

Conclusion: Preoperative HFRT is effective and safe for esophageal cancer. Moreover, it is similar to CFRT in terms of overall survival and toxicity and is cost effective and less time consuming.
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http://dx.doi.org/10.1002/cam4.2250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639169PMC
July 2019

Improvement of cleaner composting production by adding Diatomite: From the nitrogen conservation and greenhouse gas emission.

Bioresour Technol 2019 Aug 24;286:121377. Epub 2019 Apr 24.

College of Natural Resources and Environment, Northwest A&F University, Yangling 712100, PR China. Electronic address:

In order to investigate the improvement of Diatomite (DM) on the production of cleaner composting, reflected by emission of NH and greenhouse gases (GHGs), three dosages of DM (0%, 5% and 10%) were added into mixture of pig manure and sawdust for 42 days composting. Addition of DM promoted the transformation of organic matter and improved the quality of end product. Meanwhile, it was confirmed by the increase of NO-N formation and nitrogen conservation. Besides, adding DM aided on reducing emission of CH, NO and NH by 18.27%-30.41%, 26.89%-84.16% and 10.41%-23.70%, respectively. Furthermore, the DM had a positive effect on the maturity of compost products, reflecting by GI value and HA/FA. Consequently, through the factor analysis, 10% was suggested to improve the quality of end product and reduce nitrogen loss as well as GHGs emission.
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http://dx.doi.org/10.1016/j.biortech.2019.121377DOI Listing
August 2019

Crystallographic evidence for substrate-assisted catalysis of β-N-acetylhexosaminidas from Akkermansia muciniphila.

Biochem Biophys Res Commun 2019 04 4;511(4):833-839. Epub 2019 Mar 4.

School of Life Sciences, Anhui University, 111 Jiulong Road, Hefei, Anhui, 230601, China; Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, 111 Jiulong Road, Hefei, Anhui, 230601, China. Electronic address:

β-N-acetylhexosaminidases from Akkermansia muciniphila was reported to perform the crystal structure with GlcNAc complex, which proved to be the substrate of Am2301. Domain II of Am2301 is consisted of amino acid residues 111-489 and is folded as a (β/α) barrel with the active site combined of the glycosyl hydrolases. Crystallographic evidence showed that Asp-278 and Glu-279 could be the catalytic site and Tyr-373 may plays a role on binding the substrate. Moreover, Am2301 prefers to bind Zn ion, which similar to other GH 20 family. Enzyme activity and kinetic parameters of wild-type Am2301 and mutants proved that Asp-278 and Glu-279 are the catalytic sites and they play a critical role on the catalytic process. Overall, our results demonstrate that Am2301 and its complex with GlcNAC provide obvious structural evidence for substrate-assisted catalysis. Obviously, this expands our understanding on the mode of substrate-assisted reaction for this enzyme family in Akkermansia muciniphila.
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http://dx.doi.org/10.1016/j.bbrc.2019.02.074DOI Listing
April 2019

An External-Catalyst-Free Trifluoromethylation/Cyclization Strategy To Access Trifluoromethylated-Dihydroisoquinolinones/Indolines with Togni Reagent II.

Org Lett 2019 03 6;21(6):1863-1867. Epub 2019 Mar 6.

College of Chemistry and Molecular Engineering , Zhengzhou University , Zhengzhou 450001 , China.

A novel and efficient CF radical-involved external-catalyst-free trifluoromethylation/cyclization methodology to access a group of new trifluoromethylated dihydroisoquinolinones was developed, by reacting different N-allylbenzamides with Togni-II in one pot under mild reaction conditions. Meanwhile, this external-catalyst-free trifluoromethylation/cyclization protocol was also well suitable for being employed to synthesize many valuable trifluoromethylated N-acetylindolines, by reacting N-aryl- N-allylacetamides with Togni-II. In both reactions, the amide groups of reactants themselves acted as the catalysts to promote the generation of the CF radical required for the following radical-cascade trifluoromethylation/cyclization reactions.
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http://dx.doi.org/10.1021/acs.orglett.9b00465DOI Listing
March 2019

Identification of DNA methylation module in seasonal allergic rhinitis.

Int J Pediatr Otorhinolaryngol 2019 Feb 29;117:163-166. Epub 2018 Nov 29.

Department of Otolaryngology, Qilu Hospital, Shandong Province, PR China.

Objective: In this study, we aimed to characterize the significant DNA methylation module of seasonal allergic rhinitis.

Methods: Methylation profiling E-GEOD-50222 was obtained from ArrayExpress database. Differential co-methylation network (DCN) was constructed based on the methylation data. From the DCN, we characterized multiple differential modules (M-DMs). Significant module was mapped to pathways to identify significant enriched pathways.

Results: At the criteria of absolute Pearson coefficient value > 0.8, the edges were chose to construct DCN. In the DCN, 16 seed genes were identified. Seed genes were used to construct M-DMs. After statistical analysis, one significant module with p < 0.05 were obtained. After pathways enrichment analysis, 17 significant pathways with p < 0.05 were obtained, and most of these pathways were associated with DNA replication.

Conclusion: One multiple differential module was identified in SAR, and seventeen significant pathways mapped by the module were identified as important factors in SAR. These results may provide new insights into the molecular mechanism of DNA methylation in SAR.
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http://dx.doi.org/10.1016/j.ijporl.2018.11.030DOI Listing
February 2019

A Software Defined Radio Evaluation Platform for WBAN Systems.

Sensors (Basel) 2018 Dec 19;18(12). Epub 2018 Dec 19.

Chongqing University of Posts and Telecommunications, Chongqing 400065, China.

In recent years, the Wireless Body Area Network (WBAN) concept has attracted significant academic and industrial attention. WBAN specifies a network dedicated to collecting personal biomedical data from advanced sensors that are then used for health and lifestyle purposes. In 2012, the 802.15.6 WBAN standard was released by the Institute of Electrical and Electronics Engineers (IEEE), which regulates and specifies the configurations of WBAN. Compared to the prevailing wireless communication technologies such as Bluetooth and ZigBee, the WBAN standard has the advantages of ultra-low power consumption, high reliability, and high-security protection while transmitting sensitive personal data. Based on the standard specification, several implementations have been published. However, in terms of evaluation, different designs were implemented in proprietary evaluation environments, which may lead to unfair comparison. In this paper, a Software-Defined Radio (SDR) evaluation platform for WBAN systems is proposed to evaluate the RF channel specified in the IEEE 802.15.6 standard. A narrowband communication protocol demonstration with a security scheme in WBAN has been performed to successfully validate the design in the proposed evaluation platform.
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http://dx.doi.org/10.3390/s18124494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6308829PMC
December 2018

A new species of subgenus Homoneura from Northern China, with information of 12 species newly recorded (Diptera: Lauxaniidae: Homoneura).

Zootaxa 2018 May 11;4418(6):501-525. Epub 2018 May 11.

College of Agronomy, Inner Mongolia Agricultural University, Hohhot 010019, China..

Homoneura (Homoneura) hanmaensis sp. nov. is described as new to science and 12 species are recorded from China for the first time: Homoneura (Homoneura) albomarginata Czerny, 1932, Homoneura (H.) biumbrata (Loew, 1847), Homoneura (H.) cerina Shatalkin, 2000, Homoneura (H.) euaresta (Coquillett, 1898), Homoneura (H.) filiola Czerny, 1932, Homoneura (H.) kaszabi Shewell, 1971, Homoneura (H.) lamellata (Becker, 1895), Homoneura (H.) mediospinosa Merz, 2003, Homoneura (H.) patella Shewell, 1971, Homoneura (H.) shewelliana Papp, 1978, Homoneura (H.) spinicauda Sasakawa and Ikeuchi, 1982, Homoneura (H.) tenera (Loew, 1846). A few of photographs and illustrations are provided for eight species. Keys are provided to separate eight species groups and Chinese species of eight species groups of subgenus Homoneura.
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http://dx.doi.org/10.11646/zootaxa.4418.6.1DOI Listing
May 2018

Crystal structure of Arabidopsis thaliana peroxiredoxin A C119S mutant.

Acta Crystallogr F Struct Biol Commun 2018 Oct 19;74(Pt 10):625-631. Epub 2018 Sep 19.

School of Life Sciences, Anhui University, 111 Jiulong Road, Hefei, Anhui 230601, People's Republic of China.

Peroxiredoxins (Prxs), a large family of antioxidant enzymes, are abundant in all living organisms. Peroxiredoxin A (PrxA) from Arabidopsis thaliana belongs to the typical 2-Cys Prx family and is localized in the chloroplast. This article reports the crystal structure of a PrxA C119S mutant refined to 2.6 Å resolution. The protein exists as a decamer both in the crystal structure and in solution. The structure is in the reduced state suitable for the approach of peroxide, though conformational changes are needed for the resolving process.
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http://dx.doi.org/10.1107/S2053230X18010920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168775PMC
October 2018

Silver-Catalyzed Radical Cascade Cyclization toward 1,5-/1,3-Dicarbonyl Heterocycles: An Atom-/Step-Economical Strategy Leading to Chromenopyridines and Isoxazole-/Pyrazole-Containing Chroman-4-Ones.

Org Lett 2018 10 25;20(19):6157-6160. Epub 2018 Sep 25.

Henan Joint International Research Laboratory of Green Construction of Functional Molecules and Their Bioanalytical Applications. College of Chemistry and Molecular Engineering , Zhengzhou University , Zhengzhou 450001 , China.

A novel and convenient silver-catalyzed radical cascade cyclization toward a large variety of 1,5-/1,3-dicarbonyl heterocycles containing a chroman-4-one, indanone, or 2,3-dihydroquinolin-4(1 H)-one moiety was developed, by reacting various 2-functionalized benzaldehydes, including 2-allyloxy benzaldehydes, 2-allyl benzaldehyde, and 2-N(Ts)CH-CH═CH substituted benzaldehyde, with 1,3-dicarbonyl compounds in the presence of AgNO/KSO in one pot under mild reaction conditions. The newly obtained 1,5-/1,3-dicarbonyl-containing heterocycles were further used directly to synthesize more structurally diverse polyheterocycles, mainly including chromenopyridines as well as isoxazole- or pyrazole-containing chroman-4-ones.
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http://dx.doi.org/10.1021/acs.orglett.8b02627DOI Listing
October 2018

Instantaneous simulation of fluids and particles in complex microfluidic devices.

PLoS One 2017 21;12(12):e0189429. Epub 2017 Dec 21.

Department of Bioengineering, University of California Riverside, Riverside, CA, United States of America.

Microfluidics researchers are increasingly using computer simulation in many different aspects of their research. However, these simulations are often computationally intensive: simulating the behavior of a simple microfluidic chip can take hours to complete on typical computing hardware, and even powerful workstations can lack the computational capabilities needed to simulate more complex chips. This slows the development of new microfluidic chips for new applications. To address this issue, we present a microfluidic simulation method that can simulate the behavior of fluids and particles in some typical microfluidic chips instantaneously (in around one second). Our method decomposes the chip into its primary components: channels and intersections. The behavior of fluid in each channel is determined by leveraging analogies with electronic circuits, and the behavior of fluid and particles in each intersection is determined by querying a database containing nearly 100,000 pre-simulated channel intersections. While constructing this database takes a nontrivial amount of computation time, once built, this database can be queried to determine the behavior of fluids and particles in a given intersection in a fraction of a second. Using this approach, the behavior of a microfluidic chip can be simulated in just one second on a standard laptop computer, without any noticeable degradation in the accuracy of the simulation. While our current technique has some constraints on the designs of the chips it can simulate (namely, T- or cross-shaped intersections, 90 degree channel turns, a fixed channel width, fluid flow rates between 0 and 2 cm/s, and particles with diameters between 1 and 20 microns), we provide several strategies for increasing the range of possible chip designs that can be simulated using our technique. As a proof of concept, we show that our simulation method can instantaneously simulate the paths followed by particles in both simple and complex microfluidic chips, with results that are essentially indistinguishable from simulations that took hours or even days to complete using conventional approaches.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0189429PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739417PMC
January 2018
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