Publications by authors named "Wenjun Zhang"

609 Publications

An unsupervised multi-scale framework with attention-based network (MANet) for lung 4D-CT registration.

Phys Med Biol 2021 Jun 14. Epub 2021 Jun 14.

Shandong Provincial Third Hospital, Jinan, Shandong, CHINA.

Deformable image registration (DIR) of 4D-CT is very important in many radiotherapeutic applications including tumor target definition, image fusion, dose accumulation and response evaluation. It is a challenging task to performing accurate and fast DIR of lung 4D-CT images due to its large and complicated deformations. In this study, we propose an unsupervised multi-scale DIR framework with attention-based network (MANet). Three cascaded models used for aligning CT images in different resolution levels were involved and trained by minimizing the loss functions, which were defined as the combination of dissimilarity between the fixed image and the deformed image and DVF regularization term. In addition, attention gates were incorporated into the three models to distinguish the moving structures from non-moving or minimal-moving structures during registration. The three models were trained sequentially and separately to minimize the loss function in each scale to initialize the MANet, and then trained jointly to minimize the total loss function which incorporated an additional dissimilarity between fixed image and deformed image. Besides, an adversarial network was integrated into MANet to enforce the DVF regularization by penalizing the unrealistic deformed images. The proposed MANet was evaluated on the public dir-lab dataset, and the target registration errors (TREs) of the model were compared with convention iterative optimization-based methods and three recently published deep learning-based methods. The initial results showed that the MANet with an average of TRE of 1.53±1.02 mm outperformed other registration methods, and its execution time took about 1 second for DVF estimation with no requirement of manual-tuning for parameters, which demonstrating that our proposed method had the ability of performing superior registration for 4D-CT.
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http://dx.doi.org/10.1088/1361-6560/ac0afcDOI Listing
June 2021

Soft-hard hybrid covalent-network polymer sponges with super resilience, recoverable energy dissipation and fatigue resistance under large deformation.

Mater Sci Eng C Mater Biol Appl 2021 Jul 14;126:112185. Epub 2021 May 14.

School of Mechatronics and Automation, Shanghai University, Shanghai, PR China; Division of Biomedical Engineering, University of Saskatchewan, Saskatoon, Canada.

Energy absorption or dissipation ability has been widely developed in tough hydrogels and 3D nano-structured sponges for a variety of applications. However, fully recoverable energy dissipation and fatigue resistance under large deformation is still challenging yet highly desirable. Polymer network with homogeneous chemical crosslinking structures is an efficient way to construct hydrogels with high resilience and fatigue resistance. Unfortunately, such polymer network usually has poor energy dissipation capability. In this paper, we propose a new approach to build the ability of fully recoverable energy dissipation into covalent-crosslink polymer network by integrating soft and hard chains in a uniform crosslinking network and present the one-pot synthesis method for constructing corresponding polymer sponges by low-temperature phase-separation photopolymerization. The application of such polymer sponges as a tissue engineering scaffold, fabricated by using cyclic acetal units and PEG based monomers in particular is demonstrated. For the first time, we show the feasibility of building a synthetic scaffold with the characteristics of high porosity, super compressibility and resilience, fast recovery, completely recoverable energy dissipation, high fatigue resistance, biodegradability and biocompatibility. Such a scaffold is promising in tissue engineering especially in load-bearing applications.
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http://dx.doi.org/10.1016/j.msec.2021.112185DOI Listing
July 2021

Organically-bound silicon enhances resistance to enzymatic degradation and nanomechanical properties of rice plant cell walls.

Carbohydr Polym 2021 Aug 30;266:118057. Epub 2021 Apr 30.

Institut für Mineralogie, University of Münster, 48149, Münster, Germany; School of Molecular and Life Science, Curtin University, 6845, Perth, Australia.

Plant cell walls exhibit excellent mechanical properties, which form the structural basis for sustainable bioresources and multifunctional nanocelluloses. The wall nanomechanical properties of living cells through covalent modifications of hybrid inorganic elements, such as silicon, may confer significant influence on local mechano-response and enzymatic degradation. Here, we present a combination of ex situ measurements of enzyme-released oligosaccharide fragments using MALDI-TOF MS and in situ atomic force microscopy (AFM) imaging through PeakForce quantitative nanomechanical mapping of tip-functionalized single-molecule enzyme-polysaccharide substrate recognition and the nanoscale dissolution kinetics of individual cellulose microfibrils of living rice (Oryza sativa) cells following silicate cross-linking of cell wall xyloglucan. We find that xyloglucan-bound silicon enhances the resistance to degradation by cellulase and improves the wall nanomechanical properties in the elastic modulus at the single-cell level. The findings establish a direct link between an inorganic element of silicon and the nanoscale architecture of plant cell wall materials for sustainable utilization.
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http://dx.doi.org/10.1016/j.carbpol.2021.118057DOI Listing
August 2021

Treatment Planning Optimization in Irreversible Electroporation for Complete Ablation of Variously Sized Cervical Tumors: A Numerical Study.

J Biomech Eng 2021 Jan;143(1)

Energy-Based Tumor Ablation Laboratory, School of Mechatronic Engineering and Automation, Shanghai University, Shanghai 200444, China.

Irreversible electroporation (IRE), a relatively new energy-based tumor ablation technology, has shown itself in the last decade to be able to safely ablate tumors with favorable clinical outcomes, yet little work has been done on optimizing the IRE protocol to variously sized tumors. Incomplete tumor ablation has been shown to be the main reason leading to the local recurrence and thus treatment failure. The goal of this study was to develop a general optimization approach to optimize the IRE protocol for cervical tumors in different sizes, while minimizing the damage to normal tissues. This kind of approach can lay a foundation for future personalized treatment of IRE. First, a statistical IRE cervical tumor death model was built using previous data in our group. Then, a multi-objective optimization problem model was built, in which the decision variables are five IRE-setting parameters, namely, the pulse strength (U), the length of active tip (H), the number of pulses delivered in one round between a pair of electrodes (A), the distance between electrodes (D), and the number of electrodes (N). The domains of the decision variables were determined based on the clinical experience. Finally, the problem model was solved by using nondominated sorting genetic algorithms II (NSGA-II) algorithm to give respective optimal protocol for three sizes of cervical tumors. Every protocol was assessed by the evaluation criterion established in the study to show the efficacy in a more straightforward way. The results of the study demonstrate this approach can theoretically provide the optimal IRE protocol for different sizes of tumors and may be generalizable to other types, sizes, and locations of tumors.
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http://dx.doi.org/10.1115/1.4047551DOI Listing
January 2021

Spurious North Tropical Atlantic precursors to El Niño.

Nat Commun 2021 05 25;12(1):3096. Epub 2021 May 25.

Institute for Basic Science, Center for Climate Physics, Busan, South Korea.

The El Niño-Southern Oscillation (ENSO), the primary driver of year-to-year global climate variability, is known to influence the North Tropical Atlantic (NTA) sea surface temperature (SST), especially during boreal spring season. Focusing on statistical lead-lag relationships, previous studies have proposed that interannual NTA SST variability can also feed back on ENSO in a predictable manner. However, these studies did not properly account for ENSO's autocorrelation and the fact that the SST in the Atlantic and Pacific, as well as their interaction are seasonally modulated. This can lead to misinterpretations of causality and the spurious identification of Atlantic precursors for ENSO. Revisiting this issue under consideration of seasonality, time-varying ENSO frequency, and greenhouse warming, we demonstrate that the cross-correlation characteristics between NTA SST and ENSO, are consistent with a one-way Pacific to Atlantic forcing, even though the interpretation of lead-lag relationships may suggest otherwise.
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http://dx.doi.org/10.1038/s41467-021-23411-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149707PMC
May 2021

Nonlinear modulation on optical trapping in a plasmonic bowtie structure.

Opt Express 2021 Apr;29(8):11664-11673

Surface plasmon optical tweezers based on micro- and nano-structures are capable of capturing particles in a very small spatial scale and have been widely used in many front research fields. In general, distribution of optical forces and potential wells exerted on the particles can be modulated by controlling the geometric parameters of the structures. However, these fabricated structures are irreversible once processed, which greatly limits its application in dynamic manipulation. The plasmonic field in these structures can be enhanced with orders of magnitude compared to the excitation light, offering a possibility to stimulate nonlinear responses as a new degree of freedom for dynamic modulation. Here, we theoretically demonstrate that the optical force and potential well can be modulated on account of the nonlinear Kerr effect of a gold bowtie structure under a pulsed laser with high peak power. The results verify that the trapping states, including the position, width, and depth of the potential well, can be dynamically modulated by changing intensity of the incident laser. It provides an effective approach for stable trapping and dynamic controlling of particles on nanostructure-based plasmonic trapping platforms and thus has great application potential in many fields, such as enhanced Raman detection, super-resolution imaging, and optical sensing.
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http://dx.doi.org/10.1364/OE.422493DOI Listing
April 2021

Self-assembly of Amphiphilic Porphyrins To Construct Nanoparticles for Highly Efficient Photodynamic Therapy.

Chemistry 2021 May 7. Epub 2021 May 7.

Key Laboratory of Photochemical Conversion and Optoelectronic Materials and CityU-CAS Joint Laboratory of Functional Materials and Devices Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

Hydrophobic photosensitizers greatly affect cell permeability and enrichment in tumors, but they cannot be used directly for clinical applications because they always aggregate in water, preventing their circulation in the blood and accumulation in tumor cells. As a result, amphiphilic photosensitizers are highly desirable. Although nanomaterial-based photosensitizers can solve water solubility, they have the disadvantages of complicated operation, poor reproducibility, low drug loading, and poor stability. In this work, an efficient synthesis strategy is proposed that converts small molecules into nanoparticles in 100 % aqueous solution by molecular assembly without the addition of any foreign species. Three photosensitizers with triphenylphosphine units and ethylene glycol chains of different lengths, TPP-PPh , TPP-PPh -2PEG and TPP-PPh -4PEG, were synthesized to improve amphiphilicity. Of the three photosensitizers, TPP-PPh -4PEG is the most efficient (singlet oxygen yield: 0.89) for tumor photodynamic therapy not only because of its definite constituent, but also because its amphiphilic structure allows it to self-assemble in water.
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http://dx.doi.org/10.1002/chem.202101199DOI Listing
May 2021

Small molecule natural products in human nasal/oral microbiota.

J Ind Microbiol Biotechnol 2021 Jun;48(3-4)

Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley 94720, USA.

Small molecule natural products are a chemically diverse class of biomolecules that fulfill myriad biological functions, including autoregulation, communication with microbial neighbors and the host, interference competition, nutrient acquisition, and resistance to oxidative stress. Human commensal bacteria are increasingly recognized as a potential source of new natural products, which may provide insight into the molecular ecology of many different human body sites as well as novel scaffolds for therapeutic development. Here, we review the scientific literature on natural products derived from residents of the human nasal/oral cavity, discuss their discovery, biosynthesis, and ecological roles, and identify key questions in the study of these compounds.
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http://dx.doi.org/10.1093/jimb/kuab010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210680PMC
June 2021

Slot-die coating large-area formamidinium-cesium perovskite film for efficient and stable parallel solar module.

Sci Adv 2021 Apr 30;7(18). Epub 2021 Apr 30.

Wuhan National Laboratory for Optoelectronics (WNLO), Huazhong University of Science and Technology (HUST), Wuhan 430074, China.

Perovskite solar cells have emerged as one of the most promising thin-film photovoltaic (PV) technologies and have made a strong debut in the PV field. However, they still face difficulties with up-scaling to module-level devices and long-term stability issue. Here, we report the use of a room-temperature nonvolatile Lewis base additive, diphenyl sulfoxide(DPSO), in formamidinium-cesium (FACs) perovskite precursor solution to enhance the nucleation barrier and stabilize the wet precursor film for the scalable fabrication of uniform, large-area FACs perovskite films. With a parallel-interconnected module design, the resultant solar module realized a certified quasi-stabilized efficiency of 16.63% with an active area of 20.77 cm The encapsulated modules maintained 97 and 95% of their initial efficiencies after 10,000 and 1187 hours under day/night cycling and 1-sun equivalent white-light light-emitting diode array illumination with maximum power point tracking at 50°C, respectively.
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http://dx.doi.org/10.1126/sciadv.abg3749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087413PMC
April 2021

Personal Neoantigens From Patients With NSCLC Induce Efficient Antitumor Responses.

Front Oncol 2021 13;11:628456. Epub 2021 Apr 13.

Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Tongji University, Shanghai, China.

Objective: To develop a neoantigen-targeted personalized cancer treatment for non-small cell lung cancer (NSCLC), neoantigens were obtained from collected human lung cancer samples, and the utility of neoantigen and neoantigen-reactive T cells (NRTs) was assessed.

Methods: Tumor specimens from three patients with NSCLC were obtained and analyzed by whole-exome sequencing, and neoantigens were predicted accordingly. Dendritic cells and T lymphocytes were isolated, NRTs were elicited and IFN-γ ELISPOT tests were conducted. HLA-A2.1/K transgenic mice were immunized with peptides from HLA-A*02:01patient with high immunogenicity, and NRTs were subjected to IFN-γ, IL-2 and TNF-α ELISPOT as well as time-resolved fluorescence assay for cytotoxicity assays to verify the immunogenicity . The HLA-A*02:01lung cancer cell line was transfected with minigene and inoculated into the flanks of C57BL/6 mice and the NRTs induced by the immunogenic polypeptides from autologous HLA-A2.1/K transgenic mice were adoptively transfused to verify their immunogenicity .

Results: Multiple putative mutation-associated neoantigens with strong affinity for HLA were selected from each patient. Immunogenic neoantigen were identified in all three NSCLC patients, the potency of ACAD8-T105I, BCAR1-G23V and PLCG1-M425L as effective neoantigen to active T cells in suppressing tumor growth was further proven both and using HLA-A2.1/Kb transgenic mice and tumor-bearing mouse models.

Conclusion: Neoantigens with strong immunogenicity can be screened from NSCLC patients through the whole-exome sequencing of patient specimens and machine-learning-based neoantigen predictions. NRTs shown efficient antitumor responses in transgenic mice and tumor-bearing mouse models. Our results indicate that the development of neoantigen-based personalized immunotherapies in NSCLC is possible.

Precis: Neoantigens with strong immunogenicity were screened from NSCLC patients. This research provides evidence suggesting that neoantigen-based therapy might serve as feasible treatment for NSCLC.
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http://dx.doi.org/10.3389/fonc.2021.628456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076796PMC
April 2021

Discovery of a new asymmetric dimer nenestatin B and implications of a dimerizing enzyme in a deep sea actinomycete.

Org Biomol Chem 2021 May 22;19(19):4243-4247. Epub 2021 Apr 22.

Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Innovation Academy of South China Sea Ecology and Environmental Engineering, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.

Benzofluorene-containing atypical angucyclines are an important family of natural products with a broad spectrum of antibacterial and cytotoxic properties. Interestingly, symmetric and asymmetric dimers showed better activity than the monomer in this class of compounds. Herein, we reported the isolation of a new asymmetric dimer nenestatin B (2) from the deep sea actinomycete Micromonospora echinospora SCSIO 04089 and a monomer nenestatin C (3) from an NmrA family regulatory protein coding gene nes18 inactivated mutant. The structural elucidation of 3 indicated the essential role of Nes18 in the biosynthetic pathway of 2, specifically in dimerization via C-C bond formation.
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http://dx.doi.org/10.1039/d1ob00310kDOI Listing
May 2021

Ultrasound-Enhanced Self-Exciting Photodynamic Therapy Based on Hypocrellin B.

Chem Asian J 2021 May 21;16(10):1221-1224. Epub 2021 Apr 21.

Key Laboratory of Photochemical Conversion and Optoelectronic Materials and CityU-CAS Joint Laboratory of Functional Materials and Devices, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

Peroxalate CL as an energy source to excite photosensitizers has attracted tremendous attention in photodynamic therapy (PDT). In this work, peroxyoxalate CPPO and hypocrellin B (HB)-based nanoparticles (CBNPs) for ultrasound (US)-enhanced self-exciting PDT were designed and prepared. CBNPs showed an excellent therapeutic effect against cancer cells with the assistance of US. This US-enhanced-chemiluminescence system avoids the dependence on external light and provides an example for inspiring more effective and precise strategies for cancer treatment.
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http://dx.doi.org/10.1002/asia.202100205DOI Listing
May 2021

An study of a custom-made high-frequency irreversible electroporation generator on different tissues for clinically relevant ablation zones.

Int J Hyperthermia 2021 ;38(1):593-603

Division of Biomedical Engineering, University of Saskatchewan, Saskatoon, Canada.

Purpose: To examine the ablation zone, muscle contractions, and temperature increases in both rabbit liver and kidney models for a custom-made high-frequency irreversible electroporation (H-FIRE) generator.

Materials And Methods: A total of 18 New Zealand white rabbits were used to investigate five H-FIRE protocols ( = 3 for each protocol) and an IRE protocol ( = 3) for the performance of the designed H-FIRE device in both liver and kidney tissues. The ablation zone was determined by using histological analysis 72 h after treatment. The extent of muscle contractions and temperature change during the application of pulse energy were measured by a commercial accelerometer attached to animals and fiber optic temperature probe inserted into organs with IRE electrodes, respectively.

Results: All H-FIRE protocols were able to generate visible ablation zones without muscle contractions, for both liver and kidney tissues. The area of ablation zone generated in H-FIRE pulse protocols (e.g., 0.3-1 μs, 2000 V, and 90-195 bursts) appears similar to that of IRE protocol (100 μs, 1000 V, and 90 pulses) in both liver and kidney tissues. No significant temperature increase was noticed except for the protocol with the highest pulse energy (e.g., 1 μs, 2000 V, and 180 bursts).

Conclusion: Our work serves to complement the current H-FIRE pulse waveforms, which can be optimized to significantly improve the quality of ablation zone in terms of precision for liver and kidney tumors in clinical setting.
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http://dx.doi.org/10.1080/02656736.2021.1912417DOI Listing
January 2021

A step towards glucose control with a novel nanomagnetic-insulin for diabetes care.

Int J Pharm 2021 May 23;601:120587. Epub 2021 Apr 23.

Division of Biomedical Engineering, University of Saskatchewan, Saskatoon, Canada; School of Mechatronic Engineering and Automation, Shanghai University, Shanghai 200436, PR China. Electronic address:

Massive efforts have been devoted to insulin delivery for diabetes care. Achieving a long-term tight-regulated blood glucose level with a low risk of hypoglycemia remains a great challenge. In this study we propose a novel strategy to efficiently regulate insulin action after insulin is injected or released into patient body aiming to achieve better glycemic control, which is achieved by the administration of insulin-conjugated magnetic nanoparticles (MNPs-Ins). We show that the locomotion of MNPs-Ins can be controlled to reach a target site on an in vitro microfluidic platform, which may open a way to modulate the physiological effect of insulin in a remote-control manner. Most importantly, the in vivo blood glucose regulation of the MNPs-Ins was performed on diabetic mice to understand the glycemic control performance. The results showed that the MNPs-Ins can achieve a better glycemic control with longer effective drug duration while not causing hypoglycemia and a magnetic-modulated hypoglycemic dynamics. Moreover, the in vivo histochemistry experiments confirmed the good biocompatibility of MNPs-Ins. Along with our on-going research on the possibility of the recycle and reuse of the MNPs-Ins, the finding presented in this paper may manifest a fascinating potential in insulin delivery in the near future.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120587DOI Listing
May 2021

Simultaneous Detection of Six Isoforms of Tau Protein in Human Cerebrospinal Fluid by Multidimensional Mass Spectrometry-Based Targeted Proteomics.

J Proteome Res 2021 05 12;20(5):2299-2307. Epub 2021 Apr 12.

School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.

Abnormal expression of Tau protein can cause the development of Alzheimer's disease (AD). So far, much evidence has demonstrated that Tau has multiple isoforms. These isoforms are suggested to have distinct physiological roles and contribute unequally to the progress of AD. Thus, detection of individual Tau isoforms may be helpful to better understand the link between clinical outcome and Tau status and to further improve AD diagnosis and treatment. However, few studies have been conducted on absolute quantification of Tau isoforms, probably due to high sequence homology and also low abundance of these isoforms in biofluids such as cerebrospinal fluid (CSF). Therefore, mass spectrometry-based targeted proteomics was attempted here. This targeted proteomics approach can principally measure a protein of interest at the surrogate peptide level, yet little has been done to detect protein isoforms, probably due to lack of isoform-specific surrogate peptides in mass spectrometry. In this study, separations in more dimensions were added, including immunoprecipitation (IP) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) for sample pretreatment and systems of linear equations for post-lab data extraction. Moreover, the reliability of the approach including IP enrichment, gel separation, and linear algebra algorithms was discussed. As a result, each isoform of Tau protein can be individually detected and quantified. Using IP enrichment, ∼250-fold enhancement of sensitivity was achieved. The ultimate LOQ was 0.50 nM. Finally, this multidimensional mass spectrometry-based targeted proteomics assay was validated and applied to simultaneous quantitative analysis of six Tau isoforms in CSF of AD patients.
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http://dx.doi.org/10.1021/acs.jproteome.0c00826DOI Listing
May 2021

Genomic features underlying the evolutionary transitions of Apibacter to honey bee gut symbionts.

Insect Sci 2021 Apr 3. Epub 2021 Apr 3.

Department of Entomology, College of Plant Protection, China Agricultural University, Beijing, China.

The gut bacteria of honey bee recognized as a mutualistic partner with the insect host might have originated from a free-living or parasitic lifestyle. However, little is known about the genomic features underlying this lifestyle transition. Here we compared the genomes of bee gut bacteria Apibacter with their close relatives living in different lifestyles. We found that despite general reduction in the Apibacter genome, genes involved in amino acid synthesis and monosaccharide detoxification were retained, which is putatively beneficial to the host. Interestingly, the microaerobic Apibacter species specifically acquired genes encoding for the nitrate respiration (NAR). These together with nitrate transporter and enzymatic cofactor synthesis genes were found clustered in the genomes. The NAR system is also conserved in the cohabitating bee gut microbe Snodgrassella, although with a different structure. This convergence suggests a key role of respiratory nitrate reduction for microaerophilic microbiomes to colonize bee gut epithelium. Genes involved in lipid, histidine degradation were found partially or completely lost in Apibacter. Particularly, genes encoding for the conversion to the toxic intermediates in phenylacetate degradation, as well as other potential virulence factors, are specifically lost in Apibacter group. Antibiotic resistance genes are only sporadically distributed among Apibacter species, but are prevalent in their relatives, which may be related to the remotely living feature and less exposure to antibiotics of their bee hosts. Collectively, this study advanced our knowledge of genomic features specialized to bee gut symbionts.
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http://dx.doi.org/10.1111/1744-7917.12912DOI Listing
April 2021

Intradialytic hypotension and cardiac remodeling: should we consider the renin-angiotensin-aldosterone system?

Ren Fail 2021 Dec;43(1):597-598

Department of Nephrology, Second Hospital of Lanzhou University, Lanzhou, PR China.

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http://dx.doi.org/10.1080/0886022X.2021.1901741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018337PMC
December 2021

A review of antenna designs for percutaneous microwave ablation.

Phys Med 2021 Apr 25;84:254-264. Epub 2021 Mar 25.

Energy-based Tumor Ablation Laboratory, School of Mechatronic Engineering and Automation, Shanghai University, Shanghai, China. Electronic address:

Microwave (MW) antenna is a key element in microwave ablation (MWA) treatments as the means that energy is delivered in a focused manner to the tumor and its surrounding area. The energy delivered results in a rise in temperature to a lethal level, resulting in cell death in the ablation zone. The delivery of energy and hence the success of MWA is closely dependent on the structure of the antennas. Therefore, three design criteria, such as expected ablation zone pattern, efficiency of energy delivery, and minimization of the diameter of the antennas have been the focus along the evolution of the MW antenna. To further improve the performance of MWA in the treatment of various tumors through inventing novel antennas, this article reviews the state-of-the-art and summarizes the development of MW antenna designs regarding the three design criteria.
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http://dx.doi.org/10.1016/j.ejmp.2021.03.010DOI Listing
April 2021

Organophosphite Antioxidants in Mulch Films Are Important Sources of Organophosphate Pollutants in Farmlands.

Environ Sci Technol 2021 Jun 23;55(11):7398-7406. Epub 2021 Mar 23.

MOE Key Laboratory of Pollution Processes and Environmental Criteria/Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering, Nankai University, Tianjin 300350, China.

Organophosphite antioxidants (OPAs) are important auxiliary antioxidants used in plastic polymers and can be oxidized to organophosphate esters (OPEs) during production and processing. In this work, the occurrence of OPAs and OPEs in farmlands with or without mulch film applications was investigated. Six OPAs and five OPEs were detected, with the median concentrations of 2.66 ng/g (∑OPAs) and 100 ng/g (∑OPEs) in the film-mulching soil and 1.16 ng/g (∑OPAs) and 47.9 ng/g (∑OPEs) in the nonfilm-mulching soil, respectively. The oxidative derivative of AO168 (tris (2,4-di--butylphenyl) phosphite), a typical OPA, AO168═O (tris (2,4-di--butylphenyl) phosphate) was frequently detected in farmlands at the concentrations of 0-731 ng/g, which is much higher than that of the commercial OPEs (0-12.1 ng/g). This suggests that the oxidation derivatives of OPAs (OPAs═O) might be important OPE contaminants in soils. Mulch films could be their important source. According to the simulation migration experiment, the emission risk ranges of AO168 and AO168═O from mulch films to soils in China were estimated to be 3.96-87.6 and 10.5-95.3 tons/year, respectively, which were much higher than those of OPEs from sewage sludge applications. Simulation experiments also demonstrated that oxidation was the major pathway for OPAs in soils. OPAs with small substituent groups could be potential sources for organophosphate diesters. For the first time, the serious pollution of OPAs and OPAs═O in soils has been reported, and mulch films have been identified as their potential source.
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http://dx.doi.org/10.1021/acs.est.0c08741DOI Listing
June 2021

VEXAS syndrome in myelodysplastic syndrome with autoimmune disorder.

Exp Hematol Oncol 2021 Mar 19;10(1):23. Epub 2021 Mar 19.

State Key Laboratory of Experimental Haematology, Institute of Haematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly-described adult-onset inflammatory syndrome characterized by vacuoles in myeloid and erythroid precursor cells and somatic mutations affecting methionine-41 (p.Met41) in UBA1. The VEXAS syndrome often overlaps with myelodysplastic syndromes (MDS) with autoimmune disorders (AD). By screening the UBA1 gene sequences derived from MDS patients with AD from our center, we identified one patient with a p.Met41Leu missense mutation in UBA1, who should have been diagnosed as MDS comorbid with VEXAS syndrome. This patient respond poorly to immune suppressive drugs. Patients with MDS and AD who have characteristic vacuoles in myeloid and erythroid precursor cells should be screened for UBA1 mutation, these patients are likely to have VEXAS syndrome and unlikely to improve with immunosuppressive drugs and should be considered for other alternative therapies.
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http://dx.doi.org/10.1186/s40164-021-00217-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976711PMC
March 2021

Profiling MicroRNAs with Associated Spatial Dynamics in Acute Tissue Slices.

ACS Nano 2021 03 10;15(3):4881-4892. Epub 2021 Mar 10.

Department of Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong SAR China.

MicroRNAs (miRNAs) are suggested to play important roles in the pathogenesis and progress of human diseases with heterogeneous regulation in different types of cells. However, limited technique is available for profiling miRNAs with both expression and spatial dynamics. Here, we describe a platform for multiplexed miRNA profiling in acute tissue slices. The technique uses diamond nanoneedles functionalized with RNA-binding proteins to directly isolate targeted miRNAs from the cytosol of a large population of cells to achieve a quasi-single-cell analysis for a tissue sample. In addition to a quantitative evaluation of the expression level of particular miRNAs, the technique also provides the relative spatial dynamics of the cellular miRNAs in associated cell populations, which was demonstrated to be useful in analyzing the susceptibility and spatial reorganization of different types of cells in the tissues from normal or diseased animals. As a proof-of-concept, in MK-801-induced schizophrenia model, we found that astrocytes, instead of neurons, are more heterogeneously affected in the hippocampus of rats that underwent repeated injection of MK-801, showing an expression fingerprint related to differentially down-regulated miRNA-135a and miRNA-143; the associated astrocyte subpopulation is also more spatially dispersed in the hippocampus, suggesting an astrocyte dysregulation in the induced schizophrenia animals.
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http://dx.doi.org/10.1021/acsnano.0c09676DOI Listing
March 2021

Advances in CpG Island Methylator Phenotype Colorectal Cancer Therapies.

Front Oncol 2021 26;11:629390. Epub 2021 Feb 26.

Department of Medical Oncology, Dalian University Affiliated Xinhua Hospital, Dalian, China.

With the aging of the population, the incidence of colorectal cancer in China is increasing. One of the epigenetic alterations: CpG island methylator phenotype (CIMP) plays an important role in the incidence of colorectal cancer. Recent studies have shown that CIMP is closely related to some specific clinicopathological phenotypes and multiple molecular phenotypes in colorectal cancer. In this paper, the newest progress of CIMP colorectal cancer in chemotherapeutic drugs, targeted agents and small molecular methylation inhibitors are going to be introduced. We hope to provide potential clinical treatment strategies for personalized and precise treatment of colorectal cancer patients.
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http://dx.doi.org/10.3389/fonc.2021.629390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952756PMC
February 2021

Dielectrophoresis assisted high-throughput detection system for multiplexed immunoassays.

Biosens Bioelectron 2021 May 5;180:113148. Epub 2021 Mar 5.

Department of Clinical Laboratory, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, China. Electronic address:

Digital ELISA is introduced as a novel platform with unique advantages for detecting multiple kinds of single-molecule in the sample. How to improve the sensitivity of detection is the direction of current related research. Here, we report an immunoassay method that applied electrokinetic effects to isolate the individual encoded beads and confine in micro-wells to improve the efficiency of cytokines detection simultaneously. The microfluidic design provided a non-uniform electric field to induce dielectrophoresis (DEP) force and to manipulate the beads. Two wavelengths of excitation light excited the encoded beads for simultaneous detection of reporters. The light was confined to the bottom slide via the principle of total internal reflection. Finally, the concentration of captured cytokines was obtained by picking up each bead from the image and then integrating the intensity of fluorescent light emitted from the reporters. The results demonstrated that the fill percentage of encoded beads was raised from 10-20% to 60-80% via DEP effect. By comparing the fluorescence color of the particle, itself and its surface, the concentration of four target cytokines, IL-2, IL-6, IL-10 and TNF-α, were calculated to the pg/ml level. The spike and recovery experiments verified the efficiency, more than 70% of the target molecules were captured. The reliability of our method was verified by flow cytometry as well. In conclusion, we expect the application of DEP can increase the sensitivity of digital ELISA for multiple rapid detection.
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http://dx.doi.org/10.1016/j.bios.2021.113148DOI Listing
May 2021

Nanocapillarity and Nanoconfinement Effects of Pipet-like [email protected] Nanotubes for Highly Efficient Electrocatalytic CO Reduction.

Nano Lett 2021 Mar 12;21(6):2650-2657. Epub 2021 Mar 12.

MOE Key Laboratory of Mesoscopic Chemistry, MOE Key Laboratory of High Performance Polymer Materials and Technology, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.

Electrocatalytic CO reduction reaction is regarded as an intriguing route for producing renewable chemicals and fuels, but its development is limited by the lack of highly efficient and stable electrocatalysts. Herein, we propose the pipet-like bismuth (Bi) nanorods semifilled in nitrogen-doped carbon nanotubes ([email protected]) for highly selective electrocatalytic CO reduction. Benefited from the prominent capillary and confinement effects, the [email protected] act as nanoscale conveyors that can significantly facilitate the mass transport, adsorption,and concentration of reactants onto the active sites, realizing rapid reaction kinetics and low cathodic polarization. The spatial encapsulation and separation by the NCNT shells prevents the self-aggregation and surface oxidation of Bi-NRs, increasing the dispersity and stability of the electrocatalyst. As a result, the [email protected] exhibit high activity and durable catalytic stability for CO-to-formate conversion over a wide potential range. The Faradaic efficiency for formate production reaches 90.9% at a moderate applied potential of -0.9 V vs reversible hydrogen electrode (RHE).
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http://dx.doi.org/10.1021/acs.nanolett.1c00390DOI Listing
March 2021

Dassonmycins A and B, Polycyclic Thioalkaloids from a Marine Sponge-Derived SCSIO 40065.

Org Lett 2021 04 11;23(8):2858-2862. Epub 2021 Mar 11.

Key Laboratory of Tropical Marine Bioresources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.

Two polycyclic thioalkaloides dassonmycins A () and B () were isolated from SCSIO 40065 associated with marine sponge sp. Structures of and were elucidated by comprehensive spectroscopic analysis and confirmed by single-crystal X-ray diffraction experiments, to have a 6/6/6/6-fused tetracyclic ring featuring a naphthoquinone[2,3-]piperazine[1,2-]thiomorpholine scaffold. Compound formed a caged core through an additional ether bridge. Both compounds exhibited moderate antibacterial and cytotoxic activities.
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http://dx.doi.org/10.1021/acs.orglett.1c00328DOI Listing
April 2021

Cylindromicin from Arctic-Derived Fungus sp. SCSIO 40433.

Molecules 2021 Feb 18;26(4). Epub 2021 Feb 18.

Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China.

The fungus strain SCSIO 40433 was isolated from an Arctic-derived glacier sediment sample and characterized as . A new compound, cylindromicin (), and seven known secondary metabolites (-) were isolated from this strain. The chemical structures of these compounds were elucidated by comprehensive spectroscopic analyses. Cylindromicin () featured a 3,4-dihydro-2-pyran skeleton. The absolute configuration of compound was assigned via interpretation of key Nuclear Overhauser Effect Spectroscopy (NOESY) correlations and Electronic Circular Dichroism (ECD) calculation. Cylindromicin () exhibited significant tyrosinase inhibition activity. This study highlights Polar fungi as a potential resource for new bioactive natural products.
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http://dx.doi.org/10.3390/molecules26041080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922244PMC
February 2021

Comparison of porcine corneal decellularization methods and importance of preserving corneal limbus through decellularization.

PLoS One 2021 5;16(3):e0243682. Epub 2021 Mar 5.

Transplant Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, Indianapolis, United States of America.

Background: The aim of this study is to compare the three previously applied, conventional porcine corneal decellularization methods and to demonstrate the importance of preserving the corneal limbus through decellularization.

Methods: Fresh, wild-type (with or without) limbus porcine corneas were decellularized using three different methods, including (i) sodium dodecyl sulfate (SDS), (ii) hypertonic saline (HS), and (iii) N2 gas (NG). Post-treatment evaluation was carried out using histological, residual nuclear material, and ultrastructural analyses. Glycerol was used to help reduce the adverse effects of decellularization. The corneas were preserved for two weeks in cornea storage medium.

Results: All three decellularization methods reduced the number of keratocytes at different rates in the stromal tissue. However, all methods, except SDS, resulted in the retention of large numbers of cells and cell fragments. The SDS method (0.1% SDS, 48h) resulted in almost 100% decellularization in corneas without limbus. Low decellularization capacity of the NG method (<50%) could make it unfavorable. Although HS method had a more balanced damage-decellularization ratio, its decellularization capacity was lower than SDS method. Preservation of the corneoscleral limbus could partially prevent structural damage and edema, but it would reduce the decellularization capacity.

Conclusion: Our results suggest that SDS is a very powerful decellularization method, but it damages the cornea irreversibly. Preserving the corneoscleral limbus reduces the efficiency of decellularization, but also reduces the damage.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243682PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935270PMC
March 2021

Mutanofactin promotes adhesion and biofilm formation of cariogenic Streptococcus mutans.

Nat Chem Biol 2021 05 4;17(5):576-584. Epub 2021 Mar 4.

Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA, USA.

Cariogenic Streptococcus mutans is known as a predominant etiological agent of dental caries due to its exceptional capacity to form biofilms. From strains of S. mutans isolated from dental plaque, we discovered, in the present study, a polyketide/nonribosomal peptide biosynthetic gene cluster, muf, which directly correlates with a strong biofilm-forming capability. We then identified the muf-associated bioactive product, mutanofactin-697, which contains a new molecular scaffold, along with its biosynthetic logic. Further mode-of-action studies revealed that mutanofactin-697 binds to S. mutans cells and also extracellular DNA, increases bacterial hydrophobicity, and promotes bacterial adhesion and subsequent biofilm formation. Our findings provided an example of a microbial secondary metabolite promoting biofilm formation via a physicochemical approach, highlighting the importance of secondary metabolism in mediating critical processes related to the development of dental caries.
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http://dx.doi.org/10.1038/s41589-021-00745-2DOI Listing
May 2021

miR-744-5p Inhibits Multiple Myeloma Proliferation, Epithelial Mesenchymal Transformation and Glycolysis by Targeting SOX12/Wnt/β-Catenin Signaling.

Onco Targets Ther 2021 22;14:1161-1172. Epub 2021 Feb 22.

Department of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, People's Republic of China.

Purpose: This study investigated the function and molecular mechanisms of miR-744-5p in multiple myeloma (MM).

Methods: miR-744-5p and SRY-related high-mobility-group box 12 (SOX12) expression in clinical tissues and MM cells was monitored by quantitative real-time polymerase chain reactions and Western blot. miR-744-5p expression in MM cells was regulated by transfection. Cell proliferation was researched by cell counting kit-8 assay and plate clone formation experiment. Transwell experiment was utilized for migration and invasion detection. Glycolysis test was conducted for the detection of glucose uptake and lactate production of MM cells. The relationship between miR-744-5p and SOX12 was determined by dual-luciferase reporter gene assay and RNA pull-down experiment. In vivo experiment was conducted using nude mice.

Results: miR-744-5p expression was reduced in MM patients (<0.01). Low miR-744-5p expression was associated with lower 60-month survival in MM patients (=0.0402). miR-744-5p overexpression inhibited MM cells proliferation, invasion, migration, glucose uptake, lactate production, and epithelial mesenchymal transformation (EMT) (<0.01). miR-744-5p directly inhibited SOX12 expression. miR-744-5p silencing promoted MM cells proliferation, invasion, migration, glucose uptake, lactate production, and EMT by elevating SOX12 (<0.01). miR-744-5p inhibited the growth of MM xenograft tumors in vivo (<0.001).

Conclusion: miR-744-5p inhibits MM cells proliferation, invasion, migration, EMT, and glycolysis by targeting SOX12/Wnt/β-catenin.
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http://dx.doi.org/10.2147/OTT.S270636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910092PMC
February 2021

The efficacy and safety of glucokinase activators for the treatment of type-2 diabetes mellitus: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Feb;100(7):e24873

Affiliated Hospital of Shaoxing University of Edocrine and Metabolism Department, Zhejiang, China.

Background: Glucokinase activators are a novel family of glucose-lowering agents used for the treatment of type-2 diabetes mellitus (T2DM). Glucokinase activators blind to GK activate the enzyme allosterically. Treatment with different GKAs has been shown to reduce fasting and postprandial glucose in patients with type 2 diabetes. We compared the efficacy/safety of glucokinase activators in T2DM patients through a meta-analysis.

Methods: We searched PubMed, Excerpt Medica Database, and Cochrane Central Register of Controlled Trials databases for articles published before December 30, 2020. Two independent reviewers extracted the information from article. The quality of articles were assessed by 2 independent reviewers using the 5 items of scale proposed by Jadad. We computed the weighted mean difference and 95% confidence interval (CI) for a change from baseline to the study endpoint for glucokinase activators vs placebo. Egger test and Begg test were used to assess the possible publication bias caused by the tendency of published studies to be positive.

Results: The present meta-analysis will compare the efficacy and safety of glucokinase activators and placebo for the treatment of T2DM.

Conclusions: This meta-analysis will provide advanced evidence on the efficacy and safety of glucokinase activators for the treatment of T2DM.

Ethics And Dissemination: Ethical approval and patient consent are not required because this study is a literature-based study. This systematic review and meta-analysis will be published in a peer-reviewed journal.

Prospero Registration Number: CRD42021220364.
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http://dx.doi.org/10.1097/MD.0000000000024873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899907PMC
February 2021