Publications by authors named "Dapeng Zhang"

269 Publications

Targeted Delivery of mRNA with One-Component Ionizable Amphiphilic Janus Dendrimers.

J Am Chem Soc 2021 Oct 21. Epub 2021 Oct 21.

Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6323, United States.

Targeted and efficient delivery of nucleic acids with viral and synthetic vectors is the key step of genetic nanomedicine. The four-component lipid nanoparticle synthetic delivery systems consisting of ionizable lipids, phospholipids, cholesterol, and a PEG-conjugated lipid, assembled by microfluidic or T-tube technology, have been extraordinarily successful for delivery of mRNA to provide Covid-19 vaccines. Recently, we reported a one-component multifunctional sequence-defined ionizable amphiphilic Janus dendrimer (IAJD) synthetic delivery system for mRNA relying on amphiphilic Janus dendrimers and glycodendrimers developed in our laboratory. Amphiphilic Janus dendrimers consist of functional hydrophilic dendrons conjugated to hydrophobic dendrons. Co-assembly of IAJDs with mRNA into dendrimersome nanoparticles (DNPs) occurs by simple injection in acetate buffer, rather than by microfluidic devices, and provides a very efficient system for delivery of mRNA to lung. Here we report the replacement of most of the hydrophilic fragment of the dendron from IAJDs, maintaining only its ionizable amine, while changing its interconnecting group to the hydrophobic dendron from amide to ester. The resulting IAJDs demonstrated that protonated ionizable amines play dual roles of hydrophilic fragment and binding ligand for mRNA, changing delivery from lung to spleen and/or liver. Replacing the interconnecting ester with the amide switched the delivery back to lung. Delivery predominantly to liver is favored by pairs of odd and even alkyl groups in the hydrophobic dendron. This simple structural change transformed the targeted delivery of mRNA mediated with IAJDs, from lung to liver and spleen, and expands the utility of DNPs from therapeutics to vaccines.
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http://dx.doi.org/10.1021/jacs.1c09585DOI Listing
October 2021

Down-regulated expression of miR-582 predicts poor prognosis and facilitates melanoma progression by targeting FOXC1.

Arch Dermatol Res 2021 Oct 10. Epub 2021 Oct 10.

Department of Burn Plastic Surgery, Binzhou Medical University Hospital, No. 661 Huanghe 2nd Road, Binzhou, 256603, Shandong, China.

Melanoma is one of the most common malignant tumors that originate from nerve sheath melanocytes and are produced in the skin and other organs. This paper mainly studied the role of miR-582 in melanoma. The expression of miR-582 in melanoma cell lines and tissues was evaluated by real-time quantitative PCR. Kaplan-Meier curve and Cox proportional hazards model analysis were used to investigate the prognostic value of miR-582 in melanoma. Cell proliferation, invasion, and migration were analyzed using CCK-8 and transwell assays. The results showed that miR-582 was significantly decreased in melanoma cells and tissues. Downregulation of miR-582 was associated with ulceration, lymph node metastasis, TNM stage, and poor overall survival. The functional results showed that low expression of miR-582 can promote cell proliferation, migration, and invasion. FOXC1 was a direct target of miR-582. Overall, the expression of miR-582 is downregulated in melanoma tissues and cell lines. Low expression of miR-582 is associated with prognosis and progression of melanoma by targeting FOXC1. miR-582 may be a prognostic biomarker and a new therapeutic strategy for melanoma.
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http://dx.doi.org/10.1007/s00403-021-02285-0DOI Listing
October 2021

Comparative Phylogenomic Analysis Reveals Evolutionary Genomic Changes and Novel Toxin Families in Endophytic Pathogens.

Microbiol Spectr 2021 Sep 15:e0050921. Epub 2021 Sep 15.

Department of Biology, College of Arts & Sciences, Saint Louis Universitygrid.262962.b, St. Louis, Missouri, USA.

pathogens are the causative agents of several severe crop diseases worldwide, including citrus Huanglongbing and potato zebra chip. These bacteria are endophytic and nonculturable, which makes experimental approaches challenging and highlights the need for bioinformatic analysis in advancing our understanding about pathogenesis. Here, we performed an in-depth comparative phylogenomic analysis of the pathogens and their free-living, nonpathogenic, ancestral species, aiming to identify major genomic changes and determinants associated with their evolutionary transitions in living habitats and pathogenicity. Using gene neighborhood analysis and phylogenetic classification, we systematically uncovered, annotated, and classified all prophage loci into four types, including one previously unrecognized group. We showed that these prophages originated through independent gene transfers at different evolutionary stages of and only the SC-type prophage was associated with the emergence of the pathogens. Using ortholog clustering, we vigorously identified two additional sets of genomic genes, which were either lost or gained in the ancestor of the pathogens. Consistent with the habitat change, the lost genes were enriched for biosynthesis of cellular building blocks. Importantly, among the gained genes, we uncovered several previously unrecognized toxins, including new toxins homologous to the EspG/VirA effectors, a YdjM phospholipase toxin, and a secreted endonuclease/exonuclease/phosphatase (EEP) protein. Our results substantially extend the knowledge of the evolutionary events and potential determinants leading to the emergence of endophytic, pathogenic species, which will facilitate the design of functional experiments and the development of new methods for detection and blockage of these pathogens. pathogens are associated with several severe crop diseases, including citrus Huanglongbing, the most destructive disease to the citrus industry. Currently, no effective cure or treatments are available, and no resistant citrus variety has been found. The fact that these obligate endophytic pathogens are not culturable has made it extremely challenging to experimentally uncover the genes/proteins important to pathogenesis. Further, earlier bioinformatics studies failed to identify key genomic determinants, such as toxins and effector proteins, that underlie the pathogenicity of the bacteria. In this study, an in-depth comparative genomic analysis of pathogens along with their ancestral nonpathogenic species identified the prophage loci and several novel toxins that are evolutionarily associated with the emergence of the pathogens. These results shed new light on the disease mechanism of pathogens and will facilitate the development of new detection and blockage methods targeting the toxins.
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http://dx.doi.org/10.1128/Spectrum.00509-21DOI Listing
September 2021

N-Glycosylation and enzymatic activity of the rHuPH20 expressed in Chinese hamster ovary cells.

Anal Biochem 2021 Nov 11;632:114380. Epub 2021 Sep 11.

State Key Laboratory of Antibody Medicine and Targeted Therapy, Shanghai, 201203, China; NMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies, Shanghai, 201203, China; School of Pharmacy, Liaocheng University, Liaocheng, 252000, China. Electronic address:

rHuPH20, a neutral pH-active hyaluronidase that degrades glycosaminoglycans under physiologic conditions, has six potential N-glycosylation sites. In this report, the rHuPH20 expressed in Chinese hamster ovary (CHO) cells was analyzed and characterized using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Removal of the N-linked glycans from rHuPH20 with PNGase F shifted the molecular weight from 66 kDa to approximately 52 kDa, its deduced molecular weight based on sequence analysis, suggesting that most, if not all, of the potential N-glycosylation sites are linked to oligosaccharides. Then the N-linked glycans released from the rHuPH20 by PNGase F were characterized by UPLC-FLR-MS, and the six N-glycosylation sites of the rHuPH20 were identified and characterized by UPLC-MS/MS at peptide levels. Subsequently, we found that the rHuPH20 increased the dispersion of locally subcutaneous injected drugs and the in vitro and in vivo bioactivity were decreased significantly after PNGase F treatment. In particular, rHuPH20 significantly augmented the absolute bioavailability of locally subcutaneous injected large protein therapeutics, while the bioavailability decreased after being digested by PNGase F. These results demonstrated that N-glycosylation is important for the bioactivity of the rHuPH20.
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http://dx.doi.org/10.1016/j.ab.2021.114380DOI Listing
November 2021

How size, edge shape, functional groups and embeddedness influence the electronic structure and partial optical properties of graphene nanoribbons.

Phys Chem Chem Phys 2021 Sep 22;23(36):20695-20701. Epub 2021 Sep 22.

School of Chemistry and Chemical Engineering, Qufu Normal University, P. R. China.

The armchair and zigzag edge shape makes graphene nanoribbons (GNRs) exhibit interest in different applications. However, the relationship between influencing factors and properties is not clear. Herein, the many-body Green's function theory and the TDDFT method are used to investigate the effect of size, edge shape and functional groups on the electronic and optical properties of GNRs and h-BN-embedded GNRs. We find that ZGNRs have a smaller band gap and absorption edge than AGNRs having the same size and functional groups. The relationship between S and T is mainly determined by the size and edge shape of GNRs, while the redox ability of water splitting mainly relies on the kind of the functional group. When h-BN is embedded in GNRs, the edge shape of GNRs and the contact part between two substances control the direction of electron transfer in both the ground state and the excited state. These results can provide theoretical support for further improvements and applications of GNRs.
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http://dx.doi.org/10.1039/d1cp02689eDOI Listing
September 2021

Titanium Cage in Comparison with Nano-Hydroxyapatite Bone Graft Substitutes in Cervical Reconstruction.

J Biomed Nanotechnol 2021 Jul;17(7):1448-1452

Department of Orthopedics, Fourth Affiliated Hospital of Harbin Medical University, Nangang District, Harbin 150001, Heilongjiang Province, China.

Cervical spondylosis is a disease that occurs with age and affects the discs and joints in the cervical spine located in the neck. The hydroxyapatite (HA) bone graft substitutes can used as a potential bone-forming agent, however, the efficacy of using HA is challenging in cervical reconstruction. In this regard, nano-based HA was used in this study to explore its sagittal parameters and clinical potency in relative to titanium (TiO₂) cage in patient with cervical spondylosis. 50 patients suffering from cervical spondylosis were divided in two groups and were grafted with either TiO₂ cage or nano-HA. The sagittal parameters, including cervical spine lateral radiographs (CCoob and CCoob) were taken pre- and post-operation (3-month, one-year and two-year). The clinical potency was also done based on the JOA scores. Angle analysis indicated that the CCobb and CCobb angles were significantly changed after the operation in both TiO₂ cage and nano-HA groups, whereas no significant changes was determined in nano-HA relative to TiO₂ cage condition. Also, it was shown that JOA scores were significantly higher after the operation than pre-operation, indicating a potential cervical reconstruction after surgery in both groups which slightly were higher for nano-HA groups.
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http://dx.doi.org/10.1166/jbn.2021.3121DOI Listing
July 2021

Sequencing and de Novo Assembly of Abaca ( Née) var. Abuab Genome.

Genes (Basel) 2021 Aug 2;12(8). Epub 2021 Aug 2.

Sustainable Perennial Crops Laboratory, USDA-ARS, Beltsville, MD 20705, USA.

Abaca ( Née), an indigenous crop to the Philippines, is known to be the source of the strongest natural fiber. Despite its huge economic contributions, research on crop improvement is limited due to the lack of genomic data. In this study, the whole genome of the abaca var. Abuab was sequenced using Illumina Novaseq 6000 and Pacific Biosciences Single-Molecule Real-Time Sequel. The genome size of Abuab was estimated to be 616 Mbp based on total k-mer number and volume peak. Its genome was assembled at 65× depth, mapping 95.28% of the estimated genome size. BUSCO analysis recovered 78.2% complete BUSCO genes. A total of 33,277 gene structures were predicted which is comparable to the number of predicted genes from recently assembled Musa spp. genomes. A total of 330 Mbp repetitive elements were also mined, accounting to 53.6% of the genome length. Here we report the sequencing and genome assembly of the abaca var. Abuab that will facilitate gene discovery for crop improvement and an indispensable source for genetic diversity studies in Musa.
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http://dx.doi.org/10.3390/genes12081202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392402PMC
August 2021

The effects of MIR137HG genetic polymorphisms on the susceptibility of alcohol-induced osteonecrosis of the femoral head in a Chinese male population.

Gene 2021 Dec 14;804:145902. Epub 2021 Aug 14.

Department of Orthopedics, Zhengzhou Traditional Chinese Hospital of Orthopaedics, Zhengzhou, Henan 450000, China.

Backgrounds: Osteonecrosis of the femoral head (ONFH) is one of the common and complicated diseases in the orthopedic clinic. Previous studies indicate that genetic factors play a crucial role in the occurrence of ONFH. This case-control study aimed to investigate the associations of MIR137HG genetic polymorphisms with the alcohol-induced ONFH risk.

Methods: A total of 731 participants were recruited to detect the effect of MIR137HG SNPs on the alcohol-induced ONFH risk in a Chinese male population. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the associations. Multifactor dimensionality reduction (MDR) was used to analyze the SNP-SNP interaction with the alcohol-induced ONFH risk.

Results: Our study showed that rs7549905 played a protective role in alcohol-induced ONFH risk (OR 0.57, p = 0.045). Stratified analysis indicated that rs9440302 was associated with an increased risk of patients aged >45 years (OR 2.00, p = 0.038), and rs7549905 showed a reduced risk in patients aged ≤ 45 years (OR 0.43, p = 0.023). In addition, we found that rs9440302 and rs7554283 exhibited a significantly increased susceptibility of III-IV grade alcohol-induced ONFH patients (OR 2.34, p = 0.003; OR 2.13, p = 0.011, respectively). We also observed that rs12138817 was related to an increased risk in patients with >21 months of course (OR 1.77, p = 0.043). Interestingly, rs17371457 showed a significant correlation with low-density lipoprotein-cholesterol (p = 0.040).

Conclusion: Our study suggests that MIR137HG genetic variants are associated with the alcohol-induced ONFH susceptibility in a Chinese male population, which may give scientific evidence for exploring molecular mechanisms of the alcohol-induced ONFH.
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http://dx.doi.org/10.1016/j.gene.2021.145902DOI Listing
December 2021

Environmental Risk Assessment of Recycled Products of Spent Coppery Etchant in Jiangsu Province, China.

Int J Environ Res Public Health 2021 07 26;18(15). Epub 2021 Jul 26.

Nanjing Institute of Environmental Science, Ministry of Ecology and Environment of China, Nanjing 210042, China.

With the vigorous development of the 5G industry, the characteristic hazardous waste, spent coppery etchant, was also produced in large quantities. In recent years, there are many companies that have begun to collect spent coppery etchant for the purpose of producing recycled products, such as copper sulfate, copper oxide, basic copper chloride, and copper powder, which often contain large amounts of heavy metals. However, due to the lack of relevant standards and applicable regulatory measures, some of the recycled products flow to the feed processing industry and even to the food processing industry. This study investigated the pollution status of heavy metals in recycled products of spent coppery etchant and evaluated the impact of recycled products exposure on human health. The results showed that the content of Zn was the highest, which was 21 times higher than the corresponding standard limit. Human health risk assessment indicated that the hazard quotients of As account for 87.5% of the entire HI value, while the average carcinogenic risk values of As for copper sulfate, copper oxide, basic copper chloride, and copper powder are 1.09 × 10, 3.19 × 10, 1.29 × 10, 7.94 × 10, respectively. Meanwhile, suggestions on the supervision of recycled products and the concentration limits of heavy metals in recycled products were put forward.
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http://dx.doi.org/10.3390/ijerph18157881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345568PMC
July 2021

Reactivation of tumour suppressor in breast cancer by enhancer switching through NamiRNA network.

Nucleic Acids Res 2021 Sep;49(15):8556-8572

Shanghai Public Health Clinical Center and Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute and Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, P. R. China.

Dysfunction of Tumour Suppressor Genes (TSGs) is a common feature in carcinogenesis. Epigenetic abnormalities including DNA hypermethylation or aberrant histone modifications in promoter regions have been described for interpreting TSG inactivation. However, in many instances, how TSGs are silenced in tumours are largely unknown. Given that miRNA with low expression in tumours is another recognized signature, we hypothesize that low expression of miRNA may reduce the activity of TSG related enhancers and further lead to inactivation of TSG during cancer development. Here, we reported that low expression of miRNA in cancer as a recognized signature leads to loss of function of TSGs in breast cancer. In 157 paired breast cancer and adjacent normal samples, tumour suppressor gene GPER1 and miR-339 are both downregulated in Luminal A/B and Triple Negative Breast Cancer subtypes. Mechanistic investigations revealed that miR-339 upregulates GPER1 expression in breast cancer cells by switching on the GPER1 enhancer, which can be blocked by enhancer deletion through the CRISPR/Cas9 system. Collectively, our findings reveal novel mechanistic insights into TSG dysfunction in cancer development, and provide evidence that reactivation of TSG by enhancer switching may be a promising alternative strategy for clinical breast cancer treatment.
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http://dx.doi.org/10.1093/nar/gkab626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421228PMC
September 2021

One-Component Multifunctional Sequence-Defined Ionizable Amphiphilic Janus Dendrimer Delivery Systems for mRNA.

J Am Chem Soc 2021 08 29;143(31):12315-12327. Epub 2021 Jul 29.

Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6323, United States.

Efficient viral or nonviral delivery of nucleic acids is the key step of genetic nanomedicine. Both viral and synthetic vectors have been successfully employed for genetic delivery with recent examples being DNA, adenoviral, and mRNA-based Covid-19 vaccines. Viral vectors can be target specific and very efficient but can also mediate severe immune response, cell toxicity, and mutations. Four-component lipid nanoparticles (LNPs) containing ionizable lipids, phospholipids, cholesterol for mechanical properties, and PEG-conjugated lipid for stability represent the current leading nonviral vectors for mRNA. However, the segregation of the neutral ionizable lipid as droplets in the core of the LNP, the "PEG dilemma", and the stability at only very low temperatures limit their efficiency. Here, we report the development of a one-component multifunctional ionizable amphiphilic Janus dendrimer (IAJD) delivery system for mRNA that exhibits high activity at a low concentration of ionizable amines organized in a sequence-defined arrangement. Six libraries containing 54 sequence-defined IAJDs were synthesized by an accelerated modular-orthogonal methodology and coassembled with mRNA into dendrimersome nanoparticles (DNPs) by a simple injection method rather than by the complex microfluidic technology often used for LNPs. Forty four (81%) showed activity and 31 (57%) . Some, exhibiting organ specificity, are stable at 5 °C and demonstrated higher transfection efficiency than positive control experiments and . Aside from practical applications, this proof of concept will help elucidate the mechanisms of packaging and release of mRNA from DNPs as a function of ionizable amine concentration, their sequence, and constitutional isomerism of IAJDs.
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http://dx.doi.org/10.1021/jacs.1c05813DOI Listing
August 2021

Caveolin-1 increases glycolysis in pancreatic cancer cells and triggers cachectic states.

FASEB J 2021 08;35(8):e21826

The Laboratory of Acute Abdomen Disease Associated Organ Injury and Repair, Nankai Hospital Affiliated to Nankai University, Tianjin, China.

In pancreatic cancer, autocrine insulin-like growth factor-1 (IGF-1) and paracrine insulin stimulate both IGF-1 receptor (IGF1R) and insulin receptor (IR) to increase tumor growth and glycolysis. In pancreatic cancer patients, cancer-induced glycolysis increases hepatic gluconeogenesis, skeletal muscle proteolysis, and fat lipolysis and, thereby, causes cancer cachexia. As a protein coexisting with IGF1R and IR, caveolin-1 (cav-1) may be involved in pancreatic cancer-induced cachexia. We undertook the present study to test this hypothesis. Out of wild-type MiaPaCa2 and AsPC1 human pancreatic cancer cell lines, we created their stable sub-lines whose cav-1 expression was diminished with RNA interference or increased with transgene expression. When these cells were studied in vitro, we found that cav-1 regulated IGF1R/IR expression and activation and also regulated cellular glycolysis. We transplanted the different types of MiaPaCa2 cells in growing athymic mice for 8 weeks, using intact athymic mice as tumor-free controls. We found that cav-1 levels in tumor grafts were correlated with expression levels of the enzymes that regulated hepatic gluconeogenesis, skeletal muscle proteolysis, and fat lipolysis in the respective tissues. When the tumors had original or increased cav-1, their carriers' body weight gain was less than the tumor-free reference. When cav-1 was diminished in tumors, the tumor carriers' body weight gain was not changed significantly, compared to the tumor-free reference. In conclusion, cav-1 in pancreatic cancer cells stimulated IGF1R/IR and glycolysis in the cancer cells and triggered cachectic states in the tumor carrier.
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http://dx.doi.org/10.1096/fj.202100121RRRDOI Listing
August 2021

Acidic pH irreversibly activates the signaling enzyme SARM1.

FEBS J 2021 Jul 2. Epub 2021 Jul 2.

Department of Biology, College of Arts and Sciences, Saint Louis University, MO, USA.

SARM1, an executioner in axon degeneration, is an autoinhibitory NAD-consuming enzyme, composed of multiple domains. NMN and its analogs, CZ-48 and VMN, are the only known activators, which can release the inhibitory ARM domain from the enzymatic TIR domain. Here, we document that acid can also activate SARM1, even more efficiently than NMN, possibly via the protonation of the negative residues. Systematic mutagenesis revealed that a single mutation, E689Q in TIR, led to the constitutive activation of SARM1. It forms a salt bridge with R216 in the neighboring ARM, maintaining the autoinhibitory structure. Using this 'acid activation' protocol, mutation K597E was found to inhibit activation, while H685A eliminated SARM1 catalytic activity, revealing two distinct inhibitory mechanisms. The protocol has also been applied to differentiate two classes of chemical inhibitors. NAD, dHNN, disulfiram, CHAPS, and TRX-100 mainly inhibited the activation process, while nicotinamide and Tweens mainly inhibited SARM1 catalysis. Taken together, we demonstrate a new mechanism for SARM1 activation and decipher two distinct inhibitory mechanisms of SARM1.
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http://dx.doi.org/10.1111/febs.16104DOI Listing
July 2021

[Application of affinity capillary electrophoresis in the study of protein-DNA interactions].

Se Pu 2020 Oct;38(10):1133-1142

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

Protein-DNA interactions play essential roles in various biological events that determine the cell fate. Research on the molecular mechanism of protein-DNA interactions has helped elucidate diverse fundamental life processes, thereby providing theoretical guidance for establishing clinical treatment and screening potential drug of target diseases. Furthermore, well-known protein-DNA interactions have been utilized to develop advanced bioengineering and bioanalytical techniques, therefore providing robust technical support for related research. Hence, it is important to establish sensitive and rapid analytical methods to study protein-DNA interactions. High-performance capillary electrophoresis (CE) has been widely used in many research fields such as chemistry, life sciences, and environmental sciences, mainly due to its advantages including ultra-high separation efficiency, extremely low sample consumption, and short analysis time. For instance, affinity capillary electrophoresis (ACE) has become an important analytical tool for investigating molecular interactions. In this paper, we review the applications of ACE in studying protein-DNA interactions since it was first proposed in 1992, addressing previous significant work in this field. Three major aspects have been summarized in this review: (1) brief introduction to the development of ACE technique; (2) applications of ACE in the fundamental research on the molecular mechanism of protein-DNA interactions; and (3) applications of well-known protein-DNA interactions in CE-based detection of target molecules and reactions. In the first aspect, along with the concept and separation modes of ACE, general strategies to enhance the analytical ability of ACE are briefly introduced. In the second aspect, the applications of ACE in studying several important protein-DNA interactions involving transcription factors (e.g., GCN4), DNA repair proteins (e.g., UvrA, UvrB, and RecA), and methylated DNA-binding proteins (MBDs) are reviewed. In the third aspect, the applications of well-known molecular interactions (e.g., antigen-antibody, aptamer-target, etc.) to facilitate CE-based detection of target molecules (e.g., DNA adducts, DNA methylation, microRNA, single nucleotide polymorphism, etc.) and target reactions (e.g., DNA strand exchange) are addressed. Finally, we prospect and discuss the advancements of ACE that can be established in future studies. The following two aspects should be improved in future ACE analysis: (1) the advantages of extremely low volume consumption and short analysis time should be fully utilized to develop sensitive and high-throughput CE platforms for the assessment of rare biological samples and massive uncertain samples, respectively; (2) ACE should be combined with other advanced techniques, such as DNA sequencing and mass spectrometry, to rapidly screen and identify the precise interacting sites of unknown protein-DNA interactions.
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http://dx.doi.org/10.3724/SP.J.1123.2020.03007DOI Listing
October 2020

Precise sequencing of single protected-DNA fragment molecules for profiling of protein distribution and assembly on DNA.

Chem Sci 2021 Jan 2;12(6):2039-2049. Epub 2021 Jan 2.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences Beijing 100085 P. R. China +86 10 62849600 +86 10 62849600.

Multiple DNA-interacting protein molecules are often dynamically distributed and/or assembled along a DNA molecule to adapt to their intricate functions temporally. However, analytical technology for measuring such binding behaviours is still missing. Here, we demonstrate the unique capacity of a supernuclease for a highly efficient cutting of the unprotected-DNA segments and with complete preservation of the protein-occluded DNA segments at near single-nucleotide resolution. By exploring this high-resolution cutting, an unprecedented assay that allows a precise sequencing of single protected-DNA fragment molecules (SPDFMS) was developed. As relevant applications, relevant information was gained on the respective distribution/assembly patterns and coordinated displacement of single-stranded DNA-binding protein and recombinase RecA, two model proteins, on DNA. Benefiting from this assay, we also for the first time provide direct measurement of the length of single RecA nucleofilaments, showing the predominant stoichiometry of 5-7 RecA monomers per RecA nucleofilament under physiologically relevant conditions. This innovative assay appears as a promising analytical tool for studying diverse protein-DNA interactions implicated in DNA replication, transcription, recombination, repair, and gene editing.
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http://dx.doi.org/10.1039/d0sc01742fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179319PMC
January 2021

Design of an efficient photocatalyst: a type II heterojunction for enhanced hydrogen production driven by visible light.

Phys Chem Chem Phys 2021 May;23(20):11893-11899

School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, P. R. China.

Solar hydrogen production, which is an eco-friendly method to obtain energy, is still far away from wide commercialization due to the lack of an efficient catalyst. Effective calculations can reduce trial and error costs and provide mechanistic explanations while exploring efficient catalysts. Herein, a type II heterojunction Mg-containing-porphyrin/g-C3N4 is proven to be an efficient photocatalyst by using a combination of DFT and many-body Green's function theory. Our results show that the heterojunction can significantly enhance the absorption of visible light and realize the separation of photogenerated electrons and holes after excitation. Subsequently, water absorbing on the excited surface decomposes into H+ and OH- easily, and then produces H2 and O2 with reduced free energy. Our investigation and explanation can provide theoretical support for designing photonic devices based on porphyrin and g-C3N4, and deepen the understanding of how H2O splits into H2.
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http://dx.doi.org/10.1039/d1cp00347jDOI Listing
May 2021

Genomic and in vitro pharmacodynamic analysis of rifampicin resistance in multidrug-resistant canine Staphylococcus pseudintermedius isolates.

Vet Dermatol 2021 Jun 21;32(3):219-e67. Epub 2021 Apr 21.

Department of Clinical Sciences, Auburn University, Auburn, AL, 36849, USA.

Background: Antimicrobial resistance is a growing concern in canine Staphylococcus pseudintermedius dermatitis. Treatment with rifampicin (RFP) is considered only in meticillin-resistant and multidrug-resistant S. pseudintermedius (MDR-MRSP).

Hypothesis/objectives: To determine an optimal RFP dosing for MDR-MRSP treatment without induction of RFP resistance and identify causal mutations for antimicrobial resistance.

Methods And Materials: Time-kill assays were performed in a control isolate and three MDR-MRSP isolates at six clinically relevant concentrations [32 to 1,024 × MIC (the minimum inhibitory concentration)]. Whole-genome resequencing and bioinformatic analysis were performed in the resistant strains developed in this assay.

Results: The genomic analysis identified nine antimicrobial resistance genes (ARGs) in MDR-MRSP isolates, which are responsible for resistance to seven classes of antibiotics. RFP activity against all four isolates was consistent with a time-dependent and bacteriostatic response. RFP resistance was observed in six of the 28 time-kill assays, including concentrations 64 × MIC in MDR-MRSP1 isolates at 24 h, 32 × MIC in MDR-MRSP2 at 48 h, 32 × MIC in MDR-MRSP3 at 48 h and 256 × MIC in MDR-MRSP3 at 24 h. Genome-wide mutation analyses in these RFP-resistant strains discovered the causal mutations in the coding region of the rpoB gene.

Conclusions And Clinical Relevance: A study has shown that 6 mg/kg per os results in plasma concentrations of 600-1,000 × MIC of S. pseudintermedius. Based on our data, this dose should achieve the minimum MIC (×512) to prevent RFP resistance development; therefore, we recommend a minimum daily dose of 6 mg/kg for MDR-MRSP pyoderma treatment when limited antibiotic options are available.
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http://dx.doi.org/10.1111/vde.12959DOI Listing
June 2021

The chromosome-level genome of dragon fruit reveals whole-genome duplication and chromosomal co-localization of betacyanin biosynthetic genes.

Hortic Res 2021 Mar 10;8(1):63. Epub 2021 Mar 10.

Nebraska Food for Health Center, Department of Food Science and Technology, University of Nebraska, Lincoln, NE, 68588, USA.

Dragon fruits are tropical fruits economically important for agricultural industries. As members of the family of Cactaceae, they have evolved to adapt to the arid environment. Here we report the draft genome of Hylocereus undatus, commercially known as the white-fleshed dragon fruit. The chromosomal level genome assembly contains 11 longest scaffolds corresponding to the 11 chromosomes of H. undatus. Genome annotation of H. undatus found ~29,000 protein-coding genes, similar to Carnegiea gigantea (saguaro). Whole-genome duplication (WGD) analysis revealed a WGD event in the last common ancestor of Cactaceae followed by extensive genome rearrangements. The divergence time between H. undatus and C. gigantea was estimated to be 9.18 MYA. Functional enrichment analysis of orthologous gene clusters (OGCs) in six Cactaceae plants found significantly enriched OGCs in drought resistance. Fruit flavor-related functions were overrepresented in OGCs that are significantly expanded in H. undatus. The H. undatus draft genome also enabled the discovery of carbohydrate and plant cell wall-related functional enrichment in dragon fruits treated with trypsin for a longer storage time. Lastly, genes of the betacyanin (a red-violet pigment and antioxidant with a very high concentration in dragon fruits) biosynthetic pathway were found to be co-localized on a 12 Mb region of one chromosome. The consequence may be a higher efficiency of betacyanin biosynthesis, which will need experimental validation in the future. The H. undatus draft genome will be a great resource to study various cactus plants.
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http://dx.doi.org/10.1038/s41438-021-00501-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943767PMC
March 2021

Unification and extensive diversification of M/Orf3-related ion channel proteins in coronaviruses and other nidoviruses.

Virus Evol 2021 Jan 16;7(1):veab014. Epub 2021 Feb 16.

Department of Biology, College of Arts and Sciences, Saint Louis University, St. Louis, MO 63103, USA.

The coronavirus, Severe Acute Respiratory Syndrome (SARS)-CoV-2, responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic, has emphasized the need for a better understanding of the evolution of virus-host interactions. ORF3a in both SARS-CoV-1 and SARS-CoV-2 are ion channels (viroporins) implicated in virion assembly and membrane budding. Using sensitive profile-based homology detection methods, we unify the SARS-CoV ORF3a family with several families of viral proteins, including ORF5 from MERS-CoVs, proteins from beta-CoVs (ORF3c), alpha-CoVs (ORF3b), most importantly, the Matrix (M) proteins from CoVs, and more distant homologs from other nidoviruses. We present computational evidence that these viral families might utilize specific conserved polar residues to constitute an aqueous pore within the membrane-spanning region. We reconstruct an evolutionary history of these families and objectively establish the common origin of the M proteins of CoVs and Toroviruses. We also show that the divergent ORF3 clade (ORF3a/ORF3b/ORF3c/ORF5 families) represents a duplication stemming from the M protein in alpha- and beta-CoVs. By phyletic profiling of major structural components of primary nidoviruses, we present a hypothesis for their role in virion assembly of CoVs, ToroVs, and Arteriviruses. The unification of diverse M/ORF3 ion channel families in a wide range of nidoviruses, especially the typical M protein in CoVs, reveal a conserved, previously under-appreciated role of ion channels in virion assembly and membrane budding. We show that M and ORF3 are under different evolutionary pressures; in contrast to the slow evolution of M as core structural component, the ORF3 clade is under selection for diversification, which suggests it might act at the interface with host molecules and/or immune attack.
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http://dx.doi.org/10.1093/ve/veab014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928690PMC
January 2021

Profiling of the assembly of RecA nucleofilaments implies a potential target for environmental factors to disturb DNA repair.

J Environ Sci (China) 2021 Apr 13;102:283-290. Epub 2020 Oct 13.

Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China; Institute of Environment and Health, Jianghan University, Wuhan 430056, China; Institute of Environment and Health, Hangzhou Institute for Advanced Study, UCAS, Hangzhou 430056, China. Electronic address:

Double-strand breaks (DSBs), one class of the most harmful DNA damage forms that bring elevated health risks, need to be repaired timely and effectively. However, an increasing number of environmental pollutants have been identified to impair DSB repair from various mechanisms. Our previous work indicated that the formation of unsaturated RecA nucleofilaments plays an essential role in homology recombination (HR) pathway which can accurately repair DSBs. In this study, by developing a benzonase cutting protection assay and combining it with traditional electrophoretic mobility shift assay (EMSA) analysis, we further investigated the assembly patterns of four RecA mutants that display differential DSB repair ability and ATPase activity. We observed that the mutants (G204S and S69G) possessing both ATP hydrolysis and DSB repair activities form unsaturated nucleofilaments similar to that formed by the wild type RecA, whereas the other two ATP hydrolysis-deficient mutants (K72R and E96D) that fail to mediate HR form more compacted nucleofilaments in the presence of ATP. These results establish a coupling of ATPase activity and effective DSB repair ability via the assembly status of RecA nucleofilaments. This linkage provides a potential target for environmental factors to disturb the essential HR pathway for DSB repair by suppressing the ATPase activity and altering the assembly pattern of nucleofilaments.
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http://dx.doi.org/10.1016/j.jes.2020.09.022DOI Listing
April 2021

Sex-seeking on the internet and mobile-based applications among young people in China: An online survey.

Int J STD AIDS 2021 04 20;32(5):403-410. Epub 2021 Feb 20.

National Center for AIDS/STD Control and Prevention196543, Chinese Center for Disease Control and Prevention, Beijing, China.

The aim of this study was to investigate young people's risk behaviors in use of social network applications for sexual purposes. Snowball sampling technique was used to recruit participants online. Logistic regressions were performed to examine interrelationships among risk behaviors and sex-seeking platforms (A, B, C, D, and others). The prevalence of online sex-seeking was 22.2% (1156/5199) among people with sexual experience, and the most debut online sex-seeking happened in 15-24 years old in both men and women (79.8%, 590/739 vs 86.1%, 359/417). The risk behaviors varied in different platforms among 730 young people age 15-24 years. Among men, participants seeking sex via B were more likely to engage in concurrent sexual partnership (aOR: 1.64; 95% CI: 1.01-2.66). Participants seeking sex via C were more likely to engage in drug use (aOR: 1.74; 95% CI: 1.01-3.02) and condomless sex (aOR: 1.75; 95% CI: 1.04-2.95). Participants seeking sex via A, C, or D were all less likely to have homosexual behaviors. Among women, participants seeking sex via B were more likely to have condomless sex (aOR: 2.06; 95% CI: 1.10-3.86). The study indicated that emerging of the HIV epidemic in young people might be driven by risk behaviors during online sex-seeking. Effective intervention programs need to target on different social network platforms.
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http://dx.doi.org/10.1177/0956462420971940DOI Listing
April 2021

Effectiveness of Single Nucleotide Polymorphism Markers in Genotyping Germplasm Collections of Using KASP Assay.

Front Plant Sci 2020 25;11:612593. Epub 2021 Jan 25.

Sustainable Perennial Crops Laboratory, Agricultural Research Service, United States Department of Agriculture, Beltsville, MD, United States.

Accurate genotype identification is imperative for effective use of L. germplasm to breed new varieties with tolerance or resistance to biotic and abiotic stresses (including moisture stress and pest and disease stresses such as coffee berry borer and rust) and for high yield and improved cup quality. The present study validated 192 published single nucleotide polymorphism (SNP) markers and selected a panel of 120 loci to examine parentage and labeling errors, genetic diversity, and population structure in 400 accessions assembled from different coffee-producing countries and planted in a field gene bank in Ghana. Of the 400 genotypes analyzed, both synonymous (trees with same SNP profiles but different names, 12.8%) and homonymous (trees with same name but different SNP profiles, 5.8%) mislabeling were identified. Parentage analysis showed that 33.3% of the progenies derived from controlled crossing and 0% of the progenies derived from an open pollinated biclonal seed garden had parentage (both parents) corresponding to breeder records. The results suggest mislabeling of the mother trees used in seed gardens and pollen contamination from unwanted paternal parents. After removing the duplicated accessions, Bayesian clustering analysis partitioned the 270 unique genotypes into two main populations. Analysis of molecular variance (AMOVA) showed that the between-population variation accounts for 41% of the total molecular variation and the genetic divergence was highly significant (st = 0.256; < 0.001). Taken together, our results demonstrate the effectiveness of using the selected SNP panel in gene bank management, varietal identification, seed garden management, nursery verification, and coffee bean authentication for breeding programs.
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http://dx.doi.org/10.3389/fpls.2020.612593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868401PMC
January 2021

Probing sulfatide-tissue lectin recognition with functionalized glycodendrimersomes.

iScience 2021 Jan 10;24(1):101919. Epub 2020 Dec 10.

Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich, Veterinärstr. 13, 80539 Munich, Germany.

The small 3--sulfated galactose head group of sulfatides, an abundant glycosphingolipid class, poses the (sphinx-like) riddle on involvement of glycan bridging by tissue lectins (sugar code). First, synthesis of head group derivatives for functionalization of amphiphilic dendrimers is performed. Aggregation of resulting (biomimetic) vesicles, alone or in combination with lactose, demonstrates bridging by a tissue lectin (galectin-4). Physiologically, this can stabilize glycolipid-rich microdomains (rafts) and associate sulfatide-rich regions with specific glycoproteins. Further testing documents importance of heterobivalency and linker length. Structurally, sulfatide recognition by galectin-8 is shown to involve sphingosine's OH group as substitute for the 3'-hydroxyl of glucose of lactose. These discoveries underscore functionality of this small determinant on biomembranes intracellularly and on the cell surface. Moreover, they provide a role model to examine counterreceptor capacity of more complex glycans of glycosphingolipids and to start their bottom-up glycotope surface programming.
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http://dx.doi.org/10.1016/j.isci.2020.101919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773886PMC
January 2021

Accurate Differentiation of Green Beans of Arabica and Robusta Coffee Using Nanofluidic Array of Single Nucleotide Polymorphism (SNP) Markers.

J AOAC Int 2020 Apr;103(2):315-324

Sustainable Perennial Crops Laboratory, USDA, Agricultural Research Service, Beltsville, MD 20705, USA.

Green (unroasted) coffee is one of the most traded agricultural commodities in the world. The Arabica (Coffea arabica L.) and Robusta (Coffea canephora Pierre ex A. Froehner) species are the two main types of coffees for commercial production. In general, Arabica coffee is known to have better quality in terms of sensory characteristics; thus, it has a higher market value than Robusta coffee. Accurate differentiation of green beans of the two species is, therefore, of commercial interest in the coffee industry. Using the newly developed single nucleotide polymorphism (SNP) markers, we analyzed a total of 80 single green bean samples, representing 20 Arabica cultivars and four Robusta accessions. Reliable SNP fingerprints were generated for all tested samples. Unambiguous differentiation between Robusta and Arabica coffees was achieved using multivariate analysis and assignment test. The SNP marker panel and the genotyping protocol are sufficiently robust to detect admixture of green coffee in a high-throughput fashion. Moreover, the multilocus SNP approach can differentiate every single bean within Robusta and 55% of Arabica samples. This advantage, together with the single-bean sensitivity, suggests a significant potential for practical application of this technology in the coffee industry.
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http://dx.doi.org/10.1093/jaocint/qsz002DOI Listing
April 2020

An electroosmotic flow-free two-direction migration strategy enables fast affinity capillary electrophoresis to study the weak interactions between basic peptides and RNA.

Anal Methods 2020 12;12(48):5833-5838

The State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

Affinity Capillary Electrophoresis (ACE) is a useful analytical tool to study noncovalent interactions. However, it remains challenging for ACE to measure weak and unstable interactions due to the fast dissociation of the binding complex and the possible destruction of the complex by a high electric field. In this study, we proposed a two-direction migration strategy that enables ACE to detect weak and unstable but important interactions by decreasing the migration distance of the binding complex and controlling the opposite migration direction of the free probe. By synthesizing a polyacrylamide-coated neutral capillary, free of electroosmotic flow, two-direction CE migration of basic peptides (positively charged) and peptide-RNA complexes (negatively charged) was achieved. Furthermore, the weak interactions between small nuclear U2 RNA and histone peptides were detected by this two-direction migration CE approach. The effects of the methylation states of histone peptides on the weak peptide-RNA interactions were also explored by this new approach. Collectively, the suggested modification of the ACE method is able to qualitatively characterize weak interactions.
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http://dx.doi.org/10.1039/d0ay01515fDOI Listing
December 2020

Unification of the M/ORF3-related proteins points to a diversified role for ion conductance in pathogenesis of coronaviruses and other nidoviruses.

bioRxiv 2020 Nov 11. Epub 2020 Nov 11.

The new coronavirus, SARS-CoV-2, responsible for the COVID-19 pandemic has emphasized the need for a better understanding of the evolution of virus-host conflicts. ORF3a in both SARS-CoV-1 and SARS-CoV-2 are ion channels (viroporins) and involved in virion assembly and membrane budding. Using sensitive profile-based homology detection methods, we unify the SARS-CoV ORF3a family with several families of viral proteins, including ORF5 from MERS-CoVs, proteins from beta-CoVs (ORF3c), alpha-CoVs (ORF3b), most importantly, the Matrix (M) proteins from CoVs, and more distant homologs from other nidoviruses. By sequence analysis and structural modeling, we show that these viral families utilize specific conserved polar residues to constitute an ion-conducting pore in the membrane. We reconstruct the evolutionary history of these families, objectively establish the common origin of the M proteins of CoVs and Toroviruses. We show that the divergent ORF3a/ORF3b/ORF5 families represent a duplication stemming from the M protein in alpha- and beta-CoVs. By phyletic profiling of major structural components of primary nidoviruses, we present a model for their role in virion assembly of CoVs, ToroVs and Arteriviruses. The unification of diverse M/ORF3 ion channel families in a wide range of nidoviruses, especially the typical M protein in CoVs, reveal a conserved, previously under-appreciated role of ion channels in virion assembly, membrane fusion and budding. We show that the M and ORF3 are under differential evolutionary pressures; in contrast to the slow evolution of M as core structural component, the CoV-ORF3 clade is under selection for diversification, which indicates it is likely at the interface with host molecules and/or immune attack.

Importance: Coronaviruses (CoVs) have become a major threat to human welfare as the causative agents of several severe infectious diseases, namely Severe Acute Respiratory Syndrome (SARS), Middle Eastern Respiratory Syndrome (MERS), and the recently emerging human coronavirus disease 2019 (COVID-19). The rapid spread, severity of these diseases, as well as the potential re-emergence of other CoV-associated diseases have imposed a strong need for a thorough understanding of function and evolution of these CoVs. By utilizing robust domain-centric computational strategies, we have established homologous relationships between many divergent families of CoV proteins, including SARS-CoV/SARS-CoV-2 ORF3a, MERS-CoV ORF5, proteins from both beta-CoVs (ORF3c) and alpha-CoVs (ORF3b), the typical CoV Matrix proteins, and many distant homologs from other nidoviruses. We present evidence that they are active ion channel proteins, and the Cov-specific ORF3 clade proteins are under selection for rapid diversification, suggesting they might have been involved in interfering host molecules and/or immune attack.
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http://dx.doi.org/10.1101/2020.11.10.377366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668736PMC
November 2020

Comparative analysis reveals the expansion of mitochondrial DNA control region containing unusually high G-C tandem repeat arrays in Nasonia vitripennis.

Int J Biol Macromol 2021 Jan 4;166:1246-1257. Epub 2020 Nov 4.

Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, United States of America; HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, United States of America; Alabama Agricultural Experiment Station, Auburn University, Auburn, AL 36849, United States of America; Department of Entomology and Plant Pathology, Auburn University, Auburn, AL 36849, United States of America. Electronic address:

Insect mitochondrial DNA (mtDNA) ranges from 14 to 19 kbp, and the size difference is attributed to the AT-rich control region. Jewel wasps have a parasitoid lifestyle, which may affect mitochondria function and evolution. We sequenced, assembled, and annotated mitochondrial genomes in Nasonia and outgroup species. Gene composition and order are conserved within Nasonia, but they differ from other parasitoids by two large inversion events that were not reported before. We observed a much higher substitution rate relative to the nuclear genome and mitochondrial introgression between N. giraulti and N. oneida, which is consistent with previous studies. Most strikingly, N. vitripennis mtDNA has an extremely long control region (7665 bp), containing twenty-nine 217 bp tandem repeats and can fold into a super-cruciform structure. In contrast to tandem repeats commonly found in other mitochondria, these high-copy repeats are highly conserved (98.7% sequence identity), much longer in length (approximately 8 Kb), extremely GC-rich (50.7%), and CpG-rich (percent CpG 19.4% vs. 1.1% in coding region), resulting in a 23 kbp mtDNA beyond the typical size range in insects. These N. vitripennis-specific mitochondrial repeats are not related to any known sequences in insect mitochondria. Their evolutionary origin and functional consequences warrant further investigations.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.11.007DOI Listing
January 2021

Elevated temperature and drought stress significantly affect fruit quality and activity of anthocyanin-related enzymes in jujube (Ziziphus jujuba Mill. cv. 'Lingwuchangzao').

PLoS One 2020 5;15(11):e0241491. Epub 2020 Nov 5.

School of Agriculture, Ningxia University, Yinchuan, Ningxia, China.

The quality attributes of jujube fruit can be directly and indirectly affected by abiotic stresses associated with climate change. Increased temperature and drought are among the most important factors challenging sustainable jujube production in the temperate semi-arid region in northwest China. The main objective of the present study was to understand the effects of elevated air temperature and drought stress on sugar and acid accumulation and coloration of jujube fruits. The content of soluble sugar, organic acid and pigments of traditional jujube "Linwuchangzao" under different atmospheric temperatures and drought stresses were analyzed during three different fruit ripening stages. The elevated temperature (1.5-2.5° C than normal temperature) significantly increased the fruit sugar content, sugar-acid ratio, anthocyanins, flavonoids and carotenoids content. Under the drought stress where the soil moisture was 30% -50% of the field capacity, sugar content, anthocyanin, flavonoid and carotenoid content of the fruit were significantly reduced at the same temperature, but the chlorophyll and organic acid content increased. No significant interaction of Temperature x Drought was observed for all the analyzed quality parameters. The current results showed that the fruit quality of jujube variety "Lingwuchangzao" could be improved when the atmospheric temperature increases by 2° C in this region. However, drought stress had a negative impact on the fruit's sugar-acid ratio and pigment content. The present results also showed that the synthesis and accumulation of anthocyanins in jujube fruit were positively correlated with sugar content and related enzyme activities, especially Phenylalanine Ammonia-lyase (PAL) activity. This study, therefore, provides novel information for understanding the influence of growth environment on the quality properties of jujube fruits. This knowledge will help develop appropriate crop management practices for jujube production in arid and semi-arid areas in northwest China.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241491PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646374PMC
December 2020

Design of a multi-modality DMD-based two-photon microscope system.

Opt Express 2020 Sep;28(20):30187-30198

We present the modular design and characterization of a multi-modality video-rate two-photon excitation (TPE) microscope based on integrating a digital micromirror device (DMD), which functions as an ultrafast beam shaper and random-access scanner, with a pair of galvanometric scanners. The TPE microscope system realizes a suite of new imaging functionalities, including (1) multi-layer imaging with 3D programmable imaging planes, (2) DMD-based wavefront correction, and (3) multi-focus optical stimulation (up to 22.7 kHz) with simultaneous TPE imaging, all in real-time. We also report the detailed optomechanical design and software development that achieves high level system automation. To verify the performance of different microscope functions, we have devised and performed imaging experiments on Drosophila brain, mouse kidney and human stem cells. The results not only show improved imaging resolution and depths via the DMD-based adaptive optics, but also demonstrate fast multi-focus stimulation for the first time. With the new imaging capabilities, e.g., tools for optogenetics, the multi-modality TPE microscope may play a critical role in the applications pertinent to neuroscience and biophotonics.
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http://dx.doi.org/10.1364/OE.404652DOI Listing
September 2020

Dietary fats suppress the peritoneal seeding of colorectal cancer cells through the TLR4/Cxcl10 axis in adipose tissue macrophages.

Signal Transduct Target Ther 2020 10 15;5(1):239. Epub 2020 Oct 15.

Department of Biochemistry and Molecular Biology, Third Military Medical University (Army Medical University), 400038, Chongqing, China.

Peritoneal carcinomatosis (PC) of colorectal cancer (CRC) is a terminal phase of malignancy with no effective strategies for the prevention of this condition. Here we established PC models in mice by intraperitoneal engraftment of CRC cells and revealed an unexpected role for a high-fat diet (HFD) in preventing metastatic seeding in the visceral fat. Mechanistically, the HFD stimulated the activation of adipose tissue macrophages (ATMs) toward an M1-like phenotype and enhanced ATM tumor phagocytosis in a TLR4-dependent manner. Furthermore, the TLR4-Cxcl10 axis in ATMs promoted T cell recruitment, and M1-like macrophages stimulated T cell activation in tumor-seeded fats. The inhibitory effect of the HFD on tumor seeding was abolished with the ablation of macrophages, inactivation of T cells, or blockade of the TLR4-Cxcl10 axis in macrophages. Finally, we showed that a HFD and conventional chemotherapeutic agents (oxaliplatin or 5-fluorouracil) synergistically improved the survival of tumor-seeded mice. Collectively, our findings demonstrate that peritoneal seeding of CRC can be suppressed by short-term treatment with a HFD in the early phase, providing a novel concept for the management of these patients in the clinic.
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http://dx.doi.org/10.1038/s41392-020-00327-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566605PMC
October 2020
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