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1. chinaXiv:202101.00036 [pdf]

Targeting pan-tumor antigens to activating Fcγ receptors generates a novel dendritic cell tumor vaccine

Sheng, Hui; Wnag, Pan; Zhang, Guoxiu; Zhang, Xiao; Li, Zhongjun; Zhao, Zhihui
Subjects: Medicine, Pharmacy >> Preclinical Medicine

Objective: Therapeutic tumor vaccines are eagerly awaited in clinic by patients with high expectations; however, very few clinically successful tumor vaccine has been developed thus far, and there remains no consensus on the generation of tumor vaccines. We hypothesized that targeted delivery of pan-tumor antigens instead of individual tumor-associated antigen (TAA) to dendritic cells via the activating receptor endocytic pathway (AREP) would provide an alternative avenue to develop potent personalized tumor vaccines. Methods: We first prepared biotin-tagged tumor antigens (B-TAgs) with mouse CT26. WT colorectal cancer cells by exploiting metabolic glycan labeling and bioorthogonal reaction methods; then, we prepared a bifunctional fusion protein containing streptavidin and a mouse IgG2a Fc fragment (SA-Fc), in which streptavidin was used for conjugation with B-TAgs, and Fc for mediating the interaction with the Fcγ receptor. Finally, conjugates (Fc-TAgs) of SA-Fc with B-TAgs were prepared based on affinity-guided noncovalent reaction. The phenotype of Fc-TAgs pulsed bone marrow-derived dendritic cells (BMDCs) was examined by flow cytometry. The therapeutic effects of Fc-TAgs pulsed BMDCs were observed in an established mouse CT26. WT colorectal cancer model. Results: The prepared B-TAgs covers almost all glycosylated tumor antigens. SA-Fc fusion protein exhibits biotin-binding activity as a homodimer. SA-Fc can effectively conjugate with B-TAg at a mixing ratio of 1:96 (w/w). Data of flow cytometry revealed that on Fc-TAgs pulsed BMDCs, the expression levels of surface molecules, such as CD80 and MHC II, were greatly increased. In the established murine colorectal cancer model, combination treatments with Fc-TAgs pulsed BMDCs and PD-1 blockade achieved significant therapeutic effects. Limitations: The strategy we proposed for the preparation of personalized tumor vaccine requires that the tumor be surgically removed from the patient. The rationality and validity of this strategy need to be proven by more preclinical investigations. Conclusions: The novel strategy we proposed circumvents the necessities for neoantigen prediction and provides an alternative pathway to establish a flexible system for the preparation of personalized dendritic cell tumor vaccines. In the setting of checkpoint blockade-based immunotherapy, a novel DCV would improve antitumor immunity and benefit the eradication of tumor residues within the body of the cancer patients.

submitted time 2021-01-07 Hits1728Downloads234 Comment 0

2. chinaXiv:202004.00001 [pdf]

Reappraisal of Serridentinus gobiensis Osborn & Granger?and Miomastodon tongxinensis Chen:the validity of Miomastodon

WANG Shi-Qi; ZHANG Xiao-Xiao; LI Chun-Xiao?
Subjects: Biology >> Zoology

The elephantimorph proboscideans, Serridentinus gobiensis Osborn & Granger, 1932, and Miomastodon tongxinensis Chen, 1978, from the Middle Miocene of northern China, were revised as Zygolophodon gobiensis (Osborn & Granger, 1932). However, their phylogenetic positions are still being debated because of their intermediate morphology between the typical bunodont (Gomphotheriidae) and zygodont (Mammutidae) elephantimorphs. In the present paper, we compare their dental and mandibular morphology with that of the Eurasian Z. turicensis, Gomphotherium subtapiroideum, and G. tassyi, as well as the North American Mio. merriami and G. productum. It appears that S. gobiensis and Mio. tongxinensis share with Mio. merriami the slightly more bunodont molar morphology than that of Z. turicensis, e.g., the thicker enamel, thicker pretrite crescentoids, higher interlophid enamel pillars in buccal view, and the narrower contour majorly caused by the narrower posttrite half loph(id)s. S. gobiensis and Mio. merriami also possess an “erected oval cross-sectioned mandibular tusk”, in which the cross-section is mediolaterally compressed (dorsoventral diameter being larger than the mediolateral one). Whereas, in Z. turicensis and G. productum, the mandibular tusk is “laid oval cross-sectioned”, in which the cross-section is dorsoventrally compressed (dorsoventral diameter is smaller than the mediolateral one). Therefore, it is reasonable to revive the genus Miomastodon Osborn, 1922, which contains the species that were previously attributed to Zygolophodon, but they have relatively bunodont molar morphology (i.e., the robust type of the Z. turicensis group). The mandibular tusk with erected?oval cross-section seems to be a synapomorphy of Miomastodon species. Furthermore, the molar morphology of G. subtapiroideum and G. tassyi also exhibits intermediate status between the typical bunodonts and zygodonts. However, the mandibular symphysis of G. subtapiroideum and G. tassyi is stronger than that of Miomastodon, and the mandibular tusk is pyriform cross-sectioned. The validity of Miomastodon and G. subtapiroideum/tassyi obscures the boundary between the Gomphotheriidae and Mammutidae, and suggests that the evolutions of the Gomphotheriidae and?Mammutidae are deeply involved in with each other, rather than straightforwardly detached. This phenomenon has been revealed by a collagen sequence analysis among Notiomastodon, Mammut, and extant elephants, which should be further studied.

submitted time 2020-03-31 From cooperative journals:《古脊椎动物学报》 Hits6334Downloads1002 Comment 0

3. chinaXiv:201910.00052 [pdf]

Effects of temperature on flowering phenological traits of Populus euphratica Oliv. and Populus pruinosa Schrenk populations, Xinjiang, China

LI Zhijun; ZHANG Xiao; ZHENG Yaqiong; QIU Aijun; ZHANG Ling
Subjects: Environmental Sciences, Resource Sciences >> Basic Disciplines of Environmental Science and Technology

The aims of this study were to explore the interspecific differences of Populus euphratica Oliv. and Populus pruinosa Schrenk populations and the intraspecific differences of males and females within the same species in flowering phenological traits, and the effects of temperatures on flowering phenological traits in different growth years (2001–2003 and 2013–2015). The results showed that P. euphratica population flowered earlier than P. pruinosa population. Moreover, flowering phenological period of population, number of days of flowering phenological period per population, number of days of flowering phenological period per plant and average number of days of flowering period per plant of P. euphratica population were less than those of P. pruinosa population. The differences between male and female within the same species indicated that the flowering periods of males P. euphratica and P. pruinosa populations were earlier than those of female plants. For both species, flowering phenological traits were significantly and negatively correlated with the average temperatures in previous ten days, previous one month and previous three months of flowering. Both species are sensitive to temperature changes and adjust to the changes by advancing the start of flowering and prolonging the duration of flowering.

submitted time 2019-10-26 From cooperative journals:《Journal of Arid Land》 Hits4474Downloads560 Comment 0

4. chinaXiv:201711.00147 [pdf]

Probing Diverse Disulfur Ligands in the Mo2Sn–/0 (n = 4 ~ 8) Clusters: Structural Evolution and Chemical Bonding

ZHANG Xiao-Fei; LIU Xiu-Juan; XU Ruo-Nan; WU Ni; HUANG Xin; WANG Bin
Subjects: Chemistry >> Physical Chemistry

Density functional theory (DFT) and coupled cluster theory (CCSD(T)) calculations were employed to investigate the geometric and electronic structures of a range of dinuclear molybdenum sulfide clusters, Mo2Sn– and Mo2Sn (n = 4~8). The results showed that the sulfur atoms tended to occupy the terminal sites of the clusters continuously in the process of sequential sulfidation. After the oxidation state of Mo atoms reached the maximum of +6, diverse disulfur ligands emerged in the sulfur-rich Mo2Sn–/0 (n = 7, 8) clusters. The driving forces of removing a sulfur atom from different S ligands in Mo2Sn–/0 (n = 4~8) clusters, especially from those disulfur units, were evaluated. The corresponding order may provide insight into the pretreatment of fresh MoS2 catalysts. Vertical detachment energies (VDEs) were predicted according to the Generalized Koopmans’ theorem, and then the photoelectron spectra (PES) were simulated. Molecular orbital and spin density values were analyzed to elucidate the chemical bonding and the evolutionary behavior in the dinuclear molybdenum sulfide clusters.

submitted time 2017-11-05 From cooperative journals:《结构化学》 Hits781Downloads452 Comment 0

5. chinaXiv:201605.01400 [pdf]

Core component EccB1 of the Mycobacterium tuberculosis type VII secretion system is a periplasmic ATPase

Zhang, Xiao-Li; Zhang, Xian-En; Zhang, Xiao-Li; Li, De-Feng; Fleming, Joy; Wang, Li-Wei; Zhou, Ying; Wang, Da-Cheng; Zhang, Xian-En; Bi, Li-Jun; Zhang, Xiao-Li; Li, De-Feng; Fleming, Joy; Wang, Li-Wei; Zhou, Ying; Wang, Da-Cheng; Zhang, Xian-En; Bi, Li-Jun; Zhang, Xiao-Li
Subjects: Biology >> Biophysics >> Biochemistry & Molecular Biology

Pathogenic mycobacteria transport virulence factors across their complex cell wall via a type VII secretion system (T7SS)/early secreted antigenic target-6 of kDa secretion system (ESX). ESX conserved component (Ecc) B, a core component of the T7SS architecture, is predicted to be a membrane bound protein, but little is known about its structure and function. Here, we characterize EccB1, showing that it is an ATPase with no sequence or structural homology to other ATPases located in the cell envelope of Mycobacterium tuberculosis H37Rv. We obtained the crystal structure of an EccB1-DN72 truncated transmembrane helix and performed modeling and ATP docking studies, showing that EccB1 likely exists as a hexamer. Sequence alignment and ATPase activity determination of EccB1 homologues indicated the presence of 3 conserved motifs in the N- and C-terminals of EccB1-DN72 that assemble together between 2 membrane proximal domains of the EccB1-DN72 monomer. Models of the EccB1 hexamer show that 2 of the conserved motifs are involved in ATPase activity and form an ATP binding pocket located on the surface of 2 adjacent molecules. Our results suggest that EccB may act as the energy provider in the transport of T7SS virulence factors and may be involved in the formation of a channel across the mycomembrane.

submitted time 2016-05-12 Hits1486Downloads917 Comment 0

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